title: Synthesis of metallo-β-lactamase VIM-2 is associated with a fitness reduction in Salmonella enterica Serovar Typhimurium.
abstract: Antibiotic resistance, especially due to β-lactamases, has become one of the main obstacles in the correct treatment of Salmonella infections; furthermore, antibiotic resistance determines a gain of function that may encompass a biological cost, or fitness reduction, to the resistant bacteria. The aim of this work was to determine in vitro if the production of the class B β-lactamase VIM-2 determined a fitness cost for Salmonella enterica serovar Typhimurium. To that end the gene blaVIM-2 was cloned into the virulent strain S. Typhimurium SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid pST12, for inducible and constitutive expression, respectively. Fitness studies were performed by means of motility, growth rate, invasiveness in epithelial cells, and plasmid stability. The expression of blaVIM-2 was accompanied by alterations in micro- and macroscopic morphology and reduced growth rate and motility, as well as diminished invasiveness in epithelial cells. These results suggest that VIM-2 production entails a substantial fitness cost for S. Typhimurium, which in turn may account for the extremely low number of reports of metallo-β-lactamase-producing Salmonella spp.
authors.affiliation: Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Nicolás F
authors.initials: NF
authors.lastname: Cordeiro
authors.affiliation: Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: José A
authors.initials: JA
authors.lastname: Chabalgoity
authors.affiliation: Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Lucía
authors.initials: L
authors.lastname: Yim
authors.affiliation: Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay rvignoli@higiene.edu.uy.
authors.forename: Rafael
authors.identifier: http://orcid.org/0000-0002-2098-9966
authors.initials: R
authors.lastname: Vignoli
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D018938:Caco-2 Cells; D002460:Cell Line; D003001:Cloning, Molecular; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004847:Epithelial Cells / Q000382:microbiology; D056084:Genetic Fitness / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C425108:beta-lactamase bla(vim-2); D001618:beta-Lactamases; C063912:carbapenemase