Microbial drug efflux proteins of the major facilitator superfamily

Massoud Saidijam, Giulia Benedetti, Qinghu Ren, Zhiqiang Xu, Christopher J. Hoyle, Sarah L. Palmer, Alison Ward, Kim E. Bettaney, Gerda Szakonyi, Johan Meuller, Scott Morrison, Martin K. Pos, Patrick Butaye, Karl Walravens, Kate Langton, Richard B. Herbert, Ronald A. Skurray, Ian T. Paulsen, John O'Reilly, Nicolas G. Rutherford & 3 others Melissa H. Brown, Roslyn M. Bill, Peter J F Henderson*

*Corresponding author for this work

Research output: Contribution to journalReview article

62 Citations (Scopus)

Abstract

Drug efflux proteins are widespread amongst microorganisms, including pathogens. They can contribute to both natural insensitivity to antibiotics and to emerging antibiotic resistance and so are potential targets for the development of new antibacterial drugs. The design of such drugs would be greatly facilitated by knowledge of the structures of these transport proteins, which are poorly understood, because of the difficulties of obtaining crystals of quality. We describe a structural genomics approach for the amplified expression, purification and characterisation of prokaryotic drug efflux proteins of the 'Major Facilitator Superfamily' (MFS) of transport proteins from Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides and Streptomyces coelicolor. The H. pylori putative drug resistance protein, HP1092, and the S. aureus QacA proteins are used as detailed examples. This strategy is an important step towards reproducible production of transport proteins for the screening of drug binding and for optimisation of crystallisation conditions to enable subsequent structure determination.

Original languageEnglish
Pages (from-to)793-811
Number of pages19
JournalCurrent Drug Targets
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Fingerprint Dive into the research topics of 'Microbial drug efflux proteins of the major facilitator superfamily'. Together they form a unique fingerprint.

Cite this