title: Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella.
abstract: Fluoroquinolones are broad-spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause DNA damage and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate DNA repair. However, the SOS response may also induce prophage with production of infectious virions. Salmonella strains typically contain multiple prophages, and certain strains including phage types DT120 and DT104 contain prophage that upon induction are capable of generalised transduction. In this study, strains of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium DT120 and DT104 were exposed to fluoroquinolones important for use in human and veterinary disease therapy to determine whether prophage(s) are induced that could facilitate phage-mediated gene transfer. Cultures of MDR S. Typhimurium DT120 and DT104 containing a kanamycin resistance plasmid were lysed after exposure to fluoroquinolones (ciprofloxacin, enrofloxacin and danofloxacin). Bacterial cell lysates were able to transfer the plasmid to a recipient kanamycin-susceptible Salmonella strain by generalised transduction. In addition, exposure of DT120 to ciprofloxacin induced the recA gene of the bacterial SOS response and genes encoded in a P22-like generalised transducing prophage. This research indicates that fluoroquinolone exposure of MDR Salmonella can facilitate horizontal gene transfer, suggesting that fluoroquinolone usage in human and veterinary medicine may have unintended consequences, including the induction of phage-mediated gene transfer from MDR Salmonella. Stimulation of gene transfer following bacterial exposure to fluoroquinolones should be considered an adverse effect, and clinical decisions regarding antibiotic selection for infectious disease therapy should include this potential risk.
authors.affiliation: Agroecosystems Management Research Unit, National Laboratory for Agriculture and the Environment, ARS, USDA, 2110 University Drive, NSRIC-2103, Ames, IA, 50011, USA. Electronic address: brad.bearson@ars.usda.gov.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Bearson
authors.affiliation: Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, ARS, USDA, 1920 Dayton Ave., Ames, IA, 50010, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Brunelle
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000009:adverse effects / Q000378:metabolism*; D022761:Gene Transfer, Horizontal / Q000187:drug effects*; D039002:Prophages / Q000235:genetics; D012483:Salmonella Phages / Q000235:genetics*; D012486:Salmonella typhimurium / Q000187:drug effects*; D014161:Transduction, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Bacteriophage; Fluoroquinolone; Gene transfer; Prophage; Salmonella; Transduction