Evidence for the Existence of a Multidrug Efflux Transporter Distinct from NorA in Staphylococcus aureus

Abstract

A Staphylococcus aureus norA disruption mutant was created by allelic replacement. Exposure of this mutant to norfloxacin produced SA K1748, a derivative with raised fluoroquinolone MICs, found to be the result of a grlA mutation, and raised organic cation MICs. Ethidium and enoxacin uptake was identical in SA K1748 and its parent, but pre-exposure of SA K1748 to organic cations caused a reduction in ethidium uptake as a result of increased efflux. Altered ethidium uptake and efflux, as well as increased MICs of other organic cations, suggest that SA K1748 possesses a non-NorA multidrug efflux transporter that is inducible by its substrates.

Frequency and Genetic Characterization of Multidrug-Resistant Mutants of Staphylococcus aureus after Selection with Individual Antiseptics and Fluoroquinolones.

“…However, these mutants exhibited no mutations in the norA promoter and in the QRDRs in the grlA and gyrA genes, as was the case for mutant obtained previously. 15) These results therefore indicate the existence of another gene(s) on the S. aureus chromosome, in addition to norA, that is related to multidrug-resistance.…”

Interactions of the QacR Multidrug-Binding Protein with Structurally Diverse Ligands: Implications for the Evolution of the Binding Pocket

“…All cloning and overexpression procedures performed in Escherichia coli utilized strain DH5R (26), whereas two S. aureus strains were employed, RN4220 (27) and the norA multidrug efflux pump determinant knockout SAK1712 (28). Unless stated otherwise, all strains were cultured at 37°C in Luria-Bertani broth or agar (26) containing, where appropriate, 100 µg mL -1 ampicillin for E. coli and 50 µg mL -1 ethidium, 25 µg mL -1 gentamicin, 3 µg mL -1 tetracycline, or 100 µg mL -1 trimethoprim for S. aureus.…”

Pseudoalteromonas phenolica sp. nov., a novel marine bacterium that produces phenolic anti-methicillin-resistant Staphylococcus aureus substances

“…The high prevalence of MRSA around the world makes it a serious public health problem, since this Gram-positive pathogen has become multi-drug-resistant (Archer & Bosilevac, 2001;Hiramatsu et al, 2001;Isnansetyo et al, 2001;Kaatz et al, 2000;Witte, 1999). In an effort to discover alternative antibiotics against MRSA, we screened bacteria that originated from the marine environment for anti-MRSA activity.…”