GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:24634217

From GONUTS
Jump to: navigation, search
Citation

Li, W, Sharma, M and Kaur, P' (2014) The DrrAB system of Streptomyces peucetius is a Multi-Drug Transporter of Broad Substrate Specificity. J. Biol. Chem. '

Abstract

The soil bacterium Streptomyces peucetius produces two widely used anticancer antibiotics doxorubicin and daunorubicin. Present within the biosynthesis gene cluster in S. peucetius is the drrAB operon which codes for a dedicated ABC-type transporter for the export of these two closely related antibiotics. Because of its dedicated nature, the DrrAB system is believed to belong to the category of single-drug transporters. However, whether it also contains specificity for other known substrates of multidrug transporters has never been tested. In this study, we demonstrate under both in vivo and in vitro conditions that the DrrAB system can transport not only doxorubicin but is also able to export two most commonly studied MDR substrates, Hoechst 33342 and ethidium bromide. Moreover, we demonstrate that many other substrates (including verapamil, vinblastine, and rifampicin) of the well-studied multi-drug transporters inhibit DrrAB-mediated Dox transport with high efficiency, indicating that they are also substrates of the DrrAB pump. Kinetic studies show that inhibition of doxorubicin transport by Hoechst 33342 and rifampicin occurs by a competitive mechanism whereas verapamil inhibits transport by a non-competitive mechanism, thus suggesting the possibility of more than one drug binding site in the DrrAB system. This is the first in-depth study of a drug resistance system from a producer organism, and it shows that a dedicated efflux system like DrrAB contains specificity for multiple drugs. The significance of these findings in evolution of poly-specificity in drug resistance systems is discussed.

Links

PubMed Online version:10.1074/jbc.M113.536136

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

STRPE:P72496

GO:0006855: drug transmembrane transport

ECO:0000314:

P

Figure 1 and 3 show how the DrrAB system is involved in multi-drug transport and the kinetics of its functionality.

complete
CACAO 10032

See also

References

See Help:References for how to manage references in GONUTS.