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Title:   Author  item
                                            Bearson, Bradley

                                                         - *Brad*item
                                            Brunelle, Brian
  Submitted to: ASM Conference
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 3/18/2015
                                    Publication  Date: 5/8/2015
                                    Citation: Bearson, B.L., Brunelle, B.W. 2015. Fluoroquinolone-induced gene transfer in multidrug-resistant Salmonella [abstract]. ASM Conference. 4th ASM Conference on Antimicrobial Resistance in Zoonotic Bacteria and Foodbourne Pathogens. p. 15.Interpretive Summary:
                                Technical Abstract: Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity.  Bacterial exposure to fluoroquinolones can cause DNA damage and induce a bacterial SOS response to stimulate repair of damaged DNA.  Certain prophages (integrated in bacterial chromosomes) may be induced by the SOS response, resulting in the production of infectious virions.  Salmonella strains typically contain multiple prophages within their genome; some isolates including multidrug-resistant (MDR) phage types DT120 and DT104 contain prophage that upon induction are capable of generalized transduction. Generalized transducing phage can randomly package bacterial DNA (chromosome or plasmid) into the phage capsid and transfer the non-phage DNA to a recipient bacterium.  We previously demonstrated that the agricultural antibiotic carbadox can induce phage-mediated, horizontal gene transfer in MDR Salmonella enterica serovar Typhimurium phage types DT120 and DT104 (Bearson et al. Front. Microbiol. 5:52).  In the current study, we exposed strains of MDR S. Typhimurium DT120 and DT104 to fluoroquinolones important for use in human and veterinary disease therapy to determine if prophage(s) could be induced by these antibiotics, and whether prophage induction would facilitate gene transfer.  We used transduction of a native Salmonella plasmid as a model to monitor generalized transduction frequency.  Cultures of MDR S. Typhimurium DT120 and DT104, containing a plasmid encoding kanamycin resistance, lysed after exposure to the fluoroquinolones ciprofloxacin, enrofloxacin, and danofloxacin; these bacterial cell lysates were able to transfer the plasmid conferring kanamycin resistance to a recipient, kanamycin-susceptible Salmonella strain by generalized transduction.  In addition, we demonstrated that exposure of DT120 to ciprofloxacin significantly increased transcription of the recA gene of the bacterial SOS response as well as the abc2 and kil genes encoded in a P22-like generalized transducing prophage.  Our research indicates that fluoroquinolone exposure of MDR Salmonella can facilitate horizontal gene transfer of antibiotic resistance by generalized transduction.  The use of fluoroquinolones 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 concerning antibiotic selection for infectious disease therapy should include this potential risk.


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