Regulation of E. coli intestinal colonization by the PhoQ/PhoP two-component system

• Applicant: Dr. Jing Yuan
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576734961

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections, accounting for over 150 million cases worldwide each year. UPEC cells typically reside in the human gut, establishing a reservoir. Through fecal shedding, they spread to the periurethral area or vagina, enter the urethra, ascend the urinary tract, and cause infection. To promote intestinal colonization and increase transmissibility, UPEC may have evolved regulatory pathways that are shared with commensal E. coli strains. The PhoQ/PhoP two-component signaling system recognizes signature molecules in the mammalian gut and regulates genes involved in virulence and stress responses. Interestingly, although studies of PhoQ/PhoP have focused almost exclusively on virulence regulation, virulence genes represent only a small fraction of the PhoP regulon. Whether this two-component system also influences E. coli gut colonization is unknown. Our preliminary data show that E. coli strains with altered PhoQ/PhoP activity have reduced colonization compared to the wild type, likely due to changes in interactions with mammalian cells and the fitness of the E. coli strains. The UPEC and commensal E. coli cells with elevated PhoQ activity have higher levels of fimbriae proteins and display increased attachment to mucus-producing epithelial cells in vitro. Furthermore, we have identified a putative PhoP binding site in the promoter region of the fimbriae operon to which phosphorylated PhoP appears to bind in electrophoretic mobility shift assays. These preliminary data strongly suggest that the PhoQ/PhoP two-component system is involved in the regulation of E. coli intestinal colonization. To elucidate the mechanism of this regulation, we plan to systematically investigate the impact of PhoQ/PhoP on i) fimbriae expression, ii) the attachment of E. coli to mammalian cells, iii) the fitness of E. coli, and the distribution of this regulatory pathway. Our findings will provide a deeper understanding of the colonization process of commensal E. coli and UPEC. We will gain insight into the regulation of colonization by PhoQ/PhoP, which may help in the development of new-generation antimicrobials to prevent urinary tract infections and reduce the reliance on antibiotics for treatment.

• DFG Programme: Research Grants