Abstract
The emergence of carbapenem-resistant Pseudomonas aeruginosa represents a worldwide problem. To understand the carbapenem-resistance mechanisms and their spreading among P. aeruginosa strains, whole genome sequences were determined of two extensively drug-resistant strains that are endemic in Dutch hospitals. Strain Carb01 63 is of O-antigen serotype O12 and of sequence type ST111, whilst S04 90 is a serotype O11 strain of ST446. Both strains carry a gene for metallo-β-lactamase VIM-2 flanked by two aacA29 genes encoding aminoglycoside acetyltransferases on a class 1 integron. The integron is located on the chromosome in strain Carb01 63 and on a plasmid in strain S04 90. The backbone of the 159-kb plasmid, designated pS04 90, is similar to a previously described plasmid, pND6-2, from Pseudomonas putida. Analysis of the context of the integron showed that it is present in both strains on a ∼30-kb mosaic DNA segment composed of four different transposons that can presumably act together as a novel, active, composite transposon. Apart from the presence of a 1237-bp insertion sequence element in the composite transposon on pS04 90, these transposons show > 99% sequence identity indicating that transposition between plasmid and chromosome could have occurred only very recently. The pS04 90 plasmid could be transferred by conjugation to a susceptible P. aeruginosa strain. A second class 1 integron containing a gene for a CARB-2 β-lactamase flanked by an aacA4′-8 and an aadA2 gene, encoding an aminoglycoside acetyltransferase and adenylyltransferase, respectively, was present only in strain Carb01 63. This integron is located also on a composite transposon that is inserted in an integrative and conjugative element on the chromosome. Additionally, this strain contains a frameshift mutation in the oprD gene encoding a porin involved in the transport of carbapenems across the outer membrane. Together, the results demonstrate that integron-encoded carbapenem and carbapenicillin resistance can easily be disseminated by transposition and conjugation among Pseudomonas aeruginosa strains.
Highlights
MATERIALS AND METHODSPseudomonas aeruginosa is an opportunistic gram-negative pathogen causing acute and chronic infections in hospitalized and immune-compromised patients (Kerr and Snelling, 2009)
To understand the carbapenem-resistance mechanisms and their spreading among P. aeruginosa strains, whole genome sequences were determined of two extensively drug-resistant strains that are endemic in Dutch hospitals
The results demonstrate that integron-encoded carbapenem and carbapenicillin resistance can be disseminated by transposition and conjugation among Pseudomonas aeruginosa strains
Summary
MATERIALS AND METHODSPseudomonas aeruginosa is an opportunistic gram-negative pathogen causing acute and chronic infections in hospitalized and immune-compromised patients (Kerr and Snelling, 2009). P. aeruginosa can rapidly become resistant to antibiotics due to various mechanisms (Oliver et al, 2015), including chromosomal mutations leading to inducible hyper-production of chromosomal AmpC β-lactamase, overexpression of efflux pumps, and/or reduced membrane permeability. Such mutations together are referred to as the mutational resistome (LopézCausapé et al, 2018). The increasing prevalence of metallo-β-lactamases (MBLs), such as VIM or IMP, can be caused by horizontal acquisition of integrons, which are often found to contain genes encoding aminoglycoside resistance. The population structure was termed non-clonal epidemic, with a high recombination frequency between isolates (Kidd et al, 2012)
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