Deciphering the resistome of the widespread P. aeruginosa ST175 international high-risk clone through whole genome sequencing

Whole genome sequencing (WGS) was used for the characterization of the, frequently extensively-drug resistant (XDR), P. aeruginosa high-risk clone ST175. A total of eighteen ST175 isolates recovered from 8 different Spanish hospitals were analyzed; four isolates from four different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with the two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance and horizontally-acquired genes were explored using online databases. The resistome of ST175 was mainly determined by mutational events, with resistance traits common to all or nearly all of the strains, including specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas such as a streptomycin resistance aadA13 gene detected in all four isolates from France and in the 2 isolates from the Cantabria region or a glpT mutation conferring fosfomycin resistance detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting among them were those in genes encoding PBPs (PBP1A, PBP3 and PBP4). Thus, these results provide valuable information for understanding the genetic basis of resistance and the dynamics of dissemination and evolution of high-risk clones.