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Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla _VIM-2 and bla _KPC-2 Genes That Spread on Different Genetic Environment in Colombia.

ABSTRACT: Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with an increase in the frequency of infections caused by multidrug resistant (MDR) and extensively drug resistant (XDR) strains, limiting the available therapeutic options. The most troublesome resistance is the acquisition and production of carbapenemases such as Verona integron-encoded metallo-β-lactamases (VIM), the most frequent and widespread, and the Klebsiella pneumoniae carbapenemases (KPC), which has continuously spread in the last decade. Its dissemination is linked to their location on mobile genetic elements (MGEs). In Colombia, VIM and KPC have been increasing in its frequency showing major successful dissemination. In this article, we molecularly characterized and analyzed the genetic context of bla _VIM and bla _KPC in carbapenem-resistant P. aeruginosa (CRPA) isolates from infected and colonized patients in two tertiary-care hospitals, one in Medellín and the other in a municipality close to Medellín, both areas with high carbapenemase endemicity in Colombia (2013-2015). Using whole-genome sequencing (WGS), we identified a remarkable variety of genetic backgrounds in these MDR P. aeruginosa isolates carrying bla _KPC- ₂ and bla _VIM- ₂. There were a diversity of class 1 integron and variations in the gene cassettes associated to bla _VIM- ₂, as well as a possible event of spread of bla _KPC- ₂ mediated by a plasmid that contained part of Tn4401b in one infection case. The dissemination of bla _VIM- ₂ and bla _KPC- ₂ in P. aeruginosa in this area in Colombia has been strongly influenced by successful international clones, carrying these genes and additional determinants of resistance on MGEs, accompanied by gene rearrangement under an antimicrobial selection pressure. These findings emphasize the need to implement control strategies based on rational antibiotic use.

SUBMITTER: Rada AM

PROVIDER: S-EPMC8432936 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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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Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla _VIM-2 and bla _KPC-2 Genes That Spread on Different Genetic Environment in Colombia.

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Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla VIM-2 and bla KPC-2 Genes That Spread on Different Genetic Environment in Colombia.

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OmicsDI is part of the ELIXIR infrastructure

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Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla _VIM-2 and bla _KPC-2 Genes That Spread on Different Genetic Environment in Colombia.