The role of copper hemostasis in Staphylococcus aureus infection and antimicrobial resistance.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), gram-positive bacteria is one of the main opportunistic pathogens responsible for hospital-acquired and community-acquired, and livestock-associated infections worldwide. Treatment remains challenging to manage due to its ability to rapidly adapt to antibiotics. Although the fact that clinical overuse of antibiotics is highlighted as a major driver for the emergence of antibiotic resistance, other factors such as heavy metals may contribute to the virulence of S. aureus strains. Copper is a required micronutrient element for bacteria. However, copper can be extremely toxic when in excess. For survival, all bacteria developed copper resistance mechanisms. Importantly, the community-acquired Methicillin-resistant Staphylococcus aureus clone USA300 has also acquired a new copper resistance locus which may increase the fitness and virulence of these strains by increasing survival against the immune system, causing serious disease. Yet it is unclear how S. aureus adapts and survive the presence of excess copper. Here, we have investigated the global transcriptional response of S. aureus to copper stress and identified genes and pathways with the potential to be important for copper toxicity or resistance, and then we examined the role of the selected target gene in copper homeostasis. Collectively, our data showed that copper stress inhibits S. aureus growth and the expression of cwrA and cidB genes might be a response to copper toxicity or resistance. We also found that copL, a novel lipoprotein, that confers copper hyper-resistance has no role in the regulation cwrA and cidB genes.