Abstract
Carbapenems represent the mainstay therapy for the treatment of serious P. aeruginosa infections. However, the emergence of carbapenem resistance has jeopardized the clinical use of this important class of compounds. The production of SPM-1 metallo-β-lactamase has been the most common mechanism of carbapenem resistance identified in P. aeruginosa isolated from Brazilian medical centers. Interestingly, a single SPM-1-producing P. aeruginosa clone belonging to the ST277 has been widely spread within the Brazilian territory. In the current study, we performed a next-generation sequencing of six SPM-1-producing P. aeruginosa ST277 isolates. The core genome contains 5899 coding genes relative to the reference strain P. aeruginosa PAO1. A total of 26 genomic islands were detected in these isolates. We identified remarkable elements inside these genomic islands, such as copies of the blaSPM−1 gene conferring resistance to carbapenems and a type I-C CRISPR-Cas system, which is involved in protection of the chromosome against foreign DNA. In addition, we identified single nucleotide polymorphisms causing amino acid changes in antimicrobial resistance and virulence-related genes. Together, these factors could contribute to the marked resistance and persistence of the SPM-1-producing P. aeruginosa ST277 clone. A comparison of the SPM-1-producing P. aeruginosa ST277 genomes showed that their core genome has a high level nucleotide similarity and synteny conservation. The variability observed was mainly due to acquisition of genomic islands carrying several antibiotic resistance genes.
Highlights
Pseudomonas aeruginosa is a ubiquitous microorganism present in many diverse ecological niches, including water, soil, plants, animals, and humans
In Brazil, P. aeruginosa is an important pathogen in the nosocomial environment
This study was undertaken to determine the possible presence of genetic factors associated with the resistance and persistence of this clone within Brazilian institutions In addition, we aimed to compare the genome of the SPM-1-producing P. aeruginosa isolates collected from a single intensive care unit over a 9-year period to evaluate whether this clone had suffered any temporal changes compared with the index isolate.This is the first study to date to comprehensively evaluate and compare the complete genome of the SPM-1-producing P. aeruginosa ST277 isolates, as the genome of few SPM-1-producing P. aeruginosa strains have only been partially analyzed (Boyle et al, 2012; Silveira et al, 2014; van Belkum et al, 2015)
Summary
Pseudomonas aeruginosa is a ubiquitous microorganism present in many diverse ecological niches, including water, soil, plants, animals, and humans. Among P. aeruginosa, hyperproduction of AmpC and/or metallo-β-lactamases coupled with alteration in the outer membrane permeability represent the main mechanism of carbapenem resistance (Lister et al, 2009; Papp-Wallace et al, 2011). According to the latest report of the Brazilian Health Surveillance Agency, P. aeruginosa ranked as the fifth most common pathogen causing catheter-related bloodstream infections in adult patients hospitalized at Brazilian intensive care units. Among the 2480 P. aeruginosa reported, nearly 42% were resistant to carbapenems. The production of SPM-1, São Paulo metallo-β-lactamase, has been the most common mechanism of carbapenem resistance identified in P. aeruginosa isolated from Brazilian medical centers (Toleman et al, 2002; Scheffer et al, 2010; Rossi, 2011). Previous studies have shown the presence of a SPM-1-producing P. aeruginosa clone belonging to the ST277, clone SP, widely spread within the Brazilian territory (Gales et al, 2003; Scheffer et al, 2010; Silva et al, 2011; Silveira et al, 2014)
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