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The Heterodimeric ABC Transporter EfrCD Mediates Multidrug Efflux in Enterococcus faecalis
Lea M Hürlimann1, Valentina Corradi2, Michael Hohl1
1Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Antimicrobial Agents and Chemotherapy
|July 7, 2016
Summary
Seven ABC transporters in Enterococcus faecalis were investigated for drug efflux. EfrCD and EfrEF showed drug efflux activity, while others may have different functions, challenging current annotations of multidrug efflux pumps.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Nosocomial infections caused by Enterococcus faecalis are a growing concern.
- Drug efflux pumps contribute to intrinsic drug resistance but are understudied in E. faecalis.
Purpose of the Study:
- To functionally investigate seven heterodimeric ABC transporters in E. faecalis annotated as drug efflux pumps.
- To determine the role of these transporters in drug resistance and identify novel drug efflux mechanisms.
Main Methods:
- Gene deletion and heterologous expression in Lactococcus lactis.
- Purification of heterodimeric transporters and reconstitution into proteoliposomes.
- Assays for drug efflux activity, substrate binding, and ATP hydrolysis.
Main Results:
- Deletion of ef0789-ef0790 (EfrCD) increased susceptibility to specific drugs.
- EfrAB, EfrCD, and EfrEF mediated efflux of fluorescent substrates and conferred resistance in heterologous expression.
- Four transporters showed no drug efflux activity despite successful purification and reconstitution.
- Functional coupling between ATP hydrolysis and drug binding was observed for EfrAB, EfrCD, and EfrEF.
Conclusions:
- EfrCD and EfrEF function as drug efflux pumps in E. faecalis.
- Many annotated multidrug efflux pumps may not transport drugs and could have other physiological roles.
- This study provides a basis for accurate prediction of drug efflux transporter function.
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