Integrative conjugative elements of SXT/R391 family in Proteus mirabilis and its correlation with resistance, mutagenesis and conjugation

Abstract

Proteus mirabilis is a bacterium that causes catheter-associated urinary tract infections (CAUTIs) that has its clinical importance associated with prolonged catheterizations. Due to its beta-lactam-sensitive nature, the emergence of resistance to this class of antibiotics led to the identification of the integrative conjugative elements (ICEs) of the SXT/R391 family, which carried such resistance genes. ICEs have genes that regulate the transfer mechanism itself, as well as several other conserved genes of unknown or apparently non-essential functions for the transfer process. Among these conserved genes is the rumAB operon, a homolog of E. coli umuDC that encodes a DNA polymerase from the Y family, characterized by the high error rate. The regulation of rumAB expression is under control of the SOS response, the same regulation controlling the conjugative functions of ICE. This response is induced when DNA damage is caused, for example, by exposure to antibiotics. By inducing the transionic polymerases, the SOS response leads to the transient increase in the mutation rate. Mutations in the chromosome, in turn, may lead to the emergence of resistance to certain antimicrobials such as fosfomycin and ciprofloxacin.In the genome of P. mirabilis, there are no homologues of these translesion polymerases, except in those lines harboring the ICE SXT/R391, which has rumAB with it. Therefore, in this project, in addition to identifying possible resistance genes carried by these elements in Brazilian clinical isolates, we will perform functional analysis of rumAB translesion polymerase, analyzing their role in mutagenesis processes and in the maintenance and conjugation of ICEs. (AU)