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
Pseudomonas aeruginosa is an opportunist and versatile organism responsible for infections mainly in immunocompromised hosts. This pathogen has high intrinsic resistance to most antimicrobials. P. aeruginosa AG1 (PaeAG1) is a Costa Rican high-risk ST-111 strain with resistance to multiple antibioti...
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|Summary:||Pseudomonas aeruginosa is an opportunist and versatile organism responsible for infections mainly in immunocompromised hosts. This pathogen has high intrinsic resistance to most antimicrobials. 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 VIM-2 and IMP-18 metallo-β-lactamases (MBLs). These genes are harbored in two class 1
integrons located inone out of the 57 PaeAG1 genomic islands. However, the genomic context associated to these
determinants in PaeAG1 and other P. aeruginosa strains is unclear. Thus, we first assessed the transcriptional
activity of VIM-2 and IMP-18 genes when exposed to imipenem (a carbapenem) by RT-qPCR. To select related
genomes to PaeAG1, we implemented a pan-genome analysis to define and up-date the phylogenetic relationship
among complete P. aeruginosa genomes. We also studied the PaeAG1 genomic islands content in the related
strains and finally we described the architecture and possible evolutionary steps of the genomic regions around
the VIM-2- and IMP-18-carrying integrons.
Expression of VIM-2 and IMP-18 genes was demonstrated to be induced after imipenem exposure. In a subsequent comparative genomics analysis with 211 strains, the P. aeruginosa pan-genome revealed that complete
genome sequences are able to separate clones by MLST profile, including a clear ST-111 cluster with PaeAG1. The
PaeAG1 genomic islands were found to define a diverse presence/absence pattern among related genomes.
Finally, landscape reconstruction of genomic regions showed that VIM-2-carrying integron (In59-like) is an oldacquaintance element harbored in the same known region found in other two ST-111 strains. Also, PaeAG1 has
an exclusive genomic region containing a novel IMP-18-carrying integron (registered as In1666), with an
arrangement never reported before. Altogether, we provide new insights about the genomic determinants
associated with the resistance to carbapenems in this high-risk P. aeruginosa using comparative genomics.|