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

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2016-09-20
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Yao, Hong
Shen, Zhangqi
Wang, Yang
Deng, Fengru
Liu, Dejun
Naren, Gaowa
Dai, Lei
Su, Chih-Chia
Wang, Bing
Wang, Shaolin
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Zhang, Qijing
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Physics and Astronomy
Physics and astronomy are basic natural sciences which attempt to describe and provide an understanding of both our world and our universe. Physics serves as the underpinning of many different disciplines including the other natural sciences and technological areas.
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Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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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 Campylobacter, 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 Campylobacter 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 Campylobacter jejuni 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.

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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: 10.1128/mBio.01543-16. Posted with permission.

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Fri Jan 01 00:00:00 UTC 2016
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