Insight into phylogenomic bias of blaVIM-2 or blaNDM-1 dissemination amongst carbapenem resistant Pseudomonas aeruginosa

Objectives: Pseudomonas aeruginosa (P. aeruginosa) are ubiquitous opportunistic pathogens that combine intrinsic and acquired multidrug resistance phenotypes. Due to different types of acquired genes, carbapenem resistance has been expanding in this species. This study hypothesised that the spread of carbapenem resistance among P. aeruginosa is influenced by phylogenomic features, being distinct for different genes. Methods: To test this hypothesis, the genomes of P. aeruginosa harbouring bla _VIM-2 or bla _NDM-1 genes were compared. The bla _VIM-2 gene was selected because, although frequent, it is almost restricted to this species and bla _NDM-1 gene due to its wide interspecies distribution. A group of genomes harbouring the genes bla _VIM-2 (n = 116) or bla _NDM-1 (n = 27), available in GenBank, was characterised based on core phylogenomic analysis, functional categories in the accessory genome and mobile genetic elements flanking the selected genes. Results: Most bla _VIM-2 gene hosts belonged to multilocus sequence types (ST) ST111 (n = 32 of 116) and ST233 (n = 27 of 116) and were reported in Europe (n = 75 of 116). The bla _NDM-1 gene hosts were distributed by different STs (ST38, ST773, ST235, ST357 and ST654), frequently from Asia (n = 11 of 27). Significant differences in the prevalence of functional protein/enzyme annotations per number of accessory genomes were observed between bla _VIM-2+ and bla _NDM-1+. The bla _VIM-2 gene was frequently inserted in the Tn402-like and Tn21 transposons family and rarely in IS6100, while bla _NDM-1 gene was preferentially flanked by ISAba125 and ble _MBL genes or associated with IS91 insertion sequence. Conclusion: 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.