Resistance to Antimicrobials Mediated by Efflux Pumps in Staphylococcus aureus

Abstract

Resistance mediated by efflux has been recognized in Staphylococcus aureus in the last few decades, although its clinical relevance has only been recognized recently. The existence of only a few studies on the individual and overall contribution of efflux to resistance phenotypes associated with the need of well-established methods to assess efflux activity in clinical isolates contributes greatly to the lack of solid knowledge of this mechanism in S. aureus. This study aims to provide information on approaches useful to the assessment and characterization of efflux activity, as well as contributing to our understanding of the role of efflux to phenotypes of antibiotic resistance and biocide tolerance in S. aureus clinical isolates. The results described show that efflux is an important contributor to fluoroquinolone resistance in S. aureus and suggest it as a major mechanism in the early stages of resistance development. We also show that efflux plays an important role on the reduced susceptibility to biocides in S. aureus, strengthening the importance of this long neglected resistance mechanism to the persistence and proliferation of antibiotic/biocide-resistant S. aureus in the hospital environment.

Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections

“…9 The antihypertensive drug, verapamil has been shown to be an inhibitor the ABC class of pumps in Gram-positive bacteria such as Staphylococci and verapamil has been demonstrated to inhibit efflux pumps in S. aureus . 10,11 We therefore evaluated the effect of verapamil on the observed MIC for several key compounds. MICs were determined for S. aureus ATCC92953 in the absence and presence of verapamil (200 mg/L, a concentration previously reported as an optimal sub-inhibitory concentration 11 ).…”

“…10,11 We therefore evaluated the effect of verapamil on the observed MIC for several key compounds. MICs were determined for S. aureus ATCC92953 in the absence and presence of verapamil (200 mg/L, a concentration previously reported as an optimal sub-inhibitory concentration 11 ). Vancomycin was used as control and gave the same MIC (2 μg/ml) in presence and absence of verapamil as did compound 10d (MIC = 0.5 μg/ml).…”

“…A sub-inhibitory concentration of verapamil (200 mg/L) 11 was added to CAMHB and all assays were preformed as described above with either CAMHB or CAMHB containing verapamil (vCAMHB). Culture plates were then incubated for 18–24 h at 37 LC and the optical density at 600 nm (OD 600 ) was measured using the PowerWave™ XS (BioTek).…”

Does the presence of QAC genes in staphylococci affect the efficacy of disinfecting solutions used by orthokeratology lens wearers?

“…QAC genes encode multidrug efflux pumps, which are membrane proteins capable of exporting many biocides out of cells 21 22. The presence of two QAC genes has been shown to lead to smaller log reductions than isolates having only one gene, which may be due to additive effects of efflux pumps.…”

Efflux as an Arising Cause of Drug Resistance in E. Coli.

“…The Etbr-agar cartwheel assay method was used to assess the presence of efflux activity in E.coli strains following the methodology of with slight modifications [28][29][30] . All the strains of E.coli were grown in nutrient broth and incubated at 37°C for 24 hours.…”