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

Abstract

NorA is the best studied efflux system of Staphylococcus aureus 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 S. aureus. Genetic diversity studies of the gene norA have described three alleles; norAI, norAII and norAIII. However, the epidemiology of these alleles and their impact on NorA activity remains unclear. Additionally, increasing studies do not account for norA variability when establishing relations between resistance phenotypes and norA presence or reported absence, which actually corresponds, as we now demonstrate, to different norA alleles. In the present study we assessed the variability of the norA gene present in the genome of over 1,000 S. aureus isolates, corresponding to 112 S. aureus 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 norA is part of the core genome of S. aureus. It also suggests that occurrence of norA variants reflects the population structure of this major pathogen. Overall, this work highlights the ubiquitous nature of norA in S. aureus which must be taken into account when studying the role played by this important determinant on S. aureus resistance to antimicrobials.