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.
Highlights
Efflux pumps are membrane proteins that have the function of detoxifying cells by expelling noxious molecules [1]
The EtBr-agar cartwheel (EtBrCW) method is a practical methodology to assess the presence of increased efflux activity in large collections of clinical isolates of different bacterial species [12]
EtBr and the minimum inhibitory concentrations (MICs) determination in the presence of efflux inhibitors allowed the correlation of this efflux activity with resistance to fluoroquinolones and some biocides, including quaternary ammonium compounds and chlorhexidine, antimicrobials widely used in healthcare settings
Summary
Efflux pumps are membrane proteins that have the function of detoxifying cells by expelling noxious molecules [1]. Efflux pumps present different substrate specificities; some are specific to an antibiotic or a class of antibiotics, whereas multidrug efflux pumps, as the name implies, have the capacity to extrude more than one class of antibiotics and/or other antimicrobial compounds [5]. These latter efflux systems are of foremost relevance, since they can bestow the bacterial cell with a phenotype of resistance to multiple drugs in addition to promoting cross-resistance between antibiotics and other antimicrobial compounds usually used to prevent and control healthcare associated infections [4]. Specific efflux pumps can be found either in the chromosome or in plasmids, while multidrug efflux pumps are mainly located in the chromosome, with the exception of QacA/B and Smr, which have only been described in plasmids [5]
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