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

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      Publication Details (including relevant citation   information):

      Hornsey, Michael, Ellington, Matthew J., Doumith, Michel, Thomas,   Claire P., Gordon, Nicola C., Wareham, David W., Quinn, John,   Lolans, Karen, Livermore, David M., Woodford, Neil Journal of   Antimicrobial Chemotherapy 2010 65  (8 ) 1589 -1593

      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.

      Address (URL): http://jac.oxfordjournals.org/content/65/8/1589.abstract