title: Chromosome-mediated OXA-48 carbapenemase in highly virulent Escherichia coli.
abstract: OBJECTIVE
  Bacteria multiresistant to antibiotics are widely supposed to be weakly virulent. However, the virulence traits of carbapenem-resistant Enterobacteriaceae have not been investigated. In this work, we investigated the virulence and resistance mechanism of an extraintestinal pathogenic Escherichia coli (ExPEC) strain (LEB15) that exhibited decreased susceptibility to carbapenems.
  
  
  METHODS
  The MICs were determined by a microdilution method. The β-lactamase-encoding gene was identified by PCR and sequencing, and the genetic environment was analysed by PFGE and PCR mapping. The genetic background was investigated by multilocus sequence typing (MLST). Virulence-factor-encoding genes and pathogenic islands (PAIs) were detected by multiplex PCR. Virulence was assessed in a mouse sepsis model.
  
  
  RESULTS
  Strain LEB15 produced a chromosomal OXA-48 carbapenemase. The complete bla(OXA-48)-encoding Tn1999.2 transposon was inserted in the LEB15 chromosome. The strain belonged to an MLST cluster of emerging ExPEC strains (ST-127/ST-22). It had a high pathogenic score and eight PAIs (I536, II536, III536, IV536, VI536, I(CFT073), II(CFT073) and II(J96)) and induced an unusually high lethality in the mouse sepsis model.
  
  
  CONCLUSIONS
  Strain LEB15 combines both an atypical broad accumulation of virulence factors, which confers a strong killer phenotype, and a decrease in susceptibility to carbapenems following the chromosomal acquisition of bla(OXA-48). This association of virulence and carbapenemase in E. coli strains might pose major problems in the future for E. coli infection management.
authors: Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.
authors: Racha
authors: R
authors: Beyrouthy
authors: Frédéric
authors: F
authors: Robin
authors: Antony
authors: A
authors: Cougnoux
authors: Guillaume
authors: G
authors: Dalmasso
authors: Arlette
authors: A
authors: Darfeuille-Michaud
authors: Hassan
authors: H
authors: Mallat
authors: Fouad
authors: F
authors: Dabboussi
authors: Monzer
authors: M
authors: Hamzé
authors: Richard
authors: R
authors: Bonnet
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002876:Chromosomes, Bacterial; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D037521:Virulence Factors; D001618:beta-Lactamases; C063912:carbapenemase
keywords: E. coli; pathogenic islands; virulence