Key Role of Mfd in the Development of Fluoroquinolone Resistance in Campylobacter jejuni

dc.contributor.author Han, Jing
dc.contributor.author Sahin, Orhan
dc.contributor.author Zhang, Qijing
dc.contributor.author Barton, Yi-Wen
dc.contributor.author Zhang, Qijing
dc.contributor.department Veterinary Microbiology and Preventive Medicine
dc.date 2018-02-17T11:19:11.000
dc.date.accessioned 2020-07-07T05:14:28Z
dc.date.available 2020-07-07T05:14:28Z
dc.date.copyright Tue Jan 01 00:00:00 UTC 2008
dc.date.issued 2008-06-06
dc.description.abstract <p><em>Campylobacter jejuni</em> is a major food-borne pathogen and a common causative agent of human enterocolitis. Fluoroquinolones are a key class of antibiotics prescribed for clinical treatment of enteric infections including campylobacteriosis, but fluoroquinolone-resistant <em>Campylobacter</em>readily emerges under the antibiotic selection pressure. To understand the mechanisms involved in the development of fluoroquinolone-resistant C<em>ampylobacter</em>, we compared the gene expression profiles of <em>C. jejuni</em> in the presence and absence of ciprofloxacin using DNA microarray. Our analysis revealed that multiple genes showed significant changes in expression in the presence of a suprainhibitory concentration of ciprofloxacin. Most importantly, ciprofloxacin induced the expression of <em>mfd</em>, which encodes a transcription-repair coupling factor involved in strand-specific DNA repair. Mutation of the <em>mfd</em> gene resulted in an approximately 100-fold reduction in the rate of spontaneous mutation to ciprofloxacin resistance, while overexpression of <em>mfd</em> elevated the mutation frequency. In addition, loss of<em>mfd</em> in <em>C. jejuni</em> significantly reduced the development of fluoroquinolone-resistant<em>Campylobacter</em> in culture media or chickens treated with fluoroquinolones. These findings indicate that Mfd is important for the development of fluoroquinolone resistance in<em>Campylobacter</em>, reveal a previously unrecognized function of Mfd in promoting mutation frequencies, and identify a potential molecular target for reducing the emergence of fluoroquinolone-resistant <em>Campylobacter</em>.</p>
dc.description.comments <p>This article is from PLoS Pathog 4(6): e1000083. doi:<a href="http://dx.doi.org/10.1371/journal.ppat.1000083" target="_blank">10.1371/journal.ppat.1000083</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vmpm_pubs/129/
dc.identifier.articleid 1130
dc.identifier.contextkey 8049442
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vmpm_pubs/129
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/92231
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vmpm_pubs/129/2008_Han_KeyRole.pdf|||Fri Jan 14 19:32:45 UTC 2022
dc.source.uri 10.1371/journal.ppat.1000083
dc.subject.disciplines Animal Diseases
dc.subject.disciplines Bacterial Infections and Mycoses
dc.subject.disciplines Bacteriology
dc.subject.disciplines Veterinary Infectious Diseases
dc.subject.disciplines Veterinary Microbiology and Immunobiology
dc.subject.disciplines Veterinary Preventive Medicine, Epidemiology, and Public Health
dc.subject.disciplines Veterinary Toxicology and Pharmacology
dc.subject.keywords Campylobacter
dc.subject.keywords Chickens
dc.subject.keywords DNA repair
dc.subject.keywords DNA transcription
dc.subject.keywords Mutation
dc.subject.keywords Birds
dc.subject.keywords Polymerase chain reaction
dc.subject.keywords Antimicrobials
dc.title Key Role of Mfd in the Development of Fluoroquinolone Resistance in Campylobacter jejuni
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 1c6a5dfc-c604-457f-85be-122910db782e
relation.isOrgUnitOfPublication 16f8e472-b1cd-4d8f-b016-09e96dbc4d83
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