Campus Units

Veterinary Microbiology and Preventive Medicine, Physics and Astronomy

Document Type

Article

Publication Version

Published Version

Publication Date

9-20-2016

Journal or Book Title

mBio

Volume

7

Issue

5

First Page

e01543-16

DOI

10.1128/mBio.01543-16

Abstract

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.

Comments

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.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

Yao et al.

Language

en

File Format

application/pdf