Disease relevance of qacA

• Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus: common ancestry with tetracycline- and sugar-transport proteins [1].
• Organization of the antiseptic resistance gene qacA and Tn552-related beta-lactamase genes in multidrug- resistant Staphylococcus haemolyticus strains of animal and human origins [2].
• The Staphylococcus epidermidis Fol62 isolate, harboring multiresistance plasmid pMS62, contained qacA/B and blaZ together with tetK [3].
• Therefore, it was concluded that the lower distribution rate of qacA/B resulted in higher susceptibilities to cationic antiseptic agents in MRSA isolated from patients with impetigo and SSSS [4].

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

• Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus [7].
• We have previously cloned a 3.5 kb fragment from the Staphylococcus aureus multiresistance plasmid pSK1 which carries the qacA determinant responsible for linked resistance to acriflavine (Acr), ethidium bromide (Ebr), quaternary ammonium compounds (Qar), propamidine isethionate (Pir), and diamidinodiphenylamine dihydrochloride (Ddr) [8].

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

• Site-directed mutagenesis of qacA confirmed the importance of an acidic residue within this region of QacA in conferring resistance to divalent cations [14].
• In addition, the distributions of the antiseptic-resistance genes qacA/B and smr were studied by PCR [15].
• Representative qacA and qacC plasmids were characterised by restriction endonuclease mapping, and were found to be similar in some cases, but different in others, to those plasmids on which these genes are found in S. aureus [16].

References