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, G. 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

Research output: Contribution to journalArticle

59 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

Fingerprint

Carrier Proteins
Helicobacter pylori
Pharmaceutical Preparations
Brucella melitensis
Streptomyces coelicolor
Neisseria
Preclinical Drug Evaluations
Proteins
Campylobacter jejuni
Enterococcus faecalis
Drug Design
Protein S
Microbial Drug Resistance
Genomics
Crystallization
Bacillus subtilis
Meningitis
Drug Resistance
Staphylococcus aureus
Escherichia coli

Keywords

  • Antibiotic resistance
  • Drug resistance
  • Gene expression
  • Membrane protein
  • Membrane transport
  • Multidrug resistance
  • Protein production
  • Transport protein

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Saidijam, M., Benedetti, G., Ren, Q., Xu, Z., Hoyle, C. J., Palmer, S. L., ... Henderson, P. J. F. (2006). Microbial drug efflux proteins of the major facilitator superfamily. Current Drug Targets, 7(7), 793-811. https://doi.org/10.2174/138945006777709575

Microbial drug efflux proteins of the major facilitator superfamily. / Saidijam, Massoud; Benedetti, Giulia; Ren, Qinghu; Xu, Zhiqiang; Hoyle, Christopher J.; Palmer, Sarah L.; Ward, Alison; Bettaney, Kim E.; Szakonyi, G.; Meuller, Johan; Morrison, Scott; Pos, Martin K.; Butaye, Patrick; Walravens, Karl; Langton, Kate; Herbert, Richard B.; Skurray, Ronald A.; Paulsen, Ian T.; O'Reilly, John; Rutherford, Nicolas G.; Brown, Melissa H.; Bill, Roslyn M.; Henderson, Peter J F.

In: Current Drug Targets, Vol. 7, No. 7, 07.2006, p. 793-811.

Research output: Contribution to journalArticle

Saidijam, M, Benedetti, G, Ren, Q, Xu, Z, Hoyle, CJ, Palmer, SL, Ward, A, Bettaney, KE, Szakonyi, G, Meuller, J, Morrison, S, Pos, MK, Butaye, P, Walravens, K, Langton, K, Herbert, RB, Skurray, RA, Paulsen, IT, O'Reilly, J, Rutherford, NG, Brown, MH, Bill, RM & Henderson, PJF 2006, 'Microbial drug efflux proteins of the major facilitator superfamily', Current Drug Targets, vol. 7, no. 7, pp. 793-811. https://doi.org/10.2174/138945006777709575
Saidijam M, Benedetti G, Ren Q, Xu Z, Hoyle CJ, Palmer SL et al. Microbial drug efflux proteins of the major facilitator superfamily. Current Drug Targets. 2006 Jul;7(7):793-811. https://doi.org/10.2174/138945006777709575
Saidijam, Massoud ; Benedetti, Giulia ; Ren, Qinghu ; Xu, Zhiqiang ; Hoyle, Christopher J. ; Palmer, Sarah L. ; Ward, Alison ; Bettaney, Kim E. ; Szakonyi, G. ; Meuller, Johan ; Morrison, Scott ; Pos, Martin K. ; Butaye, Patrick ; Walravens, Karl ; Langton, Kate ; Herbert, Richard B. ; Skurray, Ronald A. ; Paulsen, Ian T. ; O'Reilly, John ; Rutherford, Nicolas G. ; Brown, Melissa H. ; Bill, Roslyn M. ; Henderson, Peter J F. / Microbial drug efflux proteins of the major facilitator superfamily. In: Current Drug Targets. 2006 ; Vol. 7, No. 7. pp. 793-811.
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