1. Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii.
- Author
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Sun JR, Jeng WY, Perng CL, Yang YS, Soo PC, Chiang YS, and Chiueh TS
- Subjects
- DNA Shuffling, Gene Knockout Techniques, Genetic Complementation Test, Minocycline pharmacology, Mutagenesis, Site-Directed, Tigecycline, Acinetobacter baumannii drug effects, Acinetobacter baumannii genetics, Amino Acid Substitution, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Membrane Transport Proteins genetics, Minocycline analogs & derivatives
- Abstract
Objectives: Amino acid substitutions within the AdeRS two-component system are believed to result in overexpression of the AdeABC efflux pump and extensive resistance to antibiotics in clinical Acinetobacter baumannii isolates. However, the exact amino acid substitutions in AdeRS that cause overexpression of the AdeABC efflux pump remain unclear. We elucidated the role of amino acid substitutions in AdeRS by a complementation assay in an adeRS knockout strain of A. baumannii., Methods: Five types of adeRS operon from tigecycline-resistant XDR A. baumannii (XDRAB) were cloned and introduced into the adeRS knockout strain to reverse its tigecycline susceptibility., Results: Through shuffling gene segments among those five adeRS operons and performing site-directed mutagenesis, we found that the specific amino acid substitution Gly186Val in AdeS is crucial for reducing tigecycline susceptibility of A. baumannii., Conclusions: Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
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