An IncP-2 plasmid sublineage associated with dissemination of <i>bla</i> _IMP-45 among carbapenem-resistant <i>Pseudomonas aeruginosa</i>

Abstract

IMP-45, a variant of IMP-9, is one of the dominant metallo-β-lactamases (MBLs) in clinical carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) isolates in China. The aim of this study was to investigate the distribution and mechanism of dissemination of <i>bla</i>_IMP-45. MBL genes were detected by PCR in 173 non-duplicate CRPA isolates collected from Hospital HS in Shanghai and 605 <i>P. aeruginosa</i> isolates from a multicenter surveillance of <i>bla</i>_IMP-45 in China. In total, 17 IMP-45-producers (14 from Hospital HS and 3 from other hospitals) were identified. Molecular typing identified an outbreak of 11 IMP-45-producing ST508 CRPA in the ICU of Hospital HS. Conjugation assays and whole genome sequencing were conducted among IMP-45-producers. Genomic comparison revealed that 16 <i>bla</i>_IMP-45-carrying plasmids (9 from this study and 7 from GenBank) shared a similar backbone with IncP-2 <i>bla</i>_IMP-9-carrying plasmid pOZ176 but lacked <i>repA</i>-<i>oriV</i>-<i>parAB</i> region. <i>repA2</i> gene was presented in pOZ176, <i>bla</i>_IMP-45-carrying plasmids (17 from this study and 7 from GenBank) and 15 megaplasmids from GenBank. Phylogenetic analysis of <i>repA2</i> showed that most <i>bla</i>_IMP-45-carrying plasmids were clustered into a sublineage separate from the one containing pOZ176. This IncP-2 plasmid sublineage contributed to the dissemination of <i>bla</i>_IMP-45 among genetically diverse <i>P. aeruginosa</i> and recruited multiple resistance genes during its evolution.