Urea regulation in Serratia marcescens and its role in quorum sensing and inter-bacterial competition

TUTTOBENE, MARISEL ROMINA; RAMÍREZ, MARÍA SOLEDAD; VESCOVI, ELEONORA GARCÍA

Los Cocos

Congreso; SAMIGE 2022; 2022

Serratia marcescens belongs to the family of Enterobacteriaceae and could be isolated from a wide variety of environmental niches, from water and soil to air. In addition to its ecological ubiquity, S. marcescens is an emerging health-threatening nosocomial pathogen. In recent years, numerous outbreaks of strains carrying multidrug resistance and a high incidence have been reported. In 2017, the World Health Organization declared S. marcescens, along with other Enterobacteriaceae, a priority research target to develop alternative antimicrobial strategies given the high frequency of clinical isolates resistant to carbapenems. Our laboratory study model is the S. marcescens RM66262 strain, a non-pigmented clinical isolate from a patient with urinary tract infection (UTI) from a hospital in Rosario, Argentina. The major component of urine is urea, which has been shown to repress the detection of quorum sensing in Pseudomonas aeruginosa. In our laboratory, we carried out a transcriptional analysis of S. marcescens exposed to urea. The RNA-seq analysis showed that urea is a regulatory signal that affects the expression of numerous genes in Serratia, including a subset related to the metabolism and detection of quorum sensing molecules. Among these genes, the expression of a putative lactonase was increased by the presence of urea in the culture medium. Phenotypic assays confirmed that this gene encodes for a quorum quenching protein with cytoplasmic activity, and has the ability to degrade acyl-homoserine lactones (AHL) from Serratia and other bacteria such as P. aeruginosa. Furthermore, our results indicate that S. marcescens produced AHL under static growth conditions (quorum sensing), while lactonase activity occurred under shaking conditions (quorum quenching) when exposed to urea treatment. The integrity of the luxR gene and AHL are necessary for urea-mediated induction to be verified. Finally, inter-bacterial competition assays between Serratia and P. aeruginosa show that our strain behaves as a more aggressive attacker in the presence of urea (Serratia was able to diminish 3-fold P. aeruginosa CFU count). We can conclude that urea is a signal that modulates the expression of quorum sensing molecules, as well as inter-bacterial competition capacity.