J. Mol. Micro. Biotechnol. 3: 163-170
Staphylococcal Multidrug Efflux Protein QacA
Melissa H. Brown and Ronald A. Skurray
The QacA multidrug exporter from Staphylococcus
aureus mediates resistance to a wide array of
monovalent or divalent cationic, lipophilic, antimicrobial compounds. QacA provides resistance to these various
compounds via a proton motive force-dependent antiport mechanism that conforms to classical Michaelis-Menten
kinetics. Fluorescent transport analyses have demonstrated that this QacA:substrate interaction occurs with high
affinity and competition studies have shown that QacA-mediated ethidium export is competitively inhibited by
other monovalent cations, and non-competitively inhibited by divalent cations, suggesting that monovalent and
divalent cations bind at distinct sites on the QacA protein. The closely related export protein QacB, mediates
lower levels of resistance to divalent cations, and lacks a high affinity-binding site for divalent cations. The
cell membrane has been identified as the origin of QacA-mediated efflux; substrates are bound and expelled
from within this hydrophobic environment.
Regulation of qacA expression is achieved via the
trans-acting repressor protein, QacR. QacR belongs
to the TetR family of transcriptional repressor proteins, which all possess a helix-turn-helix DNA-binding
domain at their N-terminal ends, and have highly divergent C-termini postulated to be involved in the binding of
inducing compounds. QacR specifically binds to an inverted repeat, IR1, which has been identified as the
qacA operator region, and overlaps the identified promoter sequence for
qacA. QacR, like the multidrug export protein
whose expression it regulates, has been shown to interact directly with a number of structurally-dissimilar compounds.
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