Novel insight into antimicrobial resistance and sensitivity phenotypes associated to qac and norA genotypes in Staphylococcus aureus

Staphylococcus aureus strains harboring QacA, QacB, QacC, QacG transporters and norA promoterup-regulating mutations were characterized by phenotype microarray (PM), standard methods forsusceptibility testing, and ethidium bromide efflux assays, in order to increase knowledge on phen-otypes associated to efflux pumps and their substrates. PM data and standard susceptibility testinglead to the identification of new potential efflux targets, such as guanidine hydrochloride or 8-hydroxyquinoline for QacA and QacC pumps, respectively. The identification of compounds to which thepresence of efflux pumps induced increased susceptibility opens new perspectives for potential adjunctanti-resistance treatment (i.e. strains bearing QacB transporters showed increased susceptibility to thior-idazine, amitriptyline and orphenadrine). Although the tested isolates were characterized by high degreeof heterogeneity, a hallmark of clinical isolates, direct ethidium bromide efflux assays were effective inhighlighting differences in efflux efficiency among strains. These data add to characterization of substratespecificity in the different classes of staphylococcal multidrug efflux systems conferring specific substrateprofiles and efflux features to each of them.