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

Michael Hornsey*, Matthew J. Ellington, Michel Doumith, Claire P. Thomas, Nicola C. Gordon, David W. Wareham, John Quinn, Karen Lolans, David M. Livermore, Neil Woodford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Citations (Scopus)


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.

Original languageEnglish
Article numberdkq218
Pages (from-to)1589-1593
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Issue number8
Publication statusPublished - 16 Jun 2010

Bibliographical note

Funding Information:
This work was supported by an educational grant from Wyeth, now taken over by Pfizer.


  • Glycylcyclines
  • OXA-23 clone 1
  • South-East clone


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