bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–04–19
57 papers selected by
Luca Bolliger, lxBio



  1. Expert Rev Anti Infect Ther. 2026 Apr 14. 1-4
      
    Keywords:  Bacteriophage; antibody; immune responses; inflammation; phage therapy
    DOI:  https://doi.org/10.1080/14787210.2026.2659723
  2. Front Microbiol. 2026 ;17 1748742
      The rapid rise of multidrug-resistant and extensively drug-resistant bacterial infections has renewed interest in bacteriophages as adaptable, targeted antimicrobials. Recent advances in phage engineering, including CRISPR-based approaches, now make it possible to refine host range, strengthen lytic performance, and deliver genetic payloads that target clinically important resistance determinants such as blaNDM, mecA, and mcr-1. In parallel, jumbo phages with large genomes often encode additional functions that support replication and biofilm disruption, offering practical advantages in densely structured infections where antibiotics perform poorly. A second limitation in phage translation has been measurement: in most settings, dosing and treatment duration remain guided by indirect endpoints rather than real-time information on distribution and activity. Near-infrared bioimaging addresses this gap by enabling noninvasive tracking of infection burden and phage kinetics in vivo through bacteriophytochrome-derived reporters, including iRFPs, miRFPs, and PAiRFPs. In this review, we bring these developments together and discuss how CRISPR-enabled phage engineering, jumbo-phage biology, and near-infrared readouts can be integrated into a precision framework that is measurable, adaptable, and clinically interpretable. We examine evidence across major drug-resistant pathogens, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Burkholderia cepacia, and Mycobacterium abscessus. We also summarize practical constraints that remain central to clinical translation, manufacturing quality, host immune neutralization, and regulatory variability, and outline a realistic development pathway in which engineered phages and companion diagnostics progress from animal models to carefully defined clinical indications. Together, these advances support a shift from empirical phage use toward a more standardized, data-driven approach to treating drug-resistant infections.
    Keywords:  CRISPR-engineered bacteriophages; bacteriophage therapy; biofilm disruption; extensively drug-resistant bacteria; jumbo phages; multidrug-resistant bacteria; near-infrared bioimaging; phage pharmacokinetics
    DOI:  https://doi.org/10.3389/fmicb.2026.1748742
  3. Cell Rep. 2026 Apr 16. pii: S2211-1247(26)00353-0. [Epub ahead of print]45(4): 117275
      The high specificity of phages toward their hosts holds great promise for phage therapy while posing a challenge to computational prediction approaches. To this end, we introduce PhageHost (P&H), an ensemble pipeline for large-scale discovery of phage tail fibers and strain-level host prediction in Klebsiella pneumoniae using protein language models (PLMs). The pipeline begins with TailSeek, a PLM for tail fiber detection from phage and prophage genomes. Building on TailSeek predictions, we developed HostBuster, a deep learning framework that integrates tail fiber features with host-specific information to predict the lytic potential of phage-K. pneumoniae pairs. In silico and experimental validations confirm that P&H achieves high sensitivity and precision in both tail fiber identification and host prediction. Moreover, our framework demonstrates strong generalizability, enabling large-scale mining of tail fibers from prophage data across diverse bacterial taxa. P&H significantly accelerates high-throughput phage screening, offering a scalable tool for clinical phage therapy applications.
    Keywords:  CP: microbiology; CP: molecular biology; Klebsiella pneumoniae; host range; phage; protein language model; receptor binding protein; tail fiber
    DOI:  https://doi.org/10.1016/j.celrep.2026.117275
  4. Adv Wound Care (New Rochelle). 2026 Apr 16. 21621918261440437
       SIGNIFICANCE: Chronic wounds represent a growing clinical and economic burden, affecting 1-2% of the global population, with prevalence expected to rise due to aging and increasing rates of diabetes, obesity, and vascular diseases. Wound persistence is often driven by infection and compounded by antimicrobial resistance (AMR), resulting in poor patient outcomes. High prevalence of microbial biofilms, which shield pathogens from immune clearance and promote AMR, further promotes the chronicity of infected wounds.
    RECENT ADVANCES: Adoption of antimicrobial stewardship in wound care is increasing, emphasizing timely diagnosis of infection and pathogen identification to guide treatment and limit unnecessary AMR-driving antibiotic use. However, current diagnostic and therapeutic approaches remain only partially effective, particularly for biofilm-containing wounds. While many antimicrobials exist, their use is constrained by negative impacts on wound healing, limited antibiofilm activity, and insufficient evidence of improved clinical outcome. To address these gaps, recent advances in diagnostics and therapeutics aim to disrupt microbial communities, reduce AMR risk, and accelerate wound healing.
    CRITICAL ISSUES: The treatment of chronic wounds is challenged by AMR, biofilms, and the limited effectiveness of current therapies. Contemporary antimicrobials (e.g., broad-spectrum antibiotics and silver) are linked to AMR development, compounded by biofilms that shield pathogens, limit antimicrobial efficacy, and sustain infection. While alternative treatments with lower AMR risk and greater antibiofilm activity are under investigation, the lack of robust clinical data limits their adoption.
    FUTURE DIRECTIONS: Broader adoption of antimicrobial stewardship and biofilm-targeting sustainable wound care practices are key for combatting AMR and improving patient outcomes.
    Keywords:  antimicrobial resistance; biofilm; chronic wounds; wound infection; wound treatment
    DOI:  https://doi.org/10.1177/21621918261440437
  5. Front Cell Infect Microbiol. 2026 ;16 1774993
       Introduction: Antimicrobial resistance poses a major challenge in the treatment of A. baumannii worldwide, especially Carbapenem-Resistant A. baumannii (CRAB) bloodstream infections.
    Objectives: The objective of this study was to isolate and characterize a CRAB-targeting bacteriophage and to evaluate its therapeutic potential, alone and in combination with polymyxin B.
    Methods: From January 2020 to September 2025, adult patients with A. baumannii bloodstream infection were enrolled. Clinically relevant data were collected. A. baumannii strains were isolated from clinical samples and the phage was isolated from wastewater samples collected from hospital by double-layer agar plate method. The synergistic activity of phage-polymyxin B combination therapy was assessed by checkerboard analysis and time-kill assays. BALB/c mice were infected with a CRAB suspension via tail vein to establish the model and were subsequently treated with the phage and phage-antibiotic combination.
    Results: A total of 50 patients suffered from bloodstream infections caused by Acinetobacter baumannii. Among them, 34 (68%) cases were classified as CRAB. Compared with CSAB, they underwent a longer duration of mechanical ventilation(13.00(6.00,28.00) vs.3.00(2.00,4.00),P =0.019), used more triple therapy(9.41% vs.0%,P=0.041), and had a higher in-hospital mortality(82.35% vs.18.75%,P <0.001). Synergistic antibacterial activity between the phage and colistin B was demonstrated using the checkerboard assay and time-kill curve analysis. In a murine bacteremia model, the vB_AbaP_CV1-antibiotic combination significantly reduced tissue bacterial loads, attenuated inflammatory responses, and ameliorated clinical manifestations. Notably, the combined therapy exhibited superior therapeutic efficacy compared to either monotherapy alone.
    Conclusion: CRAB bloodstream infections are associated with high mortality and poor outcomes. vB_AbaP_CV1 can lyse the CRAB strains. Both phage monotherapy and the phage-colistin B combination exhibited therapeutic efficacy, with the combined regimen yielding the optimal outcome.
    Keywords:  bacteriophages; bloodstream infection; carbapenem-resistant Acinetobacter baumannii; multi-drug resistance; vB_AbaP_CV1
    DOI:  https://doi.org/10.3389/fcimb.2026.1774993
  6. Int J Mol Sci. 2026 Mar 31. pii: 3189. [Epub ahead of print]27(7):
      Chronic non-healing wounds, prevalent in diabetic and vascular diseases, arise from dysregulated chemokine signaling that disrupts angiogenesis, immune coordination, and tissue remodeling. This review synthesizes current knowledge on chemokine biology in wound repair, with a focus on their spatiotemporal regulation across the hemostasis, inflammation, proliferation, and remodeling phases. We detail chemokine classification (CC, CXC, CX3C, and C families), receptor interactions, and downstream pathways, including G protein-dependent and β-arrestin-biased mechanisms. Furthermore, we evaluate emerging therapeutic strategies, including neutralizing antibodies, receptor antagonists, engineered chemokines, and biomaterial-based delivery systems designed to restore chemokine gradient integrity and promote healing. Recent advances in structural biology and protein engineering are highlighted as enabling the design of biased ligands and multi-target inhibitors to overcome chemokine redundancy. The review concludes that precision modulation of chemokine networks offers a promising translational framework to redirect chronic inflammation toward regenerative healing, thereby addressing a significant unmet clinical need in chronic wound management.
    Keywords:  GPCR signaling; angiogenesis; chemokines; chronic wounds; wound healing
    DOI:  https://doi.org/10.3390/ijms27073189
  7. Front Pharmacol. 2026 ;17 1770833
      Alcohol-associated liver disease (ALD), a significant cause of chronic liver disease worldwide, is strongly linked to gut microbiome dysregulation. Heavy alcohol use disrupts the gut bacterial equilibrium and damages the intestinal barrier, making it more permeable to microbial toxins (e.g., endotoxins) that trigger liver inflammation. Many studies have investigated ALD, but no single microbial marker has yet been identified as diagnostic. Results from microbiome studies on this condition have been inconsistent; consequently, scientists are developing new microbiome-based indices and multi-omics approaches to improve their ability to predict diseases. The review evaluates current findings on how disturbances in the gut microbiome and deterioration of the intestinal barrier contribute to the development of ALD. The assessment includes microbiome-based treatments such as probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy. Research indicates that probiotics and FMT treatments may enhance liver function and reduce inflammation in patients with ALD. The studies present conflicting results because researchers used different methods and worked with limited numbers of participants. Bacteriophage therapy exists as an experimental treatment method. The development of personalized microbiome treatments, along with biomarker standardization and solutions to technical and ethical challenges, will enable these strategies to enter medical practice. The review integrates existing knowledge of the gut-liver axis in ALD to demonstrate the clinical potential of microbiome-based treatments while highlighting the need for additional research to enhance treatment outcomes.
    Keywords:  alcohol-associated liver disease (ALD); bacteriophage therapy; biomarkers; fecal microbiota transplantation (FMT); gut microbiome; gut-liver axis; multi-omics analysis; probiotics
    DOI:  https://doi.org/10.3389/fphar.2026.1770833
  8. Front Endocrinol (Lausanne). 2026 ;17 1811595
       Background: Diabetic Foot Ulcers are a serious complication of diabetes, and the clinical treatment is challenging. In this study, network meta-analysis was used to evaluate the effect of different non-drug interventions on Diabetic Foot Ulcer healing and provide evidence to support clinical decision-making.
    Methods: Data sources: 8 databases, including PubMed, Embase, Cochrane, WOS, CNKI, Wanfang Data, CBM, and VIP, were systematically searched. Literature screening: According to the principle of PICOS, two researchers independently screened. Quality evaluation: Two researchers independently used the Cochrane bias risk assessment tool (RoB 2.0) to evaluate the risk of bias. Statistical analysis: by NMA of the random effects model under the framework of frequency.
    Results: A total of 24 randomized controlled trials involving 15 types of interventions were included. The overall quality of the included literature was moderate. The results of NMA showed that Negative Pressure Wound Therapy + Standard Care had the best effect on 12-week healing rate. Compared with Standard Care, Gas Therapy+ Dressing Therapy + Standard Care had the best healing time.
    Conclusion: Negative Pressure Wound Therapy + Standard Care may be more beneficial for improving the 12-week healing rate of Diabetic Foot Ulcer, while Gas Therapy + Dressing Therapy + Standard Care may show potential advantages in shortening healing time. However, these results rely on a limited number of small-sample studies with wide confidence intervals, indicating limited certainty of evidence. Consequently, the SUCRA rankings should be interpreted with caution as they are primarily exploratory; further high-quality RCTs are required to confirm these findings.
    Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251122143.
    Keywords:  diabetic foot ulcer; healing rate; healing time; network meta-analysis; non-pharmacological intervention; nursing; wound care
    DOI:  https://doi.org/10.3389/fendo.2026.1811595
  9. Recent Adv Antiinfect Drug Discov. 2026 Apr 07.
      Antimicrobial resistance (AMR) poses a significant threat to global public health and economic stability, driven by the overuse and misuse of antibiotics in human medicine, veterinary practice, and agriculture. The spread of resistance mechanisms, such as enzymatic degradation, efflux pumps, and horizontal gene transfer, further exacerbates this issue, particularly in low-resource settings. This review aims to summarize the current understanding of antimicrobial resistance, including its molecular mechanisms, global challenges, economic burden, and innovative mitigation strategies such as antimicrobial stewardship, phage therapy, antimicrobial peptides, and CRISPR-based approaches. A comprehensive literature review was conducted using scientific databases such as PubMed, Scopus, and Web of Science to gather recent studies, reviews, and guidelines related to AMR. Relevant data on resistance mechanisms, global trends, clinical implications, and mitigation strategies were synthesized to provide an integrated overview of current challenges and solutions. The review highlights how AMR contributes to increased mortality, prolonged illness, and healthcare costs, while barriers such as limited antibiotic research and diagnostic capacity hinder progress. Integrated approaches, including antimicrobial stewardship, vaccination, phage therapy, and CRISPR-based therapies, are essential to reduce resistance. Additionally, global initiatives like surveillance systems and public awareness campaigns play a vital role in controlling the spread of resistant infections. Addressing AMR requires coordinated global efforts involving stewardship programs, novel therapeutics, education, and surveillance systems. Sustainable action can reduce antibiotic misuse and delay resistance development, securing effective treatments for future generations.
    Keywords:  Antimicrobial resistance; alternative therapies; antimicrobial stewardship programs.; crispr-based techniques; global challenges; resistance mechanisms
    DOI:  https://doi.org/10.2174/0127724344421494251207174255
  10. J Vis Exp. 2026 Mar 24.
      This study establishes a bibliometric and visualization-based protocol to systematically evaluate the research landscape, thematic evolution, and collaboration networks of hydrogel technologies for diabetic foot ulcer (DFU) healing from 2001 to 2024. Publications were retrieved from the Web of Science Core Collection, and analyses were conducted using Bibliometrix, VOSviewer, and CiteSpace to examine publication trends, citation performance, and research frontiers. A total of 403 publications from 48 countries were included, with China, the United States, and India as leading contributors. The results show an exponential rise in research output over the past two decades, reflecting growing interdisciplinary interest in advanced hydrogel systems. Research hotspots have evolved from early studies on hydrogel biocompatibility and moisture retention to innovations such as macrophage polarization, angiogenesis-neurogenesis crosstalk, antimicrobial and smart hydrogels, and green synthesis strategies. Unlike previous narrative reviews, this study introduces a quantitative and visualization-based bibliometric framework that objectively maps global scientific evolution and reveals collaboration patterns and emerging research frontiers. The developed protocol provides a reproducible model for mapping scientific knowledge and guiding future translational and clinical applications in DFU management.
    DOI:  https://doi.org/10.3791/69796
  11. J Appl Microbiol. 2026 Apr 02. pii: lxag091. [Epub ahead of print]137(4):
       AIMS: Salmonella is a foodborne pathogen, and the emergence of antimicrobial-resistant (AMR) strains poses a serious global threat to public health. Instead of conventional antibiotics, alternative antimicrobial strategies such as bacteriophages should be considered in the farm-to-fork chain to prevent Salmonella transmission. This study investigated the viability and antimicrobial potential of six Salmonella-specific bacteriophages, each targeting a distinct serotype, including one jumbo phage (MET P1-082).
    MATERIALS AND METHODS: Phage stability was first evaluated after lyophilization to determine whether the bacteriophages remained viable following this process. In addition, their stability was tested under different conditions of pH (4 and 7), temperature (4, 15, and 25°C), and salinity (0.9% and 10%) at multiple time intervals (1 h, 1 day, and 1 week). Phage titers were determined using the double agar overlay plaque assay. Based on the stability results, the antimicrobial efficacy of the phages was tested against Salmonella in artificially contaminated food matrices, including chicken feed (25°C), chicken meat (4°C), and lettuce (4°C). Reductions in Salmonella counts were quantified on Xylose Lysine Deoxycholate (XLD) agar plates.
    RESULTS: Titers of lyophilized phages showed average decrease of 1.3 log10 PFU mL-1. While most phages retained high stability, only MET P1-082 and MET P1-103 remained viable after 1 week at pH 4 (P < 0.001), despite a noticeable decrease in titer. Among the tested phages, the one targeting S. Kentucky achieved the highest reduction (5 log10 CFU g-1) in chicken feed after 24 h (P < 0.01). On chicken meat, the S. Infantis phage provided a 2.97 log10 CFU g-1 reduction after 24 h, while the S. Hadar phage resulted in a 2.76 log10 CFU g-1 reduction on lettuce after 1 week.
    CONCLUSION: The findings demonstrate that the tested bacteriophages remained stable under tested environmental conditions and effectively reduced at least 1 log10 CFU g-1 of Salmonella load in contaminated chicken feed, meat, and lettuce. These results highlight their potential as practical biocontrol agents in food safety applications.
    Keywords:  antibiotic resistance; biocontrol agent; contamination; food safety; phage therapy
    DOI:  https://doi.org/10.1093/jambio/lxag091
  12. Eng Microbiol. 2026 Mar;6(1): 100252
      The interaction and co-evolution between human gut bacteria and their phages shape the dynamic gut microbiome, exerting a significant impact on human health. However, the underlying mechanisms are largely unexplored. In particular, a bacteria-phage interaction model of the Bacteroidota phylum and the Microviridae phages is lacking, limiting our understanding of their ecological roles in human gut. In this study, we isolated a Bacteroidota-infecting Microviridae phage φHBP1 from human feces. Infection of its host Bacteroides fragilis with φHBP1 drives multiple genomic structural variations, which are correlated with host resistance to φHBP1. In turn, our phage evolution assay in B. fragilis H1 obtained φHBP1 mutants that carry mutations within the capsid and pilot proteins and can reinfect the resistant bacterial population. Together, our findings provide novel insights into an antagonistic co-evolution mechanism between gut phage and bacteria, and hold important implications for diversifying phages through evolution to target resistant bacteria in phage therapy.
    Keywords:  Bacteria-phage interaction; Bacteroidota; Microvirus; Phage evolution
    DOI:  https://doi.org/10.1016/j.engmic.2025.100252
  13. Front Microbiol. 2026 ;17 1770628
      Diarrheagenic Escherichia coli (DEC) is still a prominent cause of diarrheal disease and mortality in children under five, and it continues to be a significant worldwide health concern. This review summarises and analyses recent findings (2015-2025) on the classification, geographic distribution, antimicrobial resistance (AMR) patterns, and emerging treatment options for six principal DEC pathotypes: enterotoxigenic (ETEC), enteropathogenic (EPEC), enteroaggregative (EAEC), Shiga toxin-producing (STEC/EHEC), enteroinvasive (EIEC), and adherent-invasive (AIEC) strains. Across diverse regions, diarrheagenic E. coli remains widespread in low- and middle-income populations. However, the epidemiological landscape is changing, as EAEC increasingly replaces traditional pathotypes in parts of Africa and Asia. Resistance levels to ampicillin and trimethoprim-sulfamethoxazole frequently surpass 50%, and rising resistance to fluoroquinolones, azithromycin, and third-generation cephalosporins is increasingly documented. The expansion of multidrug resistance is driven by various mechanisms, including the production of extended-spectrum β-lactamase (ESBL), the transfer of plasmid-borne resistance genes, the activation of efflux pumps, and the formation of biofilms. Novel interventions, including bacteriophage therapy, ETEC-focused vaccine candidates, anti-virulence agents, and approaches to modulate gut microbiota, are progressing from laboratory research to clinical evaluation. Addressing the AMR threat in DEC will need integrated One Health surveillance strategies and tailored antimicrobial stewardship measures. The current evidence highlights an urgent need for coordinated international action to reduce the clinical and public health burden associated with DEC.
    Keywords:  antimicrobial resistance; pathotypes; phage therapy; public health; vaccine development
    DOI:  https://doi.org/10.3389/fmicb.2026.1770628
  14. Int J Mol Sci. 2026 Mar 28. pii: 3082. [Epub ahead of print]27(7):
      Periodontitis (PD) and atrial fibrillation (AF) are two prevalent chronic conditions with substantial public health burdens worldwide. While traditionally studied separately, increasing evidence reveals a complex interplay between PD and AF, mediated primarily by shared inflammatory and immune mechanisms. Chronic periodontal inflammation can trigger systemic immune activation, leading to atrial structural remodeling, fibrosis, and electrical disturbances that predispose individuals to AF. Observational and longitudinal studies consistently demonstrate a higher incidence and recurrence of AF in patients with moderate to severe PD, independent of established cardiovascular risk factors. Key periodontal pathogens, especially Porphyromonas gingivalis, and altered immune cell profiles are implicated in this association, further supported by genetic analyses revealing common molecular pathways. Mechanistic insights from experimental models highlight the role of inflammation-related atrial fibrosis and immune dysregulation as critical drivers linking oral disease to arrhythmogenesis. Additionally, better oral hygiene practices and periodontal treatment have been associated with a reduced risk of AF, suggesting modifiable intervention potential. This review synthesizes current clinical, epidemiological, molecular, and experimental evidence to elucidate the PD-AF relationship, emphasizing periodontal health as a promising target in cardiovascular disease prevention strategies.
    Keywords:  atrial fibrillation; chronic inflammation; immune response; inflammasome; microbial dysbiosis; periodontitis
    DOI:  https://doi.org/10.3390/ijms27073082
  15. Int Wound J. 2026 Apr;23(4): e70912
      Chronic wounds cause a significant burden to affected patients and to society. Effective and objective diagnostic and monitoring methods are needed in wound care, and artificial intelligence offers one promising alternative. In this study, real-world wound images were used to train a convolutional neural network to automatically segment wound area and wound tissues on an image. The study included altogether 362 images of venous, arterial, vasculitis and pyoderma gangrenosum wounds. The model was based on a convolutional neural network architecture U-Net, and fully supervised learning was utilised during the training phase. Wound area reached a Dice Similarity Coefficient (DSC) of 0.927 and Intersection over Union (IoU) of 0.868 using an augmented dataset with pretraining. Fibrinous exudate and granulation performed fairly well with DSC 0.750 and 0.696, and with IoU 0.659 and 0.601, respectively. Necrosis present in only 56 images achieved lower performance with DSC 0.503 and IoU 0.502. In conclusion, this study suggested that it is possible to train a neural network to perform well with images taken for purely clinical purposes. Besides wound area, several wound structures can be identified, but wound structure identification performance is dependent on the number of images featuring the structure.
    Keywords:  artificial intelligence; computer; leg ulcer; neural networks; supervised machine learning; wound healing
    DOI:  https://doi.org/10.1111/iwj.70912
  16. Diagnostics (Basel). 2026 Apr 01. pii: 1053. [Epub ahead of print]16(7):
      Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients-often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics-are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). These pathogens are associated with mortality exceeding 40%, prolonged ICU stays, and increased healthcare costs. Therapeutic advances have reshaped management in recent years. New β-lactam/β-lactamase inhibitor combinations-ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and sulbactam-durlobactam-along with cefiderocol, have provided safer and more effective alternatives to previously used regimens. Yet, none are universally effective, particularly against carbapenemase-producing organisms, especially metallo-β-lactamase (MBL) producers, and resistance may still emerge during treatment. Rapid molecular and phenotypic diagnostics, when integrated into antimicrobial stewardship, have improved early therapy alignment and reduced unnecessary broad-spectrum use. Beyond antibiotics, colonization surveillance and infection control remain pivotal, as colonization often precedes invasive infection. Biofilm formation on devices such as endotracheal tubes and catheters further promotes persistence and relapse. Strategies targeting biofilm disruption, improved dosing guided by pharmacokinetic/pharmacodynamic optimization, and therapeutic drug monitoring are crucial in ICU practice. The future of managing these infections will depend on integrating precision tools-rapid diagnostics, mechanism-based therapy, and stewardship-guided decisions-with emerging treatments and adjunctive options such as immunomodulators, bacteriophages, and AI-driven decision support. Continued research in ICU-specific populations, especially regarding pharmacokinetics in patients on ECMO or CRRT, is urgently needed. In summary, while the therapeutic landscape for carbapenem-resistant Gram-negative infections has evolved substantially, sustained success will rely on a multifaceted strategy combining innovation, precision, and prevention to improve outcomes for the most vulnerable patients.
    Keywords:  BL-BLI; CRAB; Gram-negative bacteria; antimicrobial stewardship; carbapenem-resistant infections; intensive care unit
    DOI:  https://doi.org/10.3390/diagnostics16071053
  17. Respir Med. 2026 Apr 15. pii: S0954-6111(26)00191-5. [Epub ahead of print] 108823
       BACKGROUND: Pulmonary infections remain the main cause of morbidity and mortality in cystic fibrosis (CF), despite advances in supportive care and targeted therapies. Since the mid-20th century, research on CF-associated pulmonary infections has expanded substantially, reflecting increasing clinical complexity, evolving pathogens, and antimicrobial resistance. This study aimed to evaluate global research trends related to pulmonary infections in CF between 1950 and 2025 using a bibliometric approach.
    METHODS: A bibliometric analysis was performed using the Scopus database. A disease-centered search strategy was applied without restrictions on pathogens or interventions. Peer-reviewed articles and reviews published up to December 13, 2025 were included, while publications indexed in 2026 and records with missing country affiliation data were excluded.Bibliometric indicators including publication output, journals, countries, institutions, authors, and author keywords were analyzed.Keyword co-occurrence analysis was conducted using VOSviewer to identify major research themes.
    RESULTS: A total of 8,484 publications were included.Research output increased steadily, with a notable rise after the early 2000s and a peak in 2021. Most publications were written in English and classified mainly under Medicine, Immunology and Microbiology, and Biochemistry, Genetics and Molecular Biology. The United States,the United Kingdom,and Germany were the most productive countries. Keyword analysis revealed major thematic clusters related to chronic pulmonary disease, antimicrobial therapy and resistance, and pathogen-focused research, with Pseudomonas aeruginosa emerging as the most prominent pathogen.
    CONCLUSION: This bibliometric analysis summarizes the evolution of global research on CF-associated pulmonary infections, highlighting sustained emphasis on chronic infection and antimicrobial resistance, and may help guide future research priorities.
    Keywords:  Antimicrobial resistance; Bibliometric analysis; Cystic fibrosis; Pseudomonas aeruginosa; Pulmonary infection
    DOI:  https://doi.org/10.1016/j.rmed.2026.108823
  18. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2026 Apr 13.
      The increasing use of antibiotics both in human therapy and for non-therapeutic applications with simultaneous reduction in antibiotic drug development have led to a world-wide rise in antibiotic resistance. Before the age of antibiotics, bacteriophages (phages) were already used initially in France and Georgia and later in the USA and Russia. Today, phages are increasingly being used to treat infections caused by antibiotic-resistant bacteria either alone or in combination with antibiotics.Combining phages with antibiotics reduces the likelihood of simultaneous resistance development against both agents. In contrast to chemically defined antibiotics, phages have the ability to adapt to resistant host cells through genetic mechanisms. However, bacterial mutants that confer antibiotic resistance could simultaneously limit the effectiveness of phages. To avoid such effects, detailed knowledge of the mechanism of action and resistance of the antibiotic as well as the replication strategy of the phage is required. For the individual steps in the replication cycle of the lytic phages, the possible effects on resistance to the corresponding phages are analyzed for host cell factors associated with antibiotic resistance. Based on selected combinations, it becomes evident that resistance to one component is often accompanied by increased sensitivity to the other, which significantly reduces the likelihood of simultaneous resistance to both. Particularly efficient appear to be synergistic combinations, such as those consisting of an antibiotic and endolysin, a bactericidal phage enzyme.
    Keywords:  Adaption; Antibiotic resistance; Bacteriophage; Combination therapy; Endolysin
    DOI:  https://doi.org/10.1007/s00103-026-04232-8
  19. Adv Wound Care (New Rochelle). 2026 Apr 12. 21621918261441046
       SIGNIFICANCE: Chronic wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers are characterized by impaired healing and persistent inflammation. Cellular senescence, defined as irreversible growth arrest with a pro-inflammatory secretory phenotype (senescence-associated secretory phenotype), has emerged as a potential driver of these nonhealing states. While transient induction of senescence may aid acute repair, chronic accumulation of senescent cells is thought to disrupt tissue regeneration, promote extracellular matrix degradation, and sustain inflammation.
    RECENT ADVANCES: Single-cell RNA sequencing and spatial transcriptomics have revealed diverse cell states in chronic wounds, including senescent subsets. Studies in diabetic, venous, and pressure ulcers implicate senescent fibroblasts and immune cells in impaired remodeling, often triggered by oxidative stress, hyperglycemia, or ischemia-reperfusion injury. Therapeutic strategies targeting senescent cells in delayed wound healing have demonstrated promise in preclinical models; however, interventions must be timed and targeted precisely.
    CRITICAL ISSUES: Despite emerging evidence, the identity, abundance, and location of senescent cells in chronic wounds remain poorly defined. Reliance on nonspecific markers such as p21 or SA-β-gal complicates interpretation. Senescence appears to play context-dependent roles, with beneficial effects during acute healing but harmful persistence in chronic wounds, presenting challenges for therapeutic targeting.
    FUTURE DIRECTIONS: More studies using single-cell RNA sequencing, spatial transcriptomics, and longitudinal profiling are needed to define senescent subpopulations, map their spatial distribution, and track dynamics during wound progression. These approaches will help distinguish transient from persistent senescence. A deeper understanding of interactions with immune, epithelial, and stromal components will guide precisely timed, cell type-specific interventions to improve outcomes.
    Keywords:  cellular senescence; chronic wounds; fibroblast senescence; senescence-associated secretory phenotype; wound healing
    DOI:  https://doi.org/10.1177/21621918261441046
  20. Int J Biochem Cell Biol. 2026 Apr 14. pii: S1357-2725(26)00051-8. [Epub ahead of print] 106947
      Diabetic foot ulcers (DFU) represent a severe chronic complication of diabetes with increasing global prevalence. Approximately 75% of lower limb amputations are attributable to diabetic foot disease, and the 5-year mortality rate following amputation ranges from 53% to 100%. The pathogenesis of DFU involves multiple interacting factors, among which programmed cell death (PCD) plays a central role in impaired wound healing. Dysregulation of PCD modalities, including apoptosis, ferroptosis, pyroptosis, and autophagy, interacts with oxidative stress and immune dysfunction to create a pathological microenvironment that perpetuates tissue damage and delays repair. This narrative review is based on literature searches in PubMed, CNKI, and Web of Science up to 2026 using keywords related to DFU and PCD. It provides a comprehensive overview of the molecular mechanisms underlying different PCD pathways in DFU, explores their complex interrelationships and synergistic effects on wound healing, and discusses emerging therapeutic strategies targeting these cell death modalities. A deeper understanding of PCD regulatory networks may facilitate the development of novel therapeutic approaches and improve clinical outcomes for patients with DFU.
    Keywords:  Apoptosis; Autophagy; Diabetic Foot Ulcer; Ferroptosis; Pyroptosis
    DOI:  https://doi.org/10.1016/j.biocel.2026.106947
  21. Cureus. 2026 Mar;18(3): e105081
      Chronic wounds, particularly diabetic foot ulcers (DFUs) and burn wounds (BWs), impact millions of individuals globally and generate substantial healthcare costs, highlighting the urgent need for more effective therapies aimed at controlling infections. Currently, there is growing evidence of beneficial effects of selected bacterial strains, including Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Bifidobacterium longum, and Escherichia coli, as well as fungi from the genus Saccharomyces spp. Each of these species exerts a distinct influence on the wound microenvironment. This review compiles evidence from PubMed-indexed studies published between 2016 and 2026 regarding the application of external dressings and other topically administered formulations containing probiotic or postbiotic preparations in the management of DFUs and BWs. Probiotic strains facilitate wound healing through various mechanisms, including the secretion of antimicrobial metabolites (such as organic acids, hydrogen peroxide, and bacteriocins), inhibition of biofilm formation by pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, immunomodulation, local acidification, and stimulation of growth factors and components of the extracellular matrix. Various methods for delivering microorganisms with probiotic properties are being evaluated. These approaches can be broadly divided into two main categories: probiotic-containing dressings and non-dressing-based methods (i.e., ointments or biohybrid microneedles). It is indicated that postbiotics - metabolic byproducts or structural components of microbial cells - may likewise contribute positively to wound repair. A reduction in pathogen load and positive healing outcomes in DFUs and venous or burn ulcers with L. plantarum dressings is indicated, although evidence sizes are still limited. Current evidence suggests that probiotic-based dressings could serve as a promising adjunctive strategy in the management of chronic wounds; however, further well-designed clinical trials are necessary to validate efficacy, identify optimal strains and carriers, and assess long-term safety. While a large body of in vitro and animal model data exists, robust evidence from randomized controlled trials in humans remains scarce.
    Keywords:  burn wound; chronic wound; diabetic ulcer; dressings; lactobacillus plantarum; probiotics; wound healing
    DOI:  https://doi.org/10.7759/cureus.105081
  22. Adv Healthc Mater. 2026 Apr 14. e05375
      Wound healing is a complex and dynamic biological process that can be disrupted by various pathological factors, including abnormal inflammatory responses, biofilm formation, impaired angiogenesis, neural dysfunction, and pathological fibrosis. Such complexities pose substantial challenges in wound management, highlighting the urgent need for advanced, adaptive, and comprehensive therapeutic strategies. Recently, microneedles (MNs) have garnered significant attention in wound healing for their remarkable ability to penetrate tissue barriers and deliver therapeutics efficiently. However, there remains a lack of comprehensive reviews that systematically bridge the gap between advanced material design and the hurdles of clinical translation. This review summarizes recent advancements in MN technology, analyzing the design evolution from passive delivery tools to bioactive, stimuli-responsive scaffolds and smart systems with integrated sensing and feedback capabilities. Additionally, we explore stage-specific therapeutic strategies across different wound types to address specific barriers such as exudate management and labile payload stability. Finally, we critically assess translational requirements - including sterility assurance, mechanical safety, and regulatory considerations for drug-device combination products - to support the development of clinically deployable MN technologies.
    Keywords:  clinical translation; intelligent wound care; microneedles; transdermal drug delivery; wound healing
    DOI:  https://doi.org/10.1002/adhm.202505375
  23. ISME J. 2026 Apr 11. pii: wrag077. [Epub ahead of print]
      Phages infect bacteria by binding to specific surface receptors, driving co-evolution in microbial communities and offering therapeutic potential. However, how receptor specificity shapes the cross-resistance patterns and evolutionary trade-offs during phage-bacteria co-evolution remains unclear. Here, we investigated the genetic basis and fitness trade-offs of phage resistance in Salmonella to phages targeting O-antigen, core oligosaccharide, and BtuB (TonB-dependent receptor for vitamin B12) under individual or combinatorial pressures. The interaction matrices between phage-resistant strains and phages targeting three different receptors showed that bacterial cross-resistance to phages depends on the receptor type. Lipopolysaccharide (LPS) truncation conferred cross-resistance to phages targeting either the O-antigen or core oligosaccharide; whereas resistance to phages targeting BtuB occurred exclusively through mutations in the btuB gene. For LPS receptors whose biosynthesis involves multiple genes, the fitness cost associated with phage resistance is gene-specific. Among mutations conferring resistance to both O-antigen-targeting and core-targeting phages, those in the rfaJ gene exhibited the lowest fitness cost. The three-phage combination targeting three receptors exhibited potent antibacterial effects. Under this selective pressure, Salmonella developed resistance through receptor modification. Resistance to O-antigen-targeting and core-targeting phages emerged first through mutations in LPS biosynthesis genes, with mutations in the rfaJ gene dominating. Subsequently, mutations in the btuB gene accumulated to resist BtuB-targeting phages, ultimately evading predation by all three phages. Our results reveal receptor-driven evolutionary trade-offs and sequential resistance acquisition in Salmonella under multiple phages pressure, enhancing understanding of microbial interactions and informing phage therapy strategies.
    Keywords:  co-evolution; evolutionary trade-offs; phage receptors; phage resistance
    DOI:  https://doi.org/10.1093/ismejo/wrag077
  24. Appl Microbiol Biotechnol. 2026 Apr 16.
      Staphylococcus aureus strains cause a wide range of infections in humans, often with the potential for complications such as surgical site infections. The production of Panton-Valentin leukocidin (PVL) by certain strains of S. aureus is clinically associated with chronic or recurrent infections, which typically require decolonization, most often with mupirocin. As increased mupirocin use promotes the emergence of resistance, this study investigated the coadministration of mupirocin and therapeutic Kayvirus bacteriophage as a potential strategy to enhance treatment efficacy and prevent the development of new resistance. We collected and evaluated 37 PVL-encoding S. aureus strains from wound samples. Among these, 22% were methicillin-resistant, and 11% were resistant to the tested phage, but all were susceptible to mupirocin. To assess interactions between mupirocin and the phage in PVL-positive strains with varying levels of mupirocin resistance, we used lysogenization by PVL-encoding phage and adaptive laboratory evolution of clinical strains. In mupirocin-susceptible strains, lytic phage efficacy decreased due to altered protein synthesis caused by the interaction of mupirocin with isoleucyl-tRNA synthetase, whereas mupirocin efficacy was unaffected. In contrast, the advantage of combined administration was observed in mupirocin-resistant strains susceptible to phages, as their altered or alternative synthetase allowed protein synthesis to continue, enabling phage proliferation and bacterial lysis, even in the presence of mupirocin. This in vitro study demonstrates that mupirocin in combination with Kayvirus broadens the spectrum of strains susceptible to treatment and that the phage used prevents the development of mupirocin resistance. KEY POINTS: • Mupirocin-phage combination broadens the anti-staphylococcal effect in vitro. • Combination treatment reduces the emergence of mupirocin resistance. • Mupirocin action is not inhibited by phage therapy.
    Keywords:   Kayvirus ; Staphylococcus aureus ; Decolonization; Mupirocin; Panton-Valentine leukocidin; Phage therapy
    DOI:  https://doi.org/10.1007/s00253-026-13814-0
  25. J Periodontol. 2026 Apr 13.
       BACKGROUND: Periodontitis is an inflammatory disease of the oral cavity driven by bacterial dysbiosis that progressively breaks down the tooth-supporting structures.
    METHODS: This study leverages a uniquely large dataset of up to 34,000 patient records in the United States analyzed using standardized real-time polymerase chain reaction-based molecular testing to quantify bacterial profiles associated with periodontitis. Our analysis focused on 11 bacterial taxa from the red, orange, and green complexes. We assessed bacterial abundance, expressed as genome copies per milliliter, across periodontitis stages and associations with age and systemic conditions.
    RESULTS: Across stages 1-4 (according to the American Academy of Periodontology classification), the concentration of the three red complex bacteria, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola increased up to 11-fold, the highest increase observed among all studied bacteria. A substantial microbial shift in younger patients was observed, while older individuals exhibited a higher prevalence of red complex pathogens. The relative abundance of P. gingivalis increased significantly, from 4% in stage 1 periodontitis to 17% in stage 4. Cumulative bacterial load analysis based on the presence or absence of red complex bacteria revealed that the median bacterial load was 5-fold higher in samples where red complex bacteria were present. The inter-bacterial correlations increased with demographic and clinical variables as periodontitis advanced.
    CONCLUSION: The findings revealed a significant positive association between increased bacterial loads, particularly red complex bacteria and higher periodontitis stages, positioning them as a key indicator of dysbiosis and a potential biomarker for disease advancement.
    PLAIN LANGUAGE SUMMARY: Periodontitis is a serious gum disease that damages the tissues supporting the teeth. It is caused by harmful bacteria in the mouth and becomes worse over time if not treated. In this study, we analyzed oral rinse samples collected from more than 34,000 people using a DNA-based method to measure the levels of different bacteria. We focused on 11 bacteria known to be involved in gum disease and compared their presence in healthy versus mild to severe cases. We found that three bacteria, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, became much more common as the disease got worse, with one of them, P. gingivalis, increasing 4-fold in severe cases compared with mild ones. Older adults were more likely to have these harmful bacteria, but younger patients showed notable shifts in their bacterial makeup as well. These results suggest that certain bacteria, especially P. gingivalis, may serve as warning signs for more advanced gum disease. Our findings could help to improve how gum disease is diagnosed and tracked, leading to better care and prevention. This is the largest study of its kind and offers new insight into the role of bacteria in oral health.
    Keywords:  bacteria; dysbiosis; molecular diagnostics; oral rinse; periodontitis; red complex
    DOI:  https://doi.org/10.1002/jper.70122
  26. Tissue Cell. 2026 Apr 14. pii: S0040-8166(26)00227-2. [Epub ahead of print]102 103534
      A wound is defined as a disruption of the epithelial lining of the skin or mucosa caused by thermal or physical injury, and it is categorized into two types: acute and chronic. Wound healing involves the regeneration of damaged epithelial tissues and occurs in four phases: hemostasis, inflammation, proliferation, and remodeling. Emerging evidence indicates that microorganisms in the gut and on the skin contribute to healing in intestinal mucosal and cutaneous wounds, respectively. Recently, there has been a surge in studies on the gut-skin axis, which has significantly improved our understanding of how the gut and skin microbiota influence wound healing. This review focuses on preclinical findings regarding gut and skin microbes and their roles in healing processes. It explores probiotics as therapeutic options to maintain the integrity of gut and skin epithelial barriers against damage or injury. The literature on gut and skin microbiota in wound healing was extensively reviewed. The search, conducted across various databases [PubMed®, Google Scholar®, Scopus®, ResearchGate®, Web of Science®, Multidisciplinary Digital Publishing Institute (MDPI)®, Science Direct®, Scopus (Elsevier)] using key terms, included English-language publications up to July 2025. Understanding the specific mechanistic links between gut and skin microbiota and the epithelial regeneration process can deepen our knowledge of the receptor and signaling pathways involved in wound healing. This understanding highlights the importance of preventing dysbiosis in the gut and skin microbiota to support epithelial and mucosal health.
    Keywords:  Dysbiosis; Gut-skin axis; Microbiota; Probiotics; Wound healing; Wounds
    DOI:  https://doi.org/10.1016/j.tice.2026.103534
  27. J Med Microbiol. 2026 Apr;75(4):
      Diabetic foot disease is a major public health problem, with an annual National Health Service (NHS) expenditure exceeding £1 billion. Infection increases the risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to correctly and rapidly isolate pathological organisms with conventional culture techniques and deliver appropriate narrow-spectrum antimicrobials. Rapid DNA-based technology, using multi-channel arrays, offers a quicker alternative and has previously been used effectively in other settings. We undertook a prospective cohort study of deep tissue samples taken from diabetic foot ulcers (DFUs), comparing samples processed by conventional culture and real-time PCR TaqMan array card (TAC). Fifty samples were taken from 39 patients. The ulcers were of variable chronicity prior to sampling (range: 1-113 weeks) and were sited on the heel (3), midfoot (6) and forefoot (41). TAC results were available an average of 4.3 days earlier than culture results. Seventeen samples had the same organisms detected on culture and TAC. Sixteen of these 17 had additional organisms detected by TAC. The most frequent organisms detected by TAC that were not detected by culture were staphylococci, Enterobacter spp., Pseudomonas spp. and fungi. TAC rapidly and accurately detects clinically relevant organisms from DFUs, providing earlier results than standard culture. This may enable earlier rationalization of antimicrobials and infection control interventions.
    Keywords:  TaqMan array; diabetic foot infection (DFI)
    DOI:  https://doi.org/10.1099/jmm.0.002113
  28. Front Cell Infect Microbiol. 2026 ;16 1761564
       Introduction: The global rise of antimicrobial resistance has positioned multidrug-resistant Klebsiella pneumoniae as a critical health threat, necessitating alternative therapeutic strategies such as phage therapy. However, the long-term evolutionary consequences of phage-bacteria interactions remain poorly understood. This study characterizes a unique attenuated mutant, wGF 1-2, derived from a hypervirulent K. pneumoniae strain (GF) during phage isolation efforts.
    Methods: The wGF 1-2 mutant was serendipitously isolated during attempts to obtain lytic phages against the parental GF strain. We performed an integrated multi-omics and phenotypic characterization, including genomic sequencing, proteomic profiling, and transcriptomic analysis. Host-pathogen interactions were assessed using a murine infection model (evaluating survival and tissue colonization), and the impact on the gut microbiota was analyzed via metagenomics.
    Results: Compared to the parental strain, wGF 1-2 exhibited a significant reduction in biofilm formation and distinct morphological alterations. In a murine model, the mutant was avirulent, resulting in 100% survival even at a high challenge dose (10⁶ CFU), with minimal tissue colonization. Multi-omics analysis revealed extensive genomic structural variations (81 insertions and 64 deletions). Proteomic shifts included the downregulation of proteins involved in metal ion binding and metabolic pathways. Furthermore, infection with wGF 1-2 led to host inflammatory suppression and a restructuring of the gut microbiota characterized by an increase in beneficial Bacteroidota.
    Discussion: This study provides a comprehensive characterization of an attenuated K. pneumoniae mutant, wGF 1-2. The extensive genomic and phenotypic alterations observed highlight the significant evolutionary potential of bacterial pathogens during phage interactions. These findings underscore the necessity of thorough safety assessments, including evolutionary risk evaluations, for the future development of phage-based therapies.
    Keywords:  Klebsiella pneumoniae; biofilm formation; multi-omics; phage; virulence
    DOI:  https://doi.org/10.3389/fcimb.2026.1761564
  29. Front Immunol. 2026 ;17 1793958
      Chronically infected wounds continue to pose a major challenge in clinical practice. Their persistence reflects the convergence of sustained microbial colonization, inappropriate or prolonged immune activation, and insufficient tissue regenerative capacity, which together establish a self-reinforcing pathological environment. In routine clinical management, approaches centered on debridement and antimicrobial therapy often fail to achieve durable healing, indicating that key regulatory mechanisms governing wound repair remain insufficiently understood. Accumulating evidence has drawn attention to adipocytes as an integral, yet previously underrecognized, component of the infected wound microenvironment. Beyond their established metabolic role, adipocytes respond rapidly to infectious injury and contribute to early host defense through several coordinated processes. These include migration-associated morphological remodeling that provides transient coverage at the wound margin, local production of antimicrobial peptides that directly restrict microbial growth, and secretion of complement components and chemotactic mediators that shape the recruitment and function of innate immune cells such as neutrophils and macrophages. As infection is brought under control, adipocyte activity shifts toward supporting tissue repair, with paracrine signals influencing fibroblast behavior, angiogenesis, re-epithelialization, and granulation tissue development. On this basis, this review summarizes current knowledge of adipocyte functions across distinct phases of infected wound healing and discusses emerging translational strategies that leverage adipocyte biology, including refinements in autologous fat grafting and the development of adipose-derived biomaterials. A clearer understanding of adipocyte functional plasticity may help guide therapeutic approaches that integrate immune regulation with regenerative processes, thereby improving outcomes in chronic, non-healing wounds.
    Keywords:  AMPs; adipocytes; fat grafting; immune regulation; infected wounds; tissue regeneration; wound healing
    DOI:  https://doi.org/10.3389/fimmu.2026.1793958
  30. bioRxiv. 2026 Apr 10. pii: 2026.04.09.717493. [Epub ahead of print]
      Chronic antibiotic-resistant cystic fibrosis (CF) lung infections are the leading cause of death in adults with CF. Despite advances in highly effective modulator therapies, microbial communities persist in the CF lung. The pathogenesis of CF airway infections can be exacerbated by pathogens such as Pseudomonas aeruginosa, which communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. However, most CF lung infections are polymicrobial in nature, and therefore, the contribution of polymicrobial bEVs remains to be determined. By using a polymicrobial culture model representing a 'pulmotype' detected in ∼34% of lung infections in people with CF (pwCF), comprised of P. aeruginosa , Staphylococcus aureus , Streptococcus sanguinis , and Prevotella melaninogenica grown in synthetic sputum medium under anoxia, we report that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by enhancing virulence, biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. Elexacaftor/Tezacaftor/Ivacaftor (ETI), a highly effective modulator therapy, does not ameliorate the response or return it to WT levels. Bacterial EVs also inhibited ETI CFTR Cl - currents by CF pHBEC. These studies provide insight into why ETI does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.
    IMPORTANCE: Cystic fibrosis (CF) is a genetic disease characterized by chronic polymicrobial lung infections that, if untreated, are one of the primary causes of death in CF. Elexacaftor/Tezacaftor/Ivacaftor (ETI) has many positive clinical outcomes, but it does not eliminate chronic polymicrobial lung infections or inflammation. Using a new biologically relevant co-culture model, we have demonstrated that bacteria secrete vesicles (bEVs) that contain proteins and RNAs. We observed that these RNA-loaded bEVs are predicted to promote the pathogenesis of chronic CF lung infections by enhancing bacterial virulence and biofilm formation, as well as upregulating the pro-inflammatory response in lung cells. ETI does not ameliorate the response of lung cells to bEVs. Our research will facilitate the development of more effective approaches to eliminate infection and inflammation in CF and other lung diseases characterized by chronic polymicrobial infections and excessive inflammation.
    DOI:  https://doi.org/10.64898/2026.04.09.717493
  31. bioRxiv. 2026 Apr 09. pii: 2026.04.08.717253. [Epub ahead of print]
      Serratia marcescens is an opportunistic pathogen that causes severe hospital-acquired infections, notable for its biofilm formation abilities and development of extensive antibiotic resistance. Here we evaluated the efficacy of bacteriophages, antibiotics, and antimicrobial peptides (BAP), alone and in combination, against fourteen multi-drug-resistant (MDR) S. marcescens isolates sourced from hospitals and other environmental settings in an in vitro biofilm model. Phage combination with a cocktail of sub-minimal inhibitory concentration (MIC) of penicillin-streptomycin, kanamycin, and ciprofloxacin, reduced biofilm biomass, however, complete decolonization was not achieved. Incorporating an antimicrobial peptide cocktail into this regimen eradicated 99.99% of multi-drug-resistant isolates grown planktonically or in surface-associated biofilms. Microscopy and viability assays confirmed extensive biofilm disruption and bacterial clearance without regrowth. These findings reveal that simultaneous interference of cell wall synthesis, protein translation, DNA replication, and membrane integrity can overcome S. marcescens antimicrobial defenses, establishing a multifaceted therapeutic framework for managing device-associated infections caused by MDR pathogens.
    DOI:  https://doi.org/10.64898/2026.04.08.717253
  32. ACS Appl Bio Mater. 2026 Apr 14.
      Chronic wounds are complex and dynamic environments that pose challenges due to impaired healing and bacterial infections, which are increasingly difficult to address because of antimicrobial resistance. Therefore, the infected and damaged tissue at the wound site requires advanced measures to ensure efficient regeneration, highlighting the need for a combinatorial approach. In this direction, this study aims to develop a composite biomaterial using 2-hydroxyethylmethacrylate (HEMA)-chitosan (HC) cryogels as a biomaterial matrix. Further, these HC cryogels will be incorporated with the bacteriophages (phages) against Klebsiella pneumoniae, along with phytoextracts of Berberis aristata (Darvi) in powder (P) formulation, and Trichosanthes dioica (Patola), Azadirachta indica (Neem), and Pongamia pinnata (Karanja) together in oil (O) formulation. The physicochemical properties of the developed composite cryogels were evaluated through swelling studies, mechanical testing, and degradation analysis. The antimicrobial properties against K. pneumoniae were observed in phage-containing cryogels through an agar diffusion assay, colony forming unit assay, and phage release was also determined over a 24-hour period. Further, biological studies showed negligible cytotoxicity, as confirmed by a direct contact test with L929 fibroblast cells. The MTT assay and live-dead staining on days 1, 3, and 7 showed significantly enhanced cell proliferation in the HC-O and HC-PO groups in comparison to the HC and HC-P groups. The wound-healing potential of the composite cryogels, assessed using a scratch assay, further demonstrated the highest healing in the HC-PO group. Therefore, this study provides evidence for the wound-healing potential of the as-developed composite cryogels due to their bifunctional role in phage-mediated antimicrobial properties and enhanced fibroblast migration as well as proliferation under the influence of phytoextracts.
    Keywords:  antimicrobial resistance; bacteriophage; chronic wound; cryogel; phytoextract
    DOI:  https://doi.org/10.1021/acsabm.5c02578
  33. Ann N Y Acad Sci. 2026 Apr;1558(1): e70258
      The nasal microbiome, an integral component of the upper respiratory tract's microecological system, plays a pivotal role in inflammatory diseases such as allergic rhinitis and chronic sinusitis, which affect a substantial population and markedly reduce quality of life. A healthy nasal flora and its metabolites are crucial for maintaining immune homeostasis and mucosal barrier integrity. This review comprehensively discusses the pathological mechanisms, immune interactions, and clinical intervention strategies involving the nasal microbiota in nasal inflammation. It has been shown that dysbiosis of the nasal flora disrupts immune function and compromises the epithelial barrier, thereby initiating and exacerbating a vicious cycle of inflammation. Furthermore, the formation of bacterial biofilms and the emergence of drug resistance contribute to persistent and recurrent symptoms. Regarding treatment, while antibiotics may offer short-term efficacy, they risk aggravating the microbial imbalance. In contrast, therapies including probiotics, novel immunomodulators, and traditional Chinese medicine demonstrate significant therapeutic potential by restoring microbial balance and modulating immune responses. This review synthesizes current research to provide new perspectives for understanding host-microbiome interactions and to guide future clinical treatments and drug development.
    Keywords:  bacterial metabolites; immune response; inflammatory nasal diseases; nasal microbiota; therapeutic strategies
    DOI:  https://doi.org/10.1111/nyas.70258
  34. J Periodontol. 2026 Apr 13.
       BACKGROUND: The microbiome is a dynamic system that changes throughout life. Studies have revealed the relationship between periodontal disease and the oral microbiota; however, the impact of periodontal disease on the expression of senescence markers and on the inflammaging of the oral and systemic microbiome remains unclear. We hypothesized that aging increases the periodontitis-induced changes in the oral and systemic microbiome and is accompanied by an altered inflammatory response.
    METHODS: Experimental periodontitis was induced in 18-month-old (old) and 8-month-old (young) C57BL/6 mice by placing ligatures around the second maxillary molars. Bone morphometric analyses were conducted to assess bone loss. Senescence- and inflammatory-related gene expression in the gingiva was measured by quantitative polymerase chain reaction (qPCR). Serum inflammatory markers were evaluated via immunoassay. Oral, brain, and gut microbial content were analyzed using next-generation sequencing.
    RESULTS: Maxillary bone loss was significantly higher in the old mice with periodontal disease than in young mice. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. The alpha diversity of the oral and brain microbial communities differed significantly between old and young mice. Treponema denticola, Fusobacterium nucleatum, Porphyromonas gingivalis, P. pasteri, and Prevotella nigrescens were only detected in the brains of old animals with periodontitis.
    CONCLUSION: Periodontopathogens and oral commensals are either only found in the brains of old animals with periodontal disease or are more prevalent in the brains of old animals, suggesting that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain.
    PLAIN LANGUAGE SUMMARY: Aging may increase the periodontitis-induced changes in the oral and systemic microbiome, which an altered inflammatory response may accompany. Experimental periodontitis was created in old and young mouse models. Bone loss, senescence, and inflammatory gene expression and serum inflammatory markers were assessed in each model, and oral, brain, and gut microbial content was analyzed. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. Our results suggested that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain.
    Keywords:  brain microbiome; inflammaging; oral microbiome; periodontitis; senescence
    DOI:  https://doi.org/10.1002/jper.70118
  35. Adv Wound Care (New Rochelle). 2026 Apr 15. 21621918261440435
       BACKGROUND: Diabetic foot ulcers (DFUs) remain one of the most devastating complications of diabetes, accounting for over 80% of nontraumatic amputations and contributing to a 5-year mortality rate exceeding 30%. Despite significant clinical advances, profound disparities persist. Racial and ethnic minoritized populations, rural communities, and people with low socioeconomic resources experience disproportionate rates of severe ulceration, infection, delayed healing, and amputation.
    PROBLEM: Traditional research approaches, often developed in academic settings without community input, have insufficiently addressed the contextual, cultural, and structural factors shaping DFU risk and outcomes.
    APPROACH: Community-engaged research (CEnR) offers a promising pathway to address these inequities; yet, DFU-specific evidence remains limited and heterogeneous. In response, the Diabetic Foot Consortium (DFC), a national research network funded by the National Institute of Diabetes and Digestive and Kidney Diseases, has initiated multisite efforts to embed community advisory boards, faith-based partnerships, mobile outreach, and culturally aligned engagement into DFU research.
    MODEL: We propose the DFC-CEnR Model, a conceptual framework for integrating community-engaged approaches to DFU prevention, early detection, treatment, and research participation. The model distinguishes CEnR from related approaches (community-based participatory research, patient and public involvement, cultural humility, and equity-focused system interventions), outlining hypothesized mechanisms and evaluation domains. Illustrative consortium examples demonstrate how engagement domains may be operationalized and inform future testing of validated outcome measures.
    IMPLICATIONS: This article positions community engagement as a hypothesis-generating strategy that requires rigorous empirical testing to determine its impact on DFU outcomes and disparities.
    Keywords:  community engaged research; culturally competent care; diabetic foot ulcers; stakeholder engagement; underserved populations; wound care
    DOI:  https://doi.org/10.1177/21621918261440435
  36. J Oral Biol Craniofac Res. 2026 May-Jun;16(3):16(3): 101446
       Background: Periodontitis is a chronic inflammatory disease associated with oral microbiome dysbiosis, where Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis contribute through adhesion, biofilm formation, and tissue-destructive virulence factors. Although chlorhexidine is widely used as an adjunctive antimicrobial agent, its long-term use is limited by adverse effects, highlighting the need for safer natural alternatives. Red ginger (Zingiber officinale var. rubrum) exhibits antibacterial potential; however, data on fractionated extracts and their interaction with specific virulence proteins remain limited.
    Objective: To evaluate the antibacterial activity of fractionated ethanolic red ginger extract against A. actinomycetemcomitans and P. gingivalis using integrated in silico and in vitro approaches.
    Methods: Twenty-two bioactive compounds identified from the fractionated extract were analyzed via molecular docking against cytolethal distending toxin (Cdt) of A. actinomycetemcomitans and fimbrial protein Mfa5 of P. gingivalis, with chlorhexidine as reference. In vitro assays determined minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), bacterial adherence, biofilm formation, and viability.
    Results: Docking analysis showed that cyclooctacosane and gamma-sitosterol demonstrated binding affinities comparable to chlorhexidine toward both target proteins. The extract exhibited MIC/MBC values of 0.062/0.125 mg/mL for A. actinomycetemcomitans and 0.031/0.062 mg/mL for P. gingivalis. Significant reductions in bacterial adherence, biofilm formation, and viability were observed at concentrations of 0.031-0.125 mg/mL.
    Conclusion: Fractionated ethanolic red ginger extract demonstrates promising antibacterial activity against key periodontal pathogens by targeting virulence mechanisms related to adhesion and biofilm formation, supporting its potential as a natural adjunct in periodontal therapy.
    Keywords:  Aggregatibacter actinomycetemcomitans; Antibacterial activity; Medicine; Periodontitis; Porphyromonas gingivalis; Zingiber officinale
    DOI:  https://doi.org/10.1016/j.jobcr.2026.101446
  37. Clin Transl Sci. 2026 Apr;19(4): e70561
      This Perspective examines Thailand's role in cell and gene therapy, focusing on regulatory development and early clinical experience. These therapies are used in Thailand for β-thalassemia, or blood cancer, together with the evolving ATMP regulatory framework and the ATMP Sandbox Project. Rather than cataloguing global indications, we analyze how selected advances intersect with Thailand's health system, highlighting opportunities and constraints for its role as a regional site for ATMP research, manufacturing, and access in Southeast Asia.
    Keywords:  advanced therapeutic medicinal products (ATMPs); gene addition; gene editing; gene therapy; sandbox project
    DOI:  https://doi.org/10.1111/cts.70561
  38. Cell Host Microbe. 2026 Apr 15. pii: S1931-3128(26)00125-3. [Epub ahead of print]
      Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection and is increasingly being explored for other microbiota-associated diseases. However, general research has largely focused on bacterial engraftment, overlooking the contribution of the gut virome. In this perspective, we highlight phage-mediated horizontal gene transfer (HGT) as a potentially influential process occurring following FMT. Donor-derived phages may potentially influence community structure, engraft in resident bacteria, and modulate microbial functions or host physiology. In addition, temperate phages are well-equipped to mobilize bacterial genes, such as metabolic functions, stress-response traits, and antibiotic resistance determinants, raising the possibility that gene flow could well contribute to FMT outcomes. We propose a conceptual model in which phages act as bidirectional mediators of adaptation, not only accompanying bacterial communities but also influencing gut ecosystems in subtle, yet potentially consequential, ways.
    Keywords:  Bacteriophage; FMT; HGT; microbiome; virome
    DOI:  https://doi.org/10.1016/j.chom.2026.03.017
  39. J Imaging Inform Med. 2026 Apr 14.
      Diabetic foot ulcers, resulting from neuropathic and/or vascular complications in patients with diabetes mellitus, pose a major global health challenge. Early detection and consistent monitoring of wound progression are essential for timely intervention, effective treatment, and the prevention of severe complications such as amputation. In modern diabetic foot care, images captured using digital cameras and mobile phones are increasingly employed for remote wound assessment. In this context, automated segmentation of these wounds from such images plays a vital role by enabling objective and quantitative evaluation of wound areas-crucial for tracking the progression of healing over time. Recent years have witnessed growing interest in deep learning-based wound segmentation techniques, with a particular focus on models that are both computationally efficient and suitable for deployment on resource-constrained devices, including smartphones and point-of-care platforms. In this study, we propose a lightweight convolutional neural network (CNN) for diabetic foot wound segmentation that augments the U-Net architecture with ghost feature generation and Convolutional Block Attention Modules (CBAM) to improve computational efficiency and feature representation. The model was evaluated on a privately annotated dataset of 3450 diabetic foot wound images and compared against state-of-the-art architectures, including SegNet, U-Net, MobileNetV2, Mask R-CNN, and the domain-specific approach of Wang et al. We further investigated a fully automated two-step pipeline for wound segmentation incorporating a prior foot segmentation-based ROI detection. Using ROI detection, the proposed CNN achieved a precision of 85.13%, recall of 91.84%, Dice coefficient of 86.95%, and IoU of 77.23%. These results demonstrate competitive performance relative to high-capacity models while maintaining substantially reduced computational complexity, highlighting its suitability for real-time clinical deployment in low-resource environments.
    Keywords:  CNN; Convolutional neural network; Diabetic foot ulcer; Diabetic wounds; Segmentation
    DOI:  https://doi.org/10.1007/s10278-026-01941-z
  40. Front Drug Deliv. 2026 ;6 1793322
       Introduction: Messenger RNA (mRNA) therapeutics have advanced from experimental platforms to clinical application, driven largely by the success of lipid nanoparticle (LNP)-based COVID-19 vaccines. Building on this progress, nanoparticle-mediated mRNA delivery is being extended to non-infectious indications, including oncology, autoimmune disorders, and inherited diseases. However, challenges such as extrahepatic targeting, endosomal escape, repeat-dose immunogenicity, thermostability, and scalable manufacturing remain significant barriers to translation.
    Methods: A rapid review of peer-reviewed studies and registered clinical trials published between January 2020 and October 2025 was conducted. Searches were performed in PubMed, Scopus, Web of Science Core Collection, and ClinicalTrials.gov using combined terms related to RNA modality and nanoparticle delivery. Eligible studies focused on non-viral nanoparticle platforms for therapeutic, non-infectious mRNA delivery, including applications in protein replacement, genome editing, and immune modulation. Screening yielded 15 studies for inclusion.
    Results: LNPs remain the most clinically advanced platform for therapeutic mRNA delivery. At the same time, polymeric, peptide-based, exosome-inspired, and hybrid nanoparticle systems are expanding the delivery landscape. Emerging RNA formats, including self-amplifying RNA and circular RNA, show potential to prolong expression at lower doses. Clinically, individualized mRNA neoantigen therapy (mRNA-4157/V940) combined with pembrolizumab reduced recurrence risk by approximately 49% in high-risk melanoma in the KEYNOTE-942 phase 2b trial, supporting phase 3 development. In cystic fibrosis, inhaled CFTR mRNA (ARCT-032) advanced to phase 2 after early phase 1 data demonstrated safety and tolerability.
    Discussion: Evidence for non-viral nanoparticle-mediated mRNA therapeutics is strong in preclinical research and increasingly promising in clinical applications beyond vaccinology. While LNPs dominate current translation, alternative carriers and improved RNA formats may broaden tissue targeting and therapeutic durability. Advances in biodegradable ionisable lipids, organ-selective LNPs, and lyophilised or solid formulations are being developed to address persistent delivery and manufacturing constraints. As the field matures, regulatory and policy frameworks will need to align with therapeutic endpoints and support long-term safety monitoring.
    Keywords:  autoimmunity; cancer immunotherapy; circular RNA; genetic therapy; lipid nanoparticles; messenger RNA; non-viral delivery
    DOI:  https://doi.org/10.3389/fddev.2026.1793322
  41. Nat Commun. 2026 Apr 17.
      Identifying robust, non-invasive biomarkers of biological age is key to preventive medicine. While gut aging clocks exist, the oral microbiome remains underexplored as a quantitative biomarker. Using oral microbiome data from two NHANES cohorts (N = 4,675), we identified 64 age-dependent bacterial genera and developed a machine learning model predicting chronological age, with generalizability in an independent external cohort (N = 1,293). We derived an Oral Microbiome Aging Acceleration (OMAA) Score as the residual of predicted age against chronological age. The OMAA Score independently predicted all-cause mortality (HR = 1.05, P = 0.024) and frailty (OR = 1.05, P = 0.008), correlated with impaired kidney function (lower eGFR: β = -0.066, P = 5.22×10-4), and enhanced risk prediction for cancer (AUC 0.70 vs. 0.67, P = 0.009) and heart attack (AUC 0.79 vs. 0.76, P = 0.016) beyond conventional risk factors. Diet and medication had minimal association. The OMAA Score offers a scalable, non-invasive tool to identify high-risk individuals for age-related morbidity and mortality.
    DOI:  https://doi.org/10.1038/s41467-026-72096-2
  42. J Clin Med. 2026 Apr 07. pii: 2799. [Epub ahead of print]15(7):
      Background/Objectives: The rise in healthcare-associated infections caused by multidrug-resistant (MDR) bacteria in hospitals, particularly in intensive care units, has resulted in increased rates of morbidity and mortality, escalating costs, and has become a significant public health concern. In our Intensive Care Unit, we address healthcare-associated infections caused by multidrug-resistant bacteria, with a specific focus on those listed in the WHO 2024 List of Critically and Highly Prioritized Pathogens. Methods: Over the course of 1 year, from 1 January to 31 December 2024, we monitored the prevalence of healthcare-associated infections in the Intensive Care Unit of the Sibiu County Emergency Clinical Hospital, Romania, and the antibiotic susceptibility of the isolated bacteria. Results: The majority of infections were caused by pathogens in the ESKAPEE group. The most frequently isolated microorganism was Klebsiella pneumoniae (36.8%), followed by Acinetobacter baumannii (24.5%), classified as a critical priority by the WHO in 2024. Most positive samples for critical priority pathogens, including Klebsiella pneumoniae and Acinetobacter baumannii, as well as all MRSA strains (high priority), were obtained from tracheal aspirates collected from intubated and mechanically ventilated patients. A significant proportion of the isolated bacteria were multidrug-resistant, including extensively drug-resistant and pan-drug-resistant strains. Conclusions: The increase in antibiotic and antimicrobial resistance among hospital strains raises serious concerns about limited treatment options.
    Keywords:  ESKAPEE; MDR bacteria; MRSA; Romania prevalence; WHO 2024 BPPL; biofilms; carbapenem-resistant Klebsiella pneumoniae; intensive care infections
    DOI:  https://doi.org/10.3390/jcm15072799
  43. Int Dent J. 2026 Apr 13. pii: S0020-6539(26)00142-5. [Epub ahead of print]76(3): 109548
       BACKGROUND: Outer membrane vesicles (OMVs) from Gram-negative bacteria are spherical lipid bilayer nanostructures with diameters of 20 to 250 nm. Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, releases OMVs that mediate its virulence and systemic pathological effects.
    METHODS: This systematic review followed PRISMA guidelines and included studies from PubMed, Scopus, and Web of Science up to 2025.
    RESULTS: A total of 62 articles were incorporated into the analysis. Generally, OMVs of P. gingivalis play a role in mediating interbacterial communication and are involved in pathogen-host interactions. These processes contribute to periodontal tissue destruction and systemic dissemination via blood vessels, thereby being associated with multiple systemic diseases. Key findings are as follows: (1) Periodontal destruction: OMVs inhibit endothelial cells (ECs)-mediated osteogenesis via the cGAS-STING-TBK1 pathway and induce apoptosis in human periodontal ligament stem cells (hPDLSCs) through the msRNA45033-CBX5-p53 methylation axis. Moreover, OMVs induce ferroptosis in BMSCs via the Hippo-YAP pathway. (2) Oral squamous cell carcinoma (OSCC) progression: OMVs promote the development of OSCC by inducing NF-κB-regulated ferroptosis. Additionally, sRNA23392 within OMVs downregulates desmocollin-2, which impairs the invasion and migration of OSCC cells. (3) Systemic dissemination: OMVs can cross the blood-brain barrier (BBB) to transport bacterial components to distant organs, which is associated with Alzheimer's disease, cardiovascular disease, and diabetes mellitus. (4) Immune modulation: OMVs interact with macrophages and dendritic cells to trigger robust immune responses, inducing the secretion of pro-inflammatory cytokines.
    CONCLUSIONS: P. gingivalis OMVs act as key mediators of virulence dissemination and significantly modulate host-microbe interactions along the oral-systemic axis. This systematic review consolidates recent advancements in the research on P. gingivalis OMVs, emphasizing their roles in immunoregulation, pathogenic mechanisms, and associations with both periodontal and systemic diseases. Gaps in existing literature include strain-specific heterogeneity of OMVs and the dose-response relationships within systemic disease contexts. Future studies should employ multi-omics approaches and standardized methodologies to elucidate their heterogeneity and dose-response relationships, facilitating targeted therapies.
    Keywords:  Outer membrane vesicles; Periodontitis; Porphyromonas gingivalis; Systemic diseases; Therapeutic strategies; Virulence factors
    DOI:  https://doi.org/10.1016/j.identj.2026.109548
  44. ISME J. 2026 Apr 14. pii: wrag090. [Epub ahead of print]
      Reactive oxygen species are essential for cellular signalling and redox homeostasis, but their accumulation causes cellular oxidative stress. In inflammatory bowel disease, oxidative stress is linked to chronic inflammation and alterations in the gut microbiota. We hypothesised that these alterations may result from the impact of reactive oxygen species on the interactions between bacteria and their viruses, bacteriophages. We followed the evolution of three Escherichia coli strains and a virulent bacteriophage in a chemostat under continuous growth and studied the impact of oxidative stress on this community. We show that both the bacteriophage and its three hosts persisted in the system over 10 days, but the relative abundance of bacteriophages was decreased in the presence of reactive oxygen species. Oxidative stress also limited bacteriophage population diversity by favouring the selection of specialist bacteriophages with a narrower host range. Concomitantly, reactive oxygen species accelerated the evolution of bacterial resistance to bacteriophages and drove the fixation of genomic mutations in genes related to cell surface structures or located in mobile genetic elements. These results highlight that oxidative stress impacts the evolutionary dynamics between bacteria and bacteriophages with consequences for microbiota diversity and potential implications in the context of intestinal inflammation.
    Keywords:   Escherichia coli ; Phage; antagonistic coevolution; reactive oxygen species
    DOI:  https://doi.org/10.1093/ismejo/wrag090
  45. ACS Omega. 2026 Apr 07. 11(13): 20683-20690
      Skin wounds remain a clinical challenge, especially for burns and chronic wounds, and existing therapies seldom re-engage the rapid, scar-sparing repair programs observed in nature. Planarians are super-regenerators capable of rebuilding the entire organism from small fragments, and their extracellular vesicles might encode potent prorepair cues. But whether planarian-derived extracellular vesicles (EVs) can enhance mammalian skin healing is unknown. Therefore, we isolated EVs from a wild-type planarian flatworm collected in Sweden and evaluated their therapeutic activity in complementary wound models: a chicken chorioallantoic membrane assay and a human 3D skin model. In our models, planarian EVs significantly accelerated tissue regeneration and wound closure, and improved re-epithelialization and barrier integrity compared to controls. These data indicate that cross-species (xenogeneic) EVs from planarians carry bioactive factors capable of expediting cutaneous repair. Together, the results position planarian-derived EVs as a potential cell-free therapeutic strategy for burns and chronic wounds, motivating additional mechanistic and translational studies for clinical use.
    DOI:  https://doi.org/10.1021/acsomega.5c11592
  46. Wounds. 2026 Mar;38(3): S1-S20
       BACKGROUND: Effective debridement is a cornerstone of wound bed preparation and healing. Despite widespread recognition of its importance, practical guidance for selecting and sequencing debridement methods across diverse care settings remains limited.
    OBJECTIVE: To provide United States-based, patient-centered recommendations incorporating debridement into the continuum of wound management.
    METHODS: A 9-member panel composed of experts in vascular surgery, podiatric surgery, plastic and reconstructive surgery, general surgery, nursing, physical therapy, and basic science convened in Grapevine, Texas, in April 2025. Using nominal focus group methodology, these experts developed 20 draft statements from discussion transcripts and refined them through 2 survey rounds using a 5-point Likert scale. Interpanelist agreement was assessed using Kendall's W and Spearman rank correlation coefficient analysis.
    RESULTS: Seventeen consensus statements were finalized, reflecting high agreement (Kendall's W = 0.566). Core themes included matching debridement to wound goals and patient factors, adopting a dynamic escalation/de-escalation ("chutes and ladders") approach, and emphasizing communication, pain control, and diagnostic adjuncts. The panel stressed flexibility, clinician judgment, and patient-centered care when integrating debridement strategies across settings.
    CONCLUSION: This United States-based multidisciplinary consensus provides practical, patient-centered guidance for selecting and sequencing debridement methods across wound types and care settings, supporting clinicians to apply flexible, evidence-informed strategies to optimize wound bed preparation and healing outcomes.
    Keywords:  chronic wounds; clinical guidance; consensus statement; debridement; nominal focus group
    DOI:  https://doi.org/10.25270/wnds/25155
  47. Dermatol Ther (Heidelb). 2026 Apr 16.
       INTRODUCTION: Treat-to-target (T2T) strategies have been proposed to support decision-making in chronic plaque psoriasis care, but their use in Canadian clinical practice has not been well studied.
    METHODS: This retrospective chart review examined how Canadian T2T criteria are applied for adult patients with moderate-to-severe plaque psoriasis and whether treatment decisions reflect treatment target achievement in clinical practice. Charts from 438 adults who initiated or modified biologic therapy and completed two visits 3-8 months apart were included. Treatment target achievement at visit 2 was assessed using predefined major and minor criteria, which included Psoriasis Area and Severity Index (PASI), body surface area (BSA), Physician Global Assessment (PGA), and Dermatology Life Quality Index (DLQI) outcome measures.
    RESULTS: Of the 438 patients, 321 (73.3%) met the treatment target and 98.4% of these continued their current biologic therapy. Among the 117 patients who did not meet the treatment target, 48.7% of remained on their current biologic therapy. Treatment target achievement was associated with lower PASI, BSA, PGA, and DLQI scores. DLQI influenced treatment modification even when treatment targets were unmet. Switching between interleukin (IL)-17 and IL-23 inhibitors was the most frequent treatment modification strategy.
    CONCLUSION: Findings support the clinical value of Canadian T2T criteria, while highlighting the importance of shared decision-making. Many patients who did not meet treatment targets remained on their current biologic therapy, emphasizing the role of patient input, quality of life, and physician judgment. These results reinforce the importance of balancing treatment targets with individualized care in real-world plaque psoriasis management.
    Keywords:  Biologic therapy; Psoriasis; Real-world evidence; Treat-to-target; Treatment modification
    DOI:  https://doi.org/10.1007/s13555-026-01734-w
  48. Int J Mol Sci. 2026 Mar 25. pii: 2983. [Epub ahead of print]27(7):
      Periodontitis (PD) is a chronic inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. As one of the most prevalent chronic diseases, PD affects more than 743 million people globally, some with serious systemic health implications. Plaque accumulation constitutes the key driver of periodontitis, initiating host inflammatory cascades and compromising periodontal microbiome equilibrium. Conventional treatment methods, such as scaling and root planing, are limited by a constrained operative field, resulting in blind spots that impede the complete eradication of bacterial biofilms and the modulation of the inflammatory microenvironment. Therefore, employing new therapeutic strategies (e.g., drug delivery systems) is essential. This review focuses on local drug delivery systems for the treatment of PD, including fibers, strips and films, microspheres, gels, nanoparticles, and vesicle systems, to deliver drugs directly into the periodontal pockets, targeting inflammation and providing sustained antibacterial effects while reducing systemic side effects. The characteristics and clinical implications of each type of local drug delivery system are discussed, along with emerging technologies such as 3D printing and nanotechnology.
    Keywords:  anti-microbial therapy; chronic inflammation; local drug delivery systems; nanotechnology; periodontitis
    DOI:  https://doi.org/10.3390/ijms27072983
  49. Front Med (Lausanne). 2026 ;13 1809285
       Objective: This study aimed to evaluate the IWGDF/IDSA classification for prognostic stratification in diabetic foot infections (DFIs) and to develop and validate a clinical prediction model for individualized risk assessment.
    Methods: In this retrospective study of 300 patients with DFIs (2020-2024), infection severity was graded as Grade 2 (mild), 3 (moderate), 3(O) (moderate with osteomyelitis), or 4 (severe). We analyzed baseline characteristics, microbiological profiles, treatment responses, and performed time-to-event analyses for ulcer healing and limb salvage. A nomogram predicting 6-month non-healing risk was developed using Cox regression, with performance assessed by C-index and calibration. Subgroup and sensitivity analyses (including competing-risk models) were conducted to test robustness.
    Results: Higher infection grades correlated with worse glycemic control (HbA1c: 9.8% in Grade 4 vs. 8.1% in Grade 2), higher peripheral arterial disease (PAD) prevalence (64.3% vs. 22.4%), and a pathogen shift from Gram-positive cocci (87.2% in Grade 2) to Gram-negative bacilli (Pseudomonas aeruginosa 52.2%) and polymicrobial infections (60.9%) in Grade 4 (all p < 0.001). Kaplan-Meier analysis revealed a severity-dependent gradient in outcomes: median healing time prolonged from 6.0 weeks (Grade 2) to 18.0 weeks (Grade 4), while the 24-week cumulative amputation rate escalated to 66.7% in Grade 4. Osteomyelitis (Grade 3(O)) constituted a distinct high-risk subgroup, with outcomes approximating Grade 4. A nomogram incorporating infection grade, PAD, HbA1c ≥ 9%, and revascularization status demonstrated good discrimination (C-index 0.82, bootstrap-corrected 0.80) and calibration (Hosmer-Lemeshow p = 0.342), maintained in temporal validation (C-index 0.79). Subgroup analysis confirmed a significant interaction between infection grade and revascularization, with the greatest benefit in severe PAD patients (interaction p = 0.03). Sensitivity analyses, including competing-risk models, affirmed the robustness of the severity-outcome association.
    Conclusion: The IWGDF/IDSA classification effectively stratifies DFI patients by integrated metabolic, vascular, microbiological, and prognostic risk. Osteomyelitis warrants distinct management. The developed nomogram provides a validated tool for individualized risk prediction, facilitating early targeted intervention. These findings advocate for a severity-guided, multidisciplinary treatment paradigm to improve outcomes.
    Keywords:  IWGDF/IDSA classification; amputation; diabetic foot infection; diabetic foot ulcer; nomogram; osteomyelitis; risk prediction; survival analysis
    DOI:  https://doi.org/10.3389/fmed.2026.1809285
  50. AAPS PharmSciTech. 2026 Apr 15. pii: 180. [Epub ahead of print]27(3):
      Wound healing is a dynamic and highly coordinated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. However, chronic wounds such as diabetic ulcers, burn injuries, and infected wounds often fail to progress through the normal healing cascade due to persistent inflammation, bacterial infection, excessive oxidative stress, and impaired angiogenesis. Conventional wound dressings and topical therapies frequently show limited therapeutic efficacy because of poor adaptability to the wound microenvironment, inadequate drug retention, and uncontrolled drug release. In this context, thermo-sensitive polymeric networks have emerged as promising smart biomaterials for next-generation wound management. These materials exhibit temperature-responsive sol-gel phase transitions, enabling injectable or topical formulations that transform into stable hydrogels at physiological temperature, thereby ensuring conformal wound coverage, improved drug retention, and sustained therapeutic release. Thermo-responsive polymers such as poly(N-isopropylacrylamide), poloxamers, and chitosan-based derivatives have demonstrated significant potential in promoting wound repair through controlled delivery of antimicrobial agents, growth factors, natural bioactive compounds, and nanotherapeutics. Furthermore, the integration of nanomaterials and multifunctional components within thermo-responsive networks can enhance antibacterial activity, reduce inflammation, stimulate angiogenesis, and accelerate tissue regeneration. This review highlights recent advances in thermo-sensitive polymeric networks for wound management, focusing on material design strategies, therapeutic mechanisms, and biomedical applications. Additionally, current challenges, translational perspectives, and future opportunities for developing multifunctional and clinically adaptable thermo-responsive wound dressings are discussed.
    Keywords:  In situ gelation; Machine learning; Sol–gel transition; Thermo-sensitive polymers; Wound dressings
    DOI:  https://doi.org/10.1208/s12249-026-03423-5
  51. Diagnostics (Basel). 2026 Apr 01. pii: 1055. [Epub ahead of print]16(7):
      Background/Objectives: Accurate and reproducible wound measurement is essential for monitoring healing and guiding treatment decisions. Conventional ruler-based techniques are prone to geometric overestimation and operator variability. This study evaluated the accuracy and reproducibility of the MolecuLightDX wound imaging device for measuring wound surface area and depth compared with ruler-based measurements and ground truth digital photography methods. Methods: This investigation comprised two companion studies: a prospective, paired, multicenter clinical study comparing MolecuLightDX measurement with the ruler method against an image-based ground truth, and a bench and clinical validation of the AutoDepth feature against a calibrated three-dimensional optical scanner. The area of study included 17 benchtop wound models and enrolled 27 patients (33 wounds; area range: 0.56-23.04 cm2) across two wound care centers, and the AutoDepth study included 17 benchtop wound models and 34 clinical wounds (depth range: 0.06-4.13 cm). Accuracy, intra- and inter-user variability, and agreement were assessed using the mean percentage error (MPE), coefficient of variation (CV), intraclass correlation coefficients (ICC), and Bland-Altman analysis. Results: The device demonstrated high accuracy and reproducibility for both wound surface area and depth measurements compared with ruler-based and ground truth digital photography methods. The MPE for surface area was <10%, representing a tenfold improvement over ruler estimation (77.9%). For wound area, intra- and inter-user CVs were <10%, and for depth, ICCs were ≈0.99. Conclusions: The MolecuLightDX device provides accurate and consistent wound area and depth measurements across diverse wound types, demonstrating superior accuracy and reproducibility compared with conventional ruler-based methods and supporting its integration into wound assessment workflows.
    Keywords:  AutoDepth; MolecuLightDX; arterial ulcer; chronic wounds; diabetic foot ulcer; digital planimetry; pressure injury; traumatic wound; venous leg ulcer; wound measurement
    DOI:  https://doi.org/10.3390/diagnostics16071055
  52. bioRxiv. 2026 Apr 09. pii: 2026.04.09.717387. [Epub ahead of print]
      Contemporary antibiotic treatment almost solely considers the Minimum Inhibitory Concentration (MIC) when deciding to employ an antibiotic, often overlooking the critical role of host immunity. Using Galleria mellonella and a virulent strain of Staphylococcus aureus , we investigate the infection dynamics and treatment outcomes of antibiotics of different classes-including antibiotics to which the bacteria are resistant-and a lytic bacteriophage. Surprisingly, we find that the host's ability to control bacterial density and survive infection does not depend on the specific type of antimicrobial agent nor the bacteria's susceptibility to it. Our results demonstrate that the innate immune system is the primary factor in therapeutic success, capable of clearing even highly resistant infections, such as those involving beta-lactamase-producing or ribosomal mutant-resistant strains. These findings challenge the traditional antibiotic-centric view of infection outcomes and emphasize the need to account for host-pathogen-drug interactions beyond simple MIC measurements when designing clinical treatment regimens.
    DOI:  https://doi.org/10.64898/2026.04.09.717387
  53. J Dent (Shiraz). 2026 Mar;27(4): 1-12
       Background: Artificial intelligence (AI) powered technologies can help detect Candida albicans (C. albicans) infections, which are a public health challenge due to increasing incidence rates and conventional therapy resistance.
    Purpose: This review explores recent advancements, methodologies, and clinical implications in the AI-driven microscopic detection of C. albicans.
    Materials and Method: A literature search was conducted across multiple databases, including PubMed, Scopus, Embase, Web of Science, and Google Scholar. Following a thorough review of the retrieved articles, 7 studies were selected for inclusion in this review.
    Results: This review analyzed 7 studies that employed AI and machine learning (ML) to detect the presence of C. albicans. The most commonly used dataset for detecting C. albicans through AI was microscopic images. Two studies employed time-lapse microscopy, and another study used the microorganism's smell fingerprint or volatile organic compounds with an impressive accuracy of 97.70%. The accuracy of detecting C. albicans through AI using microscopic images ranged from 63% to 100% depending on the model used.
    Conclusion: AI can improve the detection of C. albicans infections. It can enhance the accuracy, speed, and efficiency of detection, providing clinicians with invaluable support in identifying infections earlier, optimizing treatment strategies, and ultimately improving patient outcomes.
    Keywords:   Artificial Intelligence; Candida albicans; Deep Learning; Machine Learning
    DOI:  https://doi.org/10.30476/dentjods.2025.104629.2540
  54. Nurs Outlook. 2026 Apr 14. pii: S0029-6554(26)00092-8. [Epub ahead of print]74(3): 102769
       BACKGROUND: Clinical rotations are a cornerstone of prelicensure nursing education, yet they remain organized, regulated, and evaluated primarily through fixed requirements for time spent in clinical settings. Despite widespread reliance on clinical hours to signal practice readiness, the empirical evidence supporting specific hour thresholds is limited. At the same time, nursing education is increasingly adopting competency‑based education (CBE).
    PURPOSE: This paper aims to reframe what counts as the primary currency of clinical preparation-from hours completed to competencies demonstrated-and to examine the implications of this shift for practice readiness, workforce sustainability, and educational equity.
    METHODS: We synthesize empirical and conceptual literature on clinical hours, simulation‑based education, and competency‑based and experiential learning. We also analyze historical, regulatory, and operational factors that have contributed to the persistence of time‑based clinical requirements.
    DISCUSSION: Drawing on principles of CBE and experiential learning, we describe several promising pathways for rethinking clinical education, including strategic use of simulation, individualized preceptorships, electronic competency tracking systems, experiential portfolios, and evolving faculty roles. We discuss the feasibility, tradeoffs, and equity considerations associated with these approaches, as well as the regulatory challenges that must be addressed for competency‑driven models to scale.
    CONCLUSION: Reorienting clinical education around documented competence rather than time alone offers a more transparent, adaptable, and equitable framework for judging readiness for practice. Shifting the focus from hours accrued to competencies demonstrated better aligns nursing education with contemporary health care delivery and supports intentional assessment, remediation, and innovation in clinical preparation.
    Keywords:  Clinical rotations; Competency-based education; Simulation
    DOI:  https://doi.org/10.1016/j.outlook.2026.102769