Contribution of Ionophores to Clinical Antimicrobial Resistance

Antimicrobial resistance (AMR) contributes to approximately 700,000 deaths worldwide each year, and this number increases annually. The use of antimicrobials in animals is an increasing concern in the spread of AMR. Ionophores are a class of antibiotic widely used in veterinary medicine for growth promotion and disease prevention, but they are not seen as a contributor to clinical AMR. Nonetheless, mechanisms of resistance to ionophores and their relation to clinical AMR are not well understood. To address these questions, we evolved the opportunistic pathogens Staphylococcus epidermidis and Staphylococcus aureus in the presence or absence of ionophores in the lab. We then assayed resistance to ionophores and to conventional medically important antimicrobials (MIAs). Ionophore resistance was found in S.epidermidis, but not in S.aureus. Collateral sensitivity and cross-resistance were also found in S.epidermidis, while S.aureus showed only a decrease in sensitivity toward some MIAs.