Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection.

摘要: Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), are one of the leading bacterial due to their high frequency and rate recurrence. Both type 1 pilus adhesive organelles (fim) QseC sensor kinase have been implicated in UPEC virulence during UTI individually reported be promising drug targets. Deletion qseC leads pleiotropic effects unregulated activation cognate response regulator QseB, influencing conserved metabolic processes diminishing expression genes, including pili. Here, we discern pilus-dependent -independent that contribute attenuation a deletion mutant murine model experimental UTI. We show although ΔqseC restored for regains ability colonize host initiate acute infection up 16 h postinfection, it is rapidly outcompeted when coinoculated with wild-type strain. As result, this strain has diminished capacity establish chronic infection. A prophylactic oral dose FimH small-molecular-weight antagonist (ZFH-02056) further reduced Thus, loss significantly enhances efficacy ZFH-02056. Collectively, our work indicates pili become critical different stages, dual targeting these factors an additive effect on ablating virulence.