Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics

dc.contributor.author Yao, Hong
dc.contributor.author Shen, Zhangqi
dc.contributor.author Wang, Yang
dc.contributor.author Deng, Fengru
dc.contributor.author Liu, Dejun
dc.contributor.author Naren, Gaowa
dc.contributor.author Dai, Lei
dc.contributor.author Su, Chih-Chia
dc.contributor.author Wang, Bing
dc.contributor.author Wang, Shaolin
dc.contributor.author Wu, Congming
dc.contributor.author Yu, Edward
dc.contributor.author Zhang, Qijing
dc.contributor.author Shen, Jianzhong
dc.contributor.department Physics and Astronomy
dc.contributor.department Veterinary Microbiology and Preventive Medicine
dc.date 2018-02-18T22:48:41.000
dc.date.accessioned 2020-07-07T05:14:31Z
dc.date.available 2020-07-07T05:14:31Z
dc.date.copyright Fri Jan 01 00:00:00 UTC 2016
dc.date.issued 2016-09-20
dc.description.abstract <p>Bacterial antibiotic efflux pumps are key players in antibiotic resistance. Although their role in conferring multidrug resistance is well documented, the emergence of “super” efflux pump variants that enhance bacterial resistance to multiple drugs has not been reported. Here, we describe the emergence of a resistance-enhancing variant (named RE-CmeABC) of the predominant efflux pump CmeABC in <em>Campylobacter</em>, a major zoonotic pathogen whose resistance to antibiotics is considered a serious antibiotic resistance threat in the United States. Compared to the previously characterized CmeABC transporters, RE-CmeABC is much more potent in conferring <em>Campylobacter</em> resistance to antibiotics, which was shown by increased MICs and reduced intracellular accumulation of antibiotics. Structural modeling suggests that sequence variations in the drug-binding pocket of CmeB possibly contribute to the enhanced efflux function. Additionally, RE-CmeABC expands the mutant selection window of ciprofloxacin, enhances the emergence of antibiotic-resistant mutants, and confers exceedingly high-level resistance to fluoroquinolones, an important class of antibiotics for clinical therapy of campylobacteriosis. Furthermore, RE-CmeABC is horizontally transferable, shifts antibiotic MIC distribution among clinical isolates, and is increasingly prevalent in <em>Campylobacter jejuni</em> isolates, suggesting that it confers a fitness advantage under antimicrobial selection. These findings reveal a new mechanism for enhanced multidrug resistance and an effective strategy utilized by bacteria for adaptation to selection from multiple antibiotics.</p>
dc.description.comments <p>This article is published as Yao, Hong, Zhangqi Shen, Yang Wang, Fengru Deng, Dejun Liu, Gaowa Naren, Lei Dai et al. "Emergence of a potent multidrug efflux pump variant that enhances Campylobacter resistance to multiple antibiotics." mBio 7, no. 5 (2016): e01543-16. doi: <a href="http://dx.doi.org/10.1128/mBio.01543-16%20" target="_blank" title="Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics ">10.1128/mBio.01543-16</a>. Posted with permission.</p>
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dc.identifier archive/lib.dr.iastate.edu/vmpm_pubs/137/
dc.identifier.articleid 1136
dc.identifier.contextkey 10742097
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vmpm_pubs/137
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/92240
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vmpm_pubs/137/2016_Zhang_EmergencePotent.pdf|||Fri Jan 14 19:59:01 UTC 2022
dc.source.uri 10.1128/mBio.01543-16
dc.subject.disciplines Biological and Chemical Physics
dc.subject.disciplines Veterinary Infectious Diseases
dc.subject.disciplines Veterinary Medicine
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.subject.disciplines Veterinary Toxicology and Pharmacology
dc.title Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 1c6a5dfc-c604-457f-85be-122910db782e
relation.isOrgUnitOfPublication 4a05cd4d-8749-4cff-96b1-32eca381d930
relation.isOrgUnitOfPublication 16f8e472-b1cd-4d8f-b016-09e96dbc4d83
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