UREA MODULATES THE TRANSCRIPTIONAL EXPRESSION OF THE Serratia marcescens METALLOPROTEASE PRTA

GARCÍA VÉSCOVI, ELEONORA; MOLINO, MV

Evento virtual debido a la pandemia 2020

Congreso; LVI SAIB Meeting ? XV SAMIGE Meeting; 2020

SAIB-SAMIGE (Congreso conjunto)

Serratia marcescens belongs to the Enterobacteriaceae family and can be isolated from a wide variety of environmental niches. In addition, S. marcescens is an emergent health threatening pathogen, associated with urinary and respiratory tract as well as wound and eye infections, endocarditis, osteomyelitis, meningitis, and septicemia. In the last years, multi-drug resistance strains outbreaks and high incidence in intensive and neonatal care units are increasingly being reported. The World Health Organization recently declared S. marcescens, together with other enterobacteria, a research priority target to develop alternative antimicrobial strategies given the high frequency of carbapenems resistant clinical isolates. Despite its clinical prevalence, the factors and mechanisms that contribute to Serratia pathogenesis remain unclear. Our study model is based on S. marcescens RM66262 strain. This strain is a nonpigmented clinical isolate from a patient with urinary tract infection (UTI) from the Bacteriology Service of the Facultad de Ciencias, Bioquímicas y Farmacéuticas of the Rosario National University, Rosario, Argentina. UTIs are one of the most common types of bacterial infections in humans. Because the majority of UTIs develop via the ascending route through the urethra, bacteria are subjected to periodic environmental stress from human urine and face various inorganic ions and osmolytes such as urea. Thus, we hypothesized that urea might act as a signal that triggers Serratia adaptive responses to face the challenge that represents the colonization of the urinary tract. In fact, Proteus mirabilis, an organism notorious for causing catheter-associated urinary tract infections and urinary stones, activates transcription of genes required for the synthesis of urease structural and accessory proteins in the presence of urea. Despite this, little is known about other responses of bacteria to urea. In line with our hypothesis, our results show that urea transcriptionally represses the expression of PrtA, the major Serratia secreted metalloprotease. In addition, the SDS-PAGE analysis of the extracellular protein pattern from S. marcescens grown in the presence of urea showed a drastic change in the relative abundance of numerous secreted proteins, in comparison to the medium without urea. No studies have explored the relative contributions of urea to S. marcescens transcriptional responses in urine, and the regulatory mechanisms that mediate these changes in gene expression are not known yet. It is tempting to argue that urea might act as a signal that induces Serratia gene reprogramming required for transition between extra and intra-host niches. To further understand this, a strategy to identify factor(s) responsible for recognizing and mediating the repressive action of urea on prtA transcriptional activity is currently under way in the lab.