Convergent Evolution of Antibiotic Tolerance in Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia
Mitra Maria Elgrail, Edwin Chen, Marla G. Shaffer, Vatsala Rangachar Srinivasa, M. Patrick Griffith, Mustapha M. Mustapha, Ryan K. Shields, Daria Van Tyne, Matthew J. Culyba
Abstract
) were sampled at a low frequency from each patient but were detected in 10 (50%) of the patients. These results suggest that subpopulations of antibiotic-tolerant mutants emerge commonly during MRSA-PB. Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired infection. In severe cases, bacteria invade the bloodstream and cause bacteremia, a condition associated with high mortality. We analyzed the genomes of serial MRSA isolates derived from patients with bacteremia that persisted through active antibiotic therapy and found a frequent evolution of pathways leading to antibiotic tolerance. Antibiotic tolerance is distinct from antibiotic resistance, and the role of tolerance in clinical failure of antibiotic therapy is defined poorly. Our results show genetic evidence that perturbation of specific metabolic pathways plays an important role in the ability of MRSA to evade antibiotics during severe infection.