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Title:   Author  item
                                            Bearson, Bradley

                                                         - *Brad*item
                                            Brunelle, Brian
  Submitted to: International Journal of Antimicrobial Agents
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/17/2015
                                    Publication  Date: 7/18/2015
                                    Publication URL: http://handle.nal.usda.gov/10113/6048954Citation: Bearson, B.L., Brunelle, B.W. 2015. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella. International Journal of Antimicrobial Agents. 46(2):201-204. https://doi.org/10.1016/j.ijantimicag.2015.04.008.DOI: https://doi.org/10.1016/j.ijantimicag.2015.04.008                                                              
                                Interpretive Summary: Antibiotics are important for the treatment of disease due to bacterial pathogens in both humans and animals. Although the use of antibiotics in human and veterinary medicine may reduce illnesses due to bacteria, the exposure of bacteria to antibiotics may cause unintended effects. For example, use of an antibiotic may select for antibiotic resistant pathogens that will not adequately respond to antibiotic therapy. In this study, we studied the effect of an antibiotic class called fluoroquinolones on the foodborne pathogen Salmonella. The fluoroquinolone antibiotics are inhibitory to a wide range of bacteria and are used to treat a variety of bacterial diseases in both humans and animals. Fluoroquinolone exposure of antibiotic-resistant Salmonella isolates activated bacterial viruses that transferred DNA to another Salmonella strain. The transfer of DNA resulted in antibiotic resistance for the recipient Salmonella strain. Therefore, exposure of an antibiotic-resistant Salmonella strain to the fluoroquinolone antibiotic allowed gene transfer of an antibiotic resistance gene to an originally antibiotic-sensitve Salmonella strain. The potential of fluoroquinolones to stimulate bacterial gene transfer should be considered by physicians and veterinarians as an unintended consequence when selecting an antibiotic to use for bacterial disease treatment.
                                Technical Abstract: Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause damage DNA and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate repair of damaged DNA. However, the SOS response may also induce prophage resulting in the production of infectious virions. Salmonella strains typically contain multiple prophage, and certain strains including phage types DT120 and DT104 contain prophage that upon induction are capable of generalized transduction. We exposed strains of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium DT120 and DT104 to fluoroquinolones important for use in human and veterinary disease therapy to determine if 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 the fluoroquinolones ciprofloxacin, enrofloxacin, and danofloxacin; these bacterial cell lysates were able to transfer the plasmid encoding kanamycin resistance to a recipient, kanamycin-susceptible Salmonella strain by generalized transduction. In addition, we demonstrated that exposure of DT120 to ciprofloxacin induced 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 including the transduction of antibiotic resistance. This suggests that fluoroquinolone usage in human and veterinary medicine may have unintended consequences including the induction of phage-mediated gene transfer from MDR Salmonella. The stimulation of gene transfer in bacteria following exposure to fluoroquinolones should be considered an adverse effect, and clinical decisions concerning the selection of an antibiotic for infectious disease therapy should include this potential risk.


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