title: Novel insight into antimicrobial resistance and sensitivity phenotypes associated to qac and norA genotypes in Staphylococcus aureus.
abstract: Staphylococcus aureus strains harboring QacA, QacB, QacC, QacG transporters and norA promoter up-regulating mutations were characterized by phenotype microarray (PM), standard methods for susceptibility testing, and ethidium bromide efflux assays, in order to increase knowledge on phenotypes associated to efflux pumps and their substrates. PM data and standard susceptibility testing lead 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 the presence of efflux pumps induced increased susceptibility opens new perspectives for potential adjunct anti-resistance treatment (i.e. strains bearing QacB transporters showed increased susceptibility to thioridazine, amitriptyline and orphenadrine). Although the tested isolates were characterized by high degree of heterogeneity, a hallmark of clinical isolates, direct ethidium bromide efflux assays were effective in highlighting differences in efflux efficiency among strains. These data add to characterization of substrate specificity in the different classes of staphylococcal multidrug efflux systems conferring specific substrate profiles and efflux features to each of them.
authors: Dipartimento di Scienze delle Produzioni Agroalimentari e dell'Ambiente (DiSPAA), Università di Firenze, Piazzale delle Cascine, 18, Firenze, FI, Italy.
authors: Emmanuela
authors: E
authors: Marchi
authors: LAMMB, Dipartimento di Biotecnologie, Università di Siena, Policlinico Le Scotte (lotto 5, piano 1), Siena, SI, Italy.
authors: Leonardo
authors: L
authors: Furi
authors: Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente, via Mangiagalli, 25, Milano, MI, Italy.
authors: Stefania
authors: S
authors: Arioli
authors: Quotient Bioresearch, Newmarket Road, Fordham Cambridgeshire CB7 5WW, UK; IHMA Europe Sàrl, Route de la Corniche 9A, Epalinges, Switzerland.
authors: Ian
authors: I
authors: Morrissey
authors: Quotient Bioresearch, Newmarket Road, Fordham Cambridgeshire CB7 5WW, UK; IHMA Europe Sàrl, Route de la Corniche 9A, Epalinges, Switzerland.
authors: Valeria
authors: V
authors: Di Lorenzo
authors: Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente, via Mangiagalli, 25, Milano, MI, Italy.
authors: Diego
authors: D
authors: Mora
authors: Dipartimento di Scienze delle Produzioni Agroalimentari e dell'Ambiente (DiSPAA), Università di Firenze, Piazzale delle Cascine, 18, Firenze, FI, Italy.
authors: Luciana
authors: L
authors: Giovannetti
authors: LAMMB, Dipartimento di Biotecnologie, Università di Siena, Policlinico Le Scotte (lotto 5, piano 1), Siena, SI, Italy; Department of Genetics, University of Leicester, Adrian Building, University Road, Leicester, LE1 7RH, UK.
authors: Marco Rinaldo
authors: MR
authors: Oggioni
authors: Dipartimento di Scienze delle Produzioni Agroalimentari e dell'Ambiente (DiSPAA), Università di Firenze, Piazzale delle Cascine, 18, Firenze, FI, Italy. Electronic address: carlo.viti@unifi.it.
authors: Carlo
authors: C
authors: Viti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D016000:Cluster Analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010641:Phenotype; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus; C068498:qacA protein, Staphylococcus aureus
keywords: Multidrug resistance; NorA promoter mutations; Phenotype microarray; QAC transporters; Staphylococcus aureus