bims-ainimu 2026-01-04 papers

Issue of 2026–01–04
two papers selected by
Pedro Escoll Guerrero, Institut Pasteur

Nucleic Acids Res. 2025 Nov 26. pii: gkaf1371. [Epub ahead of print]53(22):

3'UTR-derived small RNA couples acid resistance to metabolic reprogramming of Salmonella within macrophages.

Takeshi Kanda, Fang Liu, Hoda Kooshapour, Sarah Reichardt, Maolin Wang, Philippe Icyishaka, Nozomu Obana, Alexander J Westermann, Yanjie Chao, Masatoshi Miyakoshi.

Acid resistance is crucial for enterobacteria to withstand host acidic environments during infection, including the gastrointestinal tract and macrophage phagosomes. A key acid resistance mechanism of the facultative intracellular pathogen Salmonella is the expression of the arginine decarboxylase AdiA. While AdiA confers acid resistance via an H+-consuming reaction, we discover that the 3'-untranslated region (UTR) of adiA mRNA is processed by RNase E into a regulatory small RNA, AdiZ. Through RNA-RNA interactome profiling and transcriptomic analysis, followed by in vitro structural probing and in vivo validations, we demonstrate that AdiZ directly base-pairs with and negatively regulates ptsG, pykF, and dmsA mRNAs involved in glucose uptake, glycolysis, and anaerobic respiration, respectively. Intriguingly, AdiZ is induced and facilitates Salmonella survival within macrophages, where acidic and hypoxic stresses prevail. Thus, simultaneous expression of AdiA and AdiZ from a single mRNA ties arginine-dependent acid resistance to metabolic reprogramming of Salmonella in the host intracellular niches.

DOI: https://doi.org/10.1093/nar/gkaf1371

PLoS Pathog. 2025 Dec 31. 21(12): e1013304

Pp6-Pfkfb1 axis modulates intracellular bacterial proliferation by orchestrating host-pathogen metabolic crosstalk.

Li Fan, Yang Sun, Fangzhou Lou, Zilong Fang, Wengxiang Ding, Xiangxiao Li, Yan Li, Qingqing Shen, Siyu Deng, Jihuan Liang, Fengjiao Zhang, Sibei Tang, Zhikai Wang, Xiaojie Cai, Jiajia Tong, Zhenyao Xu, Jing Zou, Qing Yang, Honglin Wang.

Intracellular bacterial pathogens exhibit heterogeneous replication rates within host macrophages, but the mechanisms by which they manipulate host factors for survival remain incompletely understood. Using a fluorescence-dilution reporter system in Salmonella Typhimurium (Salmonella)-infected macrophages, we found that Protein Phosphatase 6 (Pp6) was downregulated in macrophages harboring growing bacteria. Conditional knockout of Pp6 elevated host susceptibility to Salmonella-mediated lethality due to compromised antimicrobial defenses. MicroRNA-31 (miR-31) was identified as a negative regulator of Pp6, and its conditional ablation enhanced bacterial clearance. Yeast two-hybrid screening identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 (Pfkfb1), a metabolic regulator, as a substrate of Pp6. Pp6 deficiency resulted in significantly elevated expression of Pfkfb1, which was highly expressed in macrophages containing replicating Salmonella. Pfkfb1 deletion restricted bacterial proliferation by promoting nitric oxide (NO) production while concurrently suppressing arginase-1 (Arg-1) expression and impairing arginine metabolism in macrophages. Collectively, these results establish the Pp6-Pfkfb1 axis as a key regulator of host metabolic adaptation and intracellular bacterial survival, offering potential therapeutic targets against multidrug-resistant pathogens.

DOI: https://doi.org/10.1371/journal.ppat.1013304