Molecular blueprint of uropathogenic Escherichia coli virulence provides clues toward the development of anti-virulence therapeutics

摘要

Effective treatment of many infections has progressively become more difficult due to the worldwide increase in antimicrobial resistance and the paucity of new antimicrobial development. Urinary tract infections (UTIs) are among the most common infections afflicting primarily women, and often resulting in recurrences or chronic infections that require frequent retreatment or long-term prophylaxis with antimicrobials. Either approach exposes patients to frequent antimicrobial use and its consequences. This is leading to a serious medical impasse requiring innovative therapeutic strategies. Uropathogenic Escherichia coli (UPEC) are the predominant UTI causative agent. This article highlights work that we have performed, distinguishing the contribution of two UPEC virulence determinants, the QseBC two-component system and type 1 pili, in pathogenesis. We discuss our findings on the impact of QseC disruption alone and in the presence of mannosides, orally bioavail-able small-molecular weight inhibitors of the FimH adhesin that are highly efficacious in the treatment of UTI in a murine model. Our work provides insights toward the development of alternative therapeutics for UTIs.