Inducible NorA-mediated multidrug resistance in Staphylococcus aureus.

Antimicrobial Agents and Chemotherapy
Glenn W Kaatz, S M Seo

Abstract

The NorA protein of Staphylococcus aureus mediates the active efflux of hydrophilic fluoroquinolones from the cell, conferring low-level resistance upon the organism. The protein also is capable of transporting additional structurally diverse compounds, indicating that it has a broad substrate specificity. Increased transcription of the norA gene, leading to a greater quantity of the NorA protein within the cytoplasmic membrane, is felt to be the mechanism by which strains possessing such changes resist fluoroquinolones. S. aureus SA-1199 and its in vivo-selected derivative SA-1199B are fluoroquinolone-susceptible and -resistant isolates, respectively; SA-1199B resists hydrophilic fluoroquinolones via a NorA-mediated mediated mechanism in a constitutive manner. SA-1199-3 is an in vitro-produced derivative of SA-1199 in which NorA-mediated multidrug resistance is expressed inducibly. Compared with organisms exposed to subinhibitory concentrations of a NorA substrate for the first time, preexposure of SA-1199-3 to such a compound followed by growth in the presence of that substrate results in the elimination of a 2- to 6-h period of organism killing that occurs prior to the onset of logarithmic growth. The uptake of radiolabeled ...Continue Reading

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