Insight into phylogenomic bias of bla VIM-2 or bla NDM-1 dissemination amongst carbapenem resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa are ubiquitous opportunistic pathogens that combine intrinsic and acquired multidrug resistance phenotypes. Carbapenem resistance has been expanding in this species, due to different types of acquired genes. In this study, we hypothesised that the spread of carbapenem-resistance among P. aeruginosa is influenced by phylogenomic features, being distinct for different genes. To test this hypothesis, we compared the genomes of P. aeruginosa harbouring blaVIM-2 or blaNDM-1 genes. The gene blaVIM-2 was selected because, although frequent, it is almost restricted to this species and blaNDM-1 due to its wide interspecies distribution. A group of genomes harbouring the genes blaVIM-2 (n=116) or blaNDM-1 (n=27), available in the GenBank, was characterized based on core phylogenomic analysis, functional categories in the accessory genome and mobile genetic elements flanking the selected genes. Most blaVIM-2 gene hosts belonged to multilocus sequence types (ST) ST111 (n=32/116) and ST233 (n=27/116) and were reported in Europe (n=75/116). The blaNDM-1 gene hosts were distributed by different ST (ST38, ST773, ST235, ST357, ST654), frequently from Asia (n=11/27). Significant differences in the prevalence of functional protein/enzyme annotations per number of accessory genomes were observed between blaVIM-2 + or blaNDM-1 +. The blaVIM-2 gene was frequently inserted in Tn402-like and Tn21 transposons family and rarely in IS6100, while blaNDM-1 gene was preferentially flanked by ISAba125 and bleMBL genes or associated with IS91 insertion sequence. The hypothesis that carbapenem resistance gene acquisition is not random among phylogenomic lineages was confirmed, suggesting the importance of phylogeny in the dissemination of antibiotic resistance genes.