Efflux pumps may play a role in tigecycline resistance in Burkholderia species

Rajendran, Ranjith; Quinn, Ryan F.; Murray, Colin; McCulloch, Elaine; Williams, Craig; Ramage, Gordon

doi:10.1016/j.ijantimicag.2010.03.009

« Previous Next »International Journal of Antimicrobial Agents
Volume 36, Issue 2 , Pages 151-154, August 2010

Efflux pumps may play a role in tigecycline resistance in Burkholderia species

Ranjith Rajendran
- Section of Infection and Immunity, Glasgow Dental School, Faculty of Medicine, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK
Ryan F. Quinn
- Section of Infection and Immunity, Glasgow Dental School, Faculty of Medicine, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK
Colin Murray
- Section of Infection and Immunity, Glasgow Dental School, Faculty of Medicine, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK
Elaine McCulloch
- Department of Microbiology, Royal Hospital for Sick Children, Glasgow, UK
Craig Williams
- Department of Microbiology, Royal Hospital for Sick Children, Glasgow, UK
Gordon Ramage
- Section of Infection and Immunity, Glasgow Dental School, Faculty of Medicine, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK
- Corresponding author. Tel.: +44 141 211 9752; fax: +44 141 353 1593.

Received 22 February 2010; accepted 8 March 2010. published online 20 April 2010.

Abstract

The purpose of this study was to investigate the role of multidrug resistance efflux pumps in relation to decreased susceptibility to tigecycline in clinical isolates of Burkholderia cepacia complex (BCC). The role of efflux pumps was analysed using the efflux pump inhibitor (EPI) MC-207,110. Minimum inhibitory concentrations (MICs) were determined for each strain against tigecycline alone and in the presence of 64mg/L MC-207,110. The effect of efflux pump inhibition on the susceptibility of BCC isolates to tigecycline was assessed by a checkerboard titration assay. Ala-Nap uptake assay was performed to determine efflux pump activity in different strains. The checkerboard titration assay showed that the MIC decreased with increasing concentrations of EPI. MICs for tigecycline in the clinical isolates ranged between 8mg/L and 32mg/L, whereas in the presence of MC-207,110, MICs decreased significantly (range <0.125–1.0mg/L; 16 to >256 times reduction). Efflux pump activity was shown to be greatest in strains with the highest MIC and vice versa. In conclusion, BCC possess efflux pumps that influence their resistance to tigecycline. Use of an inhibitor of these pumps restored sensitivity to the antibiotic. Therefore, a combination of tigecycline and EPI to augment its efficacy may present an attractive therapeutic option.