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Gene Review

qacA  -  efflux protein QacA

Staphylococcus aureus

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Disease relevance of qacA


High impact information on qacA

  • The Staphylococcus aureus multidrug binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by structurally diverse cationic lipophilic drugs [5].
  • Primer extension analysis was performed to map the transcription start points of the qacA and divergently transcribed qacR mRNAs [6].
  • An inverted repeat overlapping the qacA transcription start site was shown to be the operator sequence for control of qacA gene expression [6].
  • Resistance to intercalating dyes (ethidium, acriflavine) and other organic cations, such as quaternary ammonium-type antiseptic compounds, mediated by the Staphylococcus aureus plasmid pSK1 is specified by an energy-dependent export mechanism encoded by the qacA gene [1].
  • The putative polypeptide specified by qacA has properties typical of a cytoplasmic membrane protein, and is indicated to be a member of a transport protein family that includes proteins responsible for export-mediated resistance to tetracycline and methylenomycin, and uptake of sugars and quinate [1].

Chemical compound and disease context of qacA


Biological context of qacA

  • From nucleotide sequence analysis, qacA is predicted to encode a protein of Mr 55017 containing 514 amino acids [1].
  • The gene is likely to initiate with a CUG codon, and a 36 bp palindrome immediately preceding qacA, along with an upstream reading frame with homology to the TetR repressors, may be components of a regulatory circuit [1].
  • In conclusion, among these families of efflux pumps, only the multidrug transporter encoded by qacA conferred a tPMP-1r phenotype [9].
  • Of note, the qacA-bearing strain exhibited greater membrane fluidity than that of the parental, qacB-, or qacC-bearing strain [9].
  • The current study evaluated whether (i) transporters encoded by the qacB and qacC multidrug resistance genes also confer tPMP-1r and (ii) tPMP-1r mediated by qacA is dependent on efflux pump activity [9].

Associations of qacA with chemical compounds

  • In synergy assays, exposure of the qacA-bearing strain to tPMP-1 did not affect the susceptibility of Et (ruling out Et-tPMP-1 cotransport) [9].
  • In the three other BC and penicillin-resistant strains, the qacA/B and blaZ genes were located on separate plasmids [10].
  • Our results indicated that four or more antiseptic-resistance genes exist in methicillin-resistant S. aureus and that antiseptic-resistant methicillin-resistant S. aureus strains without qacA and smr are widely spread in Japan [11].
  • Efflux, another important resistance mechanism, is associated with the qacA/B gene system in staphylococci that confers low-level resistance to cationic agents including chlorhexidine salts and quaternary ammonium compounds [12].
  • Resistance to ampicillin, penicillin G and dyes was prevalent in strains harbouring the qacA or qacB genes, features also common among clinical staphylococci containing qacA/qacB [13].

Other interactions of qacA

  • Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity [9].
  • The qacA/B and blaZ probes hybridized to the same plasmid in 19 (24%) staphylococcal strains [3].
  • The plasmids harboring both qacA/B and blaZ genes varied from approximately 20 to 40 kb [3].
  • Twenty-four isolates hosting one of the genes qacA/qacB, smr, qacG or qacH, were subjected to species identification [13].

Analytical, diagnostic and therapeutic context of qacA


  1. Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus: common ancestry with tetracycline- and sugar-transport proteins. Rouch, D.A., Cram, D.S., DiBerardino, D., Littlejohn, T.G., Skurray, R.A. Mol. Microbiol. (1990) [Pubmed]
  2. Organization of the antiseptic resistance gene qacA and Tn552-related beta-lactamase genes in multidrug- resistant Staphylococcus haemolyticus strains of animal and human origins. Anthonisen, I.L., Sunde, M., Steinum, T.M., Sidhu, M.S., Sørum, H. Antimicrob. Agents Chemother. (2002) [Pubmed]
  3. Frequency of disinfectant resistance genes and genetic linkage with beta-lactamase transposon Tn552 among clinical staphylococci. Sidhu, M.S., Heir, E., Leegaard, T., Wiger, K., Holck, A. Antimicrob. Agents Chemother. (2002) [Pubmed]
  4. Antimicrobial agent of susceptibilities and antiseptic resistance gene distribution among methicillin-resistant Staphylococcus aureus isolates from patients with impetigo and staphylococcal scalded skin syndrome. Noguchi, N., Nakaminami, H., Nishijima, S., Kurokawa, I., So, H., Sasatsu, M. J. Clin. Microbiol. (2006) [Pubmed]
  5. Structural mechanisms of QacR induction and multidrug recognition. Schumacher, M.A., Miller, M.C., Grkovic, S., Brown, M.H., Skurray, R.A., Brennan, R.G. Science (2001) [Pubmed]
  6. QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA. Grkovic, S., Brown, M.H., Roberts, N.J., Paulsen, I.T., Skurray, R.A. J. Biol. Chem. (1998) [Pubmed]
  7. Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus. Mayer, S., Boos, M., Beyer, A., Fluit, A.C., Schmitz, F.J. J. Antimicrob. Chemother. (2001) [Pubmed]
  8. Physical and biochemical characterization of the qacA gene encoding antiseptic and disinfectant resistance in Staphylococcus aureus. Tennent, J.M., Lyon, B.R., Midgley, M., Jones, I.G., Purewal, A.S., Skurray, R.A. J. Gen. Microbiol. (1989) [Pubmed]
  9. Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity. Bayer, A.S., Kupferwasser, L.I., Brown, M.H., Skurray, R.A., Grkovic, S., Jones, T., Mukhopadhay, K., Yeaman, M.R. Antimicrob. Agents Chemother. (2006) [Pubmed]
  10. Genetic linkage between resistance to quaternary ammonium compounds and beta-lactam antibiotics in food-related Staphylococcus spp. Sidhu, M.S., Heir, E., Sørum, H., Holck, A. Microb. Drug Resist. (2001) [Pubmed]
  11. Antiseptic susceptibility and distribution of antiseptic-resistance genes in methicillin-resistant Staphylococcus aureus. Noguchi, N., Hase, M., Kitta, M., Sasatsu, M., Deguchi, K., Kono, M. FEMS Microbiol. Lett. (1999) [Pubmed]
  12. Do biocides select for antibiotic resistance? Russell, A.D. J. Pharm. Pharmacol. (2000) [Pubmed]
  13. Identification and characterization of quaternary ammonium compound resistant staphylococci from the food industry. Heir, E., Sundheim, G., Holck, A.L. Int. J. Food Microbiol. (1999) [Pubmed]
  14. Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity. Paulsen, I.T., Brown, M.H., Littlejohn, T.G., Mitchell, B.A., Skurray, R.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Susceptibilities to antiseptic agents and distribution of antiseptic-resistance genes qacA/B and smr of methicillin-resistant Staphylococcus aureus isolated in Asia during 1998 and 1999. Noguchi, N., Suwa, J., Narui, K., Sasatsu, M., Ito, T., Hiramatsu, K., Song, J.H. J. Med. Microbiol. (2005) [Pubmed]
  16. Multidrug resistance to antiseptics and disinfectants in coagulase-negative staphylococci. Leelaporn, A., Paulsen, I.T., Tennent, J.M., Littlejohn, T.G., Skurray, R.A. J. Med. Microbiol. (1994) [Pubmed]
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