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

Staphylococcus aureus is one of the major human pathogens at both nosocomial and community level. Reduced susceptibility to antiseptics and disinfectants based on quaternary ammonium compounds (QACs) is widespread among staphylococci. Reduced susceptibility to QACs is often associated to the presence of plasmid encoded efflux pumps or to up-regulation of the chromosomal NorA pump. Four different qac genes, including qacA, qacB, the genes for the smr pumps QacC and QacG are found in clinical isolates. In order to deepen the knowledge on responses associated to different efflux pumps and to identify new potential efflux substrates, we applied the Phenotype Microarray (PM) high-throughput technology to compare the metabolic activity of S. aureus strains bearing qacA, qacB, qacC and qacG determinants or up-regulating mutations in the norA promoter in comparison with strains bearing no resistance markers. PM allows to test the chemical sensitivity patterns, analyzing metabolic activity, in presence of 240 different antimicrobial compounds, each one at 4 concentrations. Collected data allowed a deeper characterization of tested efflux pumps, leading to the identification of new potential efflux targets for both Qac and NorA transporters. Furthermore compounds to which the presence of efflux pumps induced increased susceptibility were identified, opening new perspectives for the development of more effective antimicrobial treatments.