Unraveling the role of UilS, a urea-induced acyl-homoserine lactonase that enhances fitness, interbacterial competition, and urinary tract infection.

UNLABELLED

, a member of the Enterobacteriaceae family, is an opportunistic human pathogen and a frequent cause of urinary tract infections. Clinical isolates often exhibit resistance to multiple antibiotics, posing challenges for successful treatment. Understanding its pathogenic mechanisms is crucial for elucidating new potential targets to develop effective therapeutic interventions and manage infections. This work identifies rea-nduced actonase of (UilS), a lactonase encoded in the RM66262 strain isolated from a patient with a urinary tract infection. The study explores the bacterium's response to urea, a major component of urine, and its impact on expression. We found that UilS degrades acyl-homoserine lactones (AHL) autoinducers traditionally associated with quorum sensing mechanisms. Surprisingly, UilS is able to degrade self and non-self AHL, exhibiting quorum-quenching activity toward . We found that LuxR regulates expression that is enhanced in the presence of AHL. In addition, urea-dependent induction of UilS expression is controlled by the transcriptional response regulator CpxR. UilS confers fitness advantage to , especially in the presence of urea, emphasizing the adaptive plasticity of strains to modulate gene expression based on environmental signals and population density. We also discovered a novel bacterial killing capacity of that involves UilS, indicating its importance in the interspecies interaction of . Finally, we found that a mutant strain displays attenuated colonization in a mouse model of catheter-associated urinary tract infection. is present in clinical but absent in environmental isolates, suggesting an evolutionary adaptation to host-specific selective pressures.

IMPORTANCE

This work reveals the acyl-homoserine lactonase rea-nduced actonase of as a novel virulence factor of , unraveling a potential target to develop antimicrobial strategies and shedding light on the complex regulatory network governing pathogenicity and adaptation to host environments.