AUTHOR=Costa Sofia Santos , Sobkowiak Benjamin , Parreira Ricardo , Edgeworth Jonathan D. , Viveiros Miguel , Clark Taane G. , Couto Isabel 

TITLE=Genetic Diversity of norA, Coding for a Main Efflux Pump of Staphylococcus aureus

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00710

DOI=10.3389/fgene.2018.00710

ISSN=1664-8021

ABSTRACT=<p>NorA is the best studied efflux system of <italic>Staphylococcus aureus</italic> and therefore frequently used as a model for investigating efflux-mediated resistance in this pathogen. NorA activity is associated with resistance to fluoroquinolones, several antiseptics and disinfectants and several reports have pointed out the role of efflux systems, including NorA, as a first-line response to antimicrobials in <italic>S. aureus</italic>. Genetic diversity studies of the gene <italic>norA</italic> have described three alleles; <italic>norAI</italic>, <italic>norAII</italic> and <italic>norAIII</italic>. However, the epidemiology of these alleles and their impact on NorA activity remains unclear. Additionally, increasing studies do not account for <italic>norA</italic> variability when establishing relations between resistance phenotypes and <italic>norA</italic> presence or reported absence, which actually corresponds, as we now demonstrate, to different <italic>norA</italic> alleles. In the present study we assessed the variability of the <italic>norA</italic> gene present in the genome of over 1,000 <italic>S. aureus</italic> isolates, corresponding to 112 <italic>S. aureus</italic> strains with whole genome sequences publicly available; 917 MRSA strains sourced from a London-based study and nine MRSA isolates collected in a major Hospital in Lisbon, Portugal. Our analyses show that <italic>norA</italic> is part of the core genome of <italic>S. aureus.</italic> It also suggests that occurrence of <italic>norA</italic> variants reflects the population structure of this major pathogen. Overall, this work highlights the ubiquitous nature of <italic>norA</italic> in <italic>S. aureus</italic> which must be taken into account when studying the role played by this important determinant on <italic>S. aureus</italic> resistance to antimicrobials.</p>