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

ABSTRACT: Pseudomonas aeruginosa 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 P. aeruginosa However, our recent surveillance demonstrated that the prevalence of carbapenem-resistant P. aeruginosa (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 bla _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 bla _KPC-2 The mobile element flanking bla _KPC-2, the type IV secretion system, and the successful expansion of clone ST463 might have further favored bla _KPC-2 spread in P. aeruginosa 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 bla _KPC-2 and virulence-related genes in nosocomial infections, and close surveillance should be undertaken in the future.IMPORTANCE 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. Pseudomonas aeruginosa 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 P. aeruginosa (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 bla _KPC-2 These findings are of significant public health importance, as the information will facilitate the control and minimization of CRPA nosocomial infections.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8269210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly bla NDM-1 and bla KPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes bla NDM-1 and bla KPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the bla NDM-1 and virulence genes and a bla KPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.

Project description:While conducting genomic surveillance of carbapenemase-producing Enterobacteriaceae (CPE) from patient colonisation and clinical infections at Birmingham's Queen Elizabeth Hospital (QE), we identified an N-type plasmid lineage, pQEB1, carrying several antibiotic resistance genes, including the carbapenemase gene bla KPC-2. The pQEB1 lineage is concerning due to its conferral of multidrug resistance, its host range and apparent transmissibility, and its potential for acquiring further resistance genes. Representatives of pQEB1 were found in three sequence types (STs) of Citrobacter freundii, two STs of Enterobacter cloacae, and three species of Klebsiella. Hosts of pQEB1 were isolated from 11 different patients who stayed in various wards throughout the hospital complex over a 13 month period from January 2023 to February 2024. At present, the only representatives of the pQEB1 lineage in GenBank were carried by an Enterobacter hormaechei isolated from a blood sample at the QE in 2016 and a Klebsiella pneumoniae isolated from a urine sample at University Hospitals Coventry and Warwickshire (UHCW) in May 2023. The UHCW patient had been treated at the QE. Long-read whole-genome sequencing was performed on Oxford Nanopore R10.4.1 flow cells, facilitating comparison of complete plasmid sequences. We identified structural variants of pQEB1 and defined the molecular events responsible for them. These have included IS26-mediated inversions and acquisitions of multiple insertion sequences and transposons, including carriers of mercury or arsenic resistance genes. We found that a particular inversion variant of pQEB1 was strongly associated with the QE Liver speciality after appearing in November 2023, but was found in different specialities and wards in January/February 2024. That variant has so far been seen in five different bacterial hosts from six patients, consistent with recent and ongoing inter-host and inter-patient transmission of pQEB1 in this hospital setting.

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

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Emergence and Expansion of a Carbapenem-Resistant Pseudomonas aeruginosa Clone Are Associated with Plasmid-Borne bla KPC-2 and Virulence-Related Genes.

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OmicsDI is part of the ELIXIR infrastructure

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