title: Phenotypic changes in a laboratory-derived ertapenem-resistant Escherichia coli strain.
abstract: The aim of this study was to identify phenotypic changes in a laboratory-derived strain of ertapenem-resistant Escherichia coli (Ec-ERT) when compared to its susceptible parent strain (Ec-WT). In both strains, we assessed both the effects of ertapenem via time-kill curves and the occurrence of cross resistance with other beta-lactams. The strains were compared based on growth pattern, biochemical-physiological profile and changes in the subproteome using 2D-DIGE followed by MALDI-TOF/TOF MS. To assess virulence, we employed a murine model of intraperitoneal infection in which we investigated the invasiveness of both strains. Growth persistence of the laboratory-derived resistant strain was observed via the time-kill curve assay, but cross resistance was not observed for other beta-lactams. We also observed a slower growth rate and changes in the biochemical and physiological characteristics of the drug-resistant bacteria. In the resistant strain, a total of 51 protein spots were increased in abundance relative to the wild-type strain, including an outer membrane protein A, which is related to bacterial virulence. The mouse infection assay showed a higher invasiveness of the Ec-ERT strain in relation to the Ec-WT strain. In conclusion, the alterations driven by ertapenem in E. coli reinforce the idea that antimicrobial agents may interfere in several aspects of bacterial cell biology, with possible implications for host-bacteria interactions.
authors: Departamento de Patologia, Centro de Cièncias da Saúde, Universidade Federal do Espirito Santo, Vitória, ES, Brazil.
authors: K V
authors: KV
authors: Santos
authors: M A R
authors: MA
authors: Carvalho
authors: W A
authors: WA
authors: Martins
authors: H M
authors: HM
authors: Andrade
authors: L C
authors: LC
authors: Veloso
authors: S C
authors: SC
authors: Coutinho
authors: J L
authors: JL
authors: Bahia
authors: J P L
authors: JP
authors: Andrade
authors: A C M
authors: AC
authors: Apolonio
authors: C G
authors: CG
authors: Diniz
authors: J R
authors: JR
authors: Nicoli
authors: L M
authors: LM
authors: Farias
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D057825:Two-Dimensional Difference Gel Electrophoresis; D014774:Virulence; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D047090:beta-Lactams; C078167:OMPA outer membrane proteins; D000077727:Ertapenem