Emergence and Expansion of a Carbapenem-Resistant Pseudomonas aeruginosa Clone Are Associated with Plasmid-Borne <i>bla</i> _KPC-2 and Virulence-Related Genes

Abstract

<i>Pseudomonas aeruginosa</i> is a major opportunistic pathogen and one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of severe infections caused by <i>P. aeruginosa</i> However, our recent surveillance demonstrated that the prevalence of carbapenem-resistant <i>P. aeruginosa</i> (CRPA) reached 38.67% in Zhejiang, China. By analyzing CRPA isolates collected from patients from 2006 to 2018, we found that 33% of CRPA isolates carried the gene <i>bla</i> _KPC-2, which conferred high-level resistance to carbapenems and other β-lactams. In particular, a CRPA clone, ST463 (sequence type 463), emerged and has become the predominant CRPA clone among the population. Genome sequencing demonstrated that ST463 expansion was associated with plasmid-borne <i>bla</i> _KPC-2 The mobile element flanking <i>bla</i> _KPC-2, the type IV secretion system, and the successful expansion of clone ST463 might have further favored <i>bla</i> _KPC-2 spread in <i>P. aeruginosa</i> Molecular clock analysis dated the emergence of clone ST463 to around 2007. Genome-wide association analysis showed that 567 genes were associated with clone ST463, including several known virulence genes related to the biosynthesis of lipooligosaccharide (LOS) O-antigens and exotoxin. These findings indicate that ST463 is expanding with plasmid-borne <i>bla</i> _KPC-2 and virulence-related genes in nosocomial infections, and close surveillance should be undertaken in the future.<b>IMPORTANCE</b> Health care-associated infections, also known as nosocomial infections, are the most frequent adverse events in health care delivery worldwide, causing high rates of morbidity and mortality and high health care costs. <i>Pseudomonas aeruginosa</i> is one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of its severe infections. However, the prevalence of carbapenem-resistant <i>P. aeruginosa</i> (CRPA) has been increasing rapidly in recent years, and our surveillance demonstrated that the prevalence of CRPA reached 38.67% in Zhejiang, China. Genome sequencing of CRPA isolates over a decade showed that a CRPA clone (ST463) emerged recently. The clone is highly resistant to β-lactams, including carbapenems, and fluoroquinolones. Genome-wide association analysis showed that the clone expanded with virulence-related genes and the plasmid-borne carbapenem-resistant gene <i>bla</i> _KPC-2 These findings are of significant public health importance, as the information will facilitate the control and minimization of CRPA nosocomial infections.