From Pan-genome to the Genomic Context of the Two Integrons of ST-111 Pseudomonas Aeruginosa AG1: A VIM-2-carrying Old-acquaintance and a Novel Imp-18-carrying Integron

Abstract

Background Pseudomonas aeruginosa is an opportunist and versatile organism responsible for infections among immunocompromised hosts. This pathogen has high intrinsic resistance to most antimicrobials, including critical strains due to resistance to carbapenems, a last-resort antibiotic. P. aeruginosa AG1 (PaeAG1) is a Costa Rican high-risk ST-111 strain with resistance to multiple antibiotics, including carbapenems due to the activity of both VIM-2 and IMP-18 metallo-β-lactamases (MBLs). These genes are harbored in two class 1 integrons, belonging to one out of the 57 PaeAG1 genomic islands. However, the genomic context related to these determinants in PaeAG1 and other P. aeruginosa strains is unclear. Thus, we implemented a comparative genomic approach to define and up-date the phylogenetic relationship among complete P. aeruginosa genomes using a pan-genome analysis. We also studied the PaeAG1 genomic islands content in other strains and the architecture of genomic regions around the VIM-2- and IMP-18-carrying integrons. Results With 211 strains, the up-dated P. aeruginosa pan-genome revealed that complete genome sequences are able to separate clones by MLST profile (ST), including a clear ST-111 cluster with PaeAG1. The PaeAG1 genomic islands were found to define a diverse presence/absence pattern among related genomes, but content was related to phylogenetic relationships. Finally, landscape reconstruction of specific genomic regions showed that VIM-2-carrying integron (In59-like) is an old-acquaintance element harbored in a known genomic region completely found in other two ST-111 strains. In addition, PaeAG1 has an exclusive genomic region containing a novel IMP-18-carrying integron (registered as In1666), with an arrangement never reported before. Conclusions We provide new insights about the genomic determinants associated with the resistance to carbapenems in the high-risk PaeAG1 using comparative genomics. With the pan-genome analysis and the comparison of PaeAG1 genomic islands in other strains, it was possible to describe the genomic landscape of the two MBLs-carrying integrons, including an old-acquaintance element carrying VIM-2 and a new IMP-18-carrying integron.

A first perturbome of Pseudomonas aeruginosa: Identification of core genes related to multiple perturbations by a machine learning approach

“…We reported this isolated in 2015 [58] and it is a Priority 1 organism [59] because it is resistant to carbapenems, a last-resort antibiotic. We assembled the genome using Illumina and Nanopore sequencing [13], revealing the genomic features including two integrons, which were studied in detail in another work [60]. Proteomic profiles after exposure to antibiotics have been also studied [61].…”