Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance

Bacteria can adapt to a changing environment by adopting alternate metabolic states favoring small molecule synthesis and resilience over growth. In Staphylococcus aureus, these states are induced by factors present during infection, including nutritional limitations, host responses and competition with other bacteria. Isogenic tolerant populations have variable responses to antibiotics and can remain viable. In this study, we compared the capability of antibiotics to reduce the viability of S. aureus made tolerant by different mechanisms. Tolerance was induced with mupirocin, HQNO, peroxynitrite or human serum. Tolerant cultures were exposed to ceftaroline, daptomycin, gentamicin, levofloxacin, oritavancin or vancomycin at physiological concentrations, and the viability was assessed by dilution plating. The minimum duration for 3-log viability reduction and 24 h viability reduction were calculated independently for each of three biological replicates. Each tolerance mechanism rendered at least one antibiotic ineffective, and each antibiotic was rendered ineffective by at least one mechanism of tolerance. Further studies to evaluate additional antibiotics, combination therapy and different tolerance inducers are warranted.

Automated summary

This study compared the effects of different mechanisms of tolerance induction on the effectiveness of antibiotics against Staphylococcus aureus. It was found that each mechanism of tolerance rendered at least one antibiotic ineffective, and each antibiotic was rendered ineffective by at least one mechanism of tolerance. Further research is needed to evaluate additional antibiotics, combination therapy, and different tolerance inducers.