title: Intraclonal Genome Stability of the Metallo-β-lactamase SPM-1-producingPseudomonas aeruginosaST277, an Endemic Clone Disseminated in Brazilian Hospitals.
abstract: Carbapenems represent the mainstay therapy for the treatment of seriousP. aeruginosainfections. 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 inP. aeruginosaisolated from Brazilian medical centers. Interestingly, a single SPM-1-producingP. aeruginosaclone 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-producingP. aeruginosaST277 isolates. The core genome contains 5899 coding genes relative to the reference strainP. 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 theblaSPM-1gene 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-producingP. aeruginosaST277 clone. A comparison of the SPM-1-producingP. aeruginosaST277 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.
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Ana P B
authors.initials: AP
authors.lastname: Nascimento
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Mauro F
authors.initials: MF
authors.lastname: Ortiz
authors.affiliation: Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Willames M B S
authors.initials: WM
authors.lastname: Martins
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Morais
authors.affiliation: Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Lorena C C
authors.initials: LC
authors.lastname: Fehlberg
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Luiz G P
authors.initials: LG
authors.lastname: Almeida
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Luciane P
authors.initials: LP
authors.lastname: Ciapina
authors.affiliation: Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Gales
authors.affiliation: Laboratório de Bioinformática, Laboratório Nacional de Computação Científica Petrópolis, Brazil.
authors.forename: Ana T R
authors.initials: AT
authors.lastname: Vasconcelos
keywords: Gram-negative bacilli; antimicrobial resistance; carbapenemase; comparative genomics; drug resistance; pathogenic bacteria