AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii

Hornsey, Michael, Ellington, Matthew J., Doumith, Michel, Thomas, Claire P., Gordon, Nicola C., Wareham, David W., Quinn, John, Lolans, Karen, Livermore, David M. and Woodford, Neil (2010) AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy, 65 (8). pp. 1589-1593. ISSN 0305-7453

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Abstract

Objectives Tigecycline non-susceptibility in individual Acinetobacter baumannii isolates has been associated with up-regulation of the resistance–nodulation–division (RND)-type efflux system, AdeABC. We sought to relate variation in the expression of this system to differences in modal tigecycline MIC among prevalent A. baumannii clones. The role of AdeABC in the emergence of tigecycline resistance during therapy was also investigated for two representatives of the prevalent UK lineage, OXA-23 clone 1. Methods Clonal type was defined by PFGE and expression of adeABC by real-time RT–PCR. Laboratory mutants were selected in vitro by exposing a susceptible clinical isolate to increasing tigecycline concentrations. The adeB gene was inactivated by the directed integration of a suicide plasmid containing an internal fragment of the target gene. Results Higher modal tigecycline MICs for particular clones correlated with elevated expression of adeABC. Expression of this operon was also increased in the two post-therapy, tigecycline-resistant clinical isolates and in a laboratory mutant as compared with their pre-exposure, tigecycline-susceptible counterparts. Interruption of adeB in a tigecycline-resistant clinical isolate restored full susceptibility to tigecycline. Conclusions Differences in expression of adeABC contribute to both inter- and intra-clone variation in tigecycline MICs. Tigecycline resistance can arise during therapy, mediated by up-regulation of AdeABC.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Rhiannon Harvey
Date Deposited: 05 Jul 2011 10:46
Last Modified: 21 Apr 2020 16:59
URI: https://ueaeprints.uea.ac.uk/id/eprint/33341
DOI: 10.1093/jac/dkq218

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