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

Abstract

Serratia marcescens, 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 S. marcescens infections. This work identifies urea-induced lactonase of Serratia (UilS), a lactonase encoded in the S. marcescens 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 uilS 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 Pseudomonas aeruginosa. We found that LuxR regulates uilS 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 S. marcescens, 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 S. marcescens that involves UilS, indicating its importance in the interspecies interaction of Serratia. Finally, we found that a uilS mutant strain displays attenuated colonization in a mouse model of catheter-associated urinary tract infection. uilS is present in clinical but absent in environmental isolates, suggesting an evolutionary adaptation to host-specific selective pressures.