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

被引:128
作者
Hornsey, Michael [1 ]
Ellington, Matthew J. [1 ]
Doumith, Michel [1 ]
Thomas, Claire P. [2 ]
Gordon, Nicola C. [3 ]
Wareham, David W. [3 ]
Quinn, John [4 ]
Lolans, Karen [4 ]
Livermore, David M. [1 ]
Woodford, Neil [1 ]
机构
[1] Hlth Protect Agcy Ctr Infect, Antibiot Resistance Monitoring & Reference Lab, London NW9 5EQ, England
[2] Hammersmith Hosp, Imperial Coll Healthcare NHS Trust, London W12 0HS, England
[3] Barts & London NHS Trust, Div Infect, London E1 2ES, England
[4] Chicago Infect Dis Res Inst, Chicago, IL 60614 USA
关键词
glycylcyclines; OXA-23; clone; 1; South-East clone; SOUTHEAST ENGLAND; RESISTANCE; EXPRESSION; PUMP;
D O I
10.1093/jac/dkq218
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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. 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. 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. 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.
引用
收藏
页码:1589 / 1593
页数:5
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