Functional effects of intramembranous proline substitutions in the staphylococcal multidrug transporter QacA

Karl A. Hassan, Melanie Galea, Jingqin Wu, Bernadette A. Mitchell, Ronald A. Skurray, Melissa H. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The QacA multidrug transporter is encoded on Staphylococcus aureus multidrug resistance plasmids and confers broad-range antimicrobial resistance to more than 30 monovalent and bivalent lipophilic, cationic compounds from at least 12 different chemical classes. QacA contains 10 proline residues predicted to be within transmembrane regions, several of which are conserved in related export proteins. Proline residues are classically known as helix-breakers and are highly represented within the transmembrane helices of membrane transport proteins, where they can mediate the formation of structures essential for protein stability and transport function. The importance of these 10 intramembranous proline residues for QacA-mediated transport function was determined by examining the functional effect of substituting these residues with glycine, alanine or serine. Several proline-substituted QacA mutants failed to confer high-level resistance to selected QacA substrates. However, no single proline mutation, including those at conserved positions, significantly disrupted QacA protein expression or QacA-mediated resistance to all representative substrates, suggesting that these residues are not essential for the formation of structures requisite to the QacA substrate transport mechanism.

Original languageEnglish
Pages (from-to)76-85
Number of pages10
JournalFEMS Microbiology Letters
Volume263
Issue number1
DOIs
Publication statusPublished - Oct 2006
Externally publishedYes

Keywords

  • Antimicrobial resistance
  • Major facilitator superfamily
  • Multidrug transport
  • Proline mutagenesis
  • QacA
  • Staphylococcus aureus

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