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

ABSTRACT: 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

SUBMITTER: Fan L 

PROVIDER: S-EPMC12782431 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature