Mechanism of quinolone resistance in Staphylococcus aureus

Molecular Characterization of Fluoroquinolone Resistance of Methicillin –Resistant Clinical Staphylococcus aureus Isolates from Rawalpindi, Pakistan

“…G291D confers a stabilizing effect due to a predicted G of 0.48 kcal/mol and its presence along with a deletion in the promoter region of the norA gene, possibly results in a fitness advantage for G291D clones. Of the two novel point mutations observed within the norA gene in this study, G291D is distant from the putative substratebinding sites but V371 is within the second binding site known as "Walker B" site, it is neither involved in hydrogen bonding nor hydrophobic interactions [32]. Therefore, a V371I mutation probably exhibited no change in the expression of norA, norB, norC, and mdeA.…”

“…4). Of these five isolates, isolate10 had a novel point mutation (V371I) within the norA coding region and the other four isolates (30,32,35, and 41) had another novel point mutation (G291D). …”

Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use

“…Of note, two nonsynonymous SNPs in the C02 gyrA and grlA genes (C251T and T239A, respectively) were detected. These SNPs result in an S84L amino acid mutation in GyrA and an F80Y mutation in GrlA, which have previously been shown to contribute to quinolone resistance (15)(16)(17) and therefore likely explain the levofloxacin resistance of the C02 isolate.…”

Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

“…The best available screen consists of MIC determinations with and without pump inhibitors, but the contributions of other resistance mechanisms may obscure inhibitor-related MIC decreases. An example of this situation is fluoroquinolone resistance related to topoisomerase mutations in a strain overexpressing the NorA MDR pump, where the comparatively small contribution of efflux can be overshadowed by large MIC increases associated with target mutations (11,28).…”

“…The widespread distribution of Qac proteins, which mediate resistance to biocides, in 40% of methicillin-resistant S. aureus (MRSA) strains in Europe and Asia underscores their clinical relevance in those regions (1,21,25). However, similar studies with respect to NorA have examined only the effect of reserpine on MICs and the sequence of norA and its promoter (23,24,27,28). None of these studies evaluated norA mRNA abundance.…”