Convergent Evolution of Antibiotic Tolerance in Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia.

ABSTRACT: Severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are often complicated by persistent bacteremia (PB) despite active antibiotic therapy. Antibiotic resistance rarely contributes to MRSA-PB, suggesting an important role for antibiotic tolerance pathways. To identify bacterial factors associated with PB, we sequenced the whole genomes of 206 MRSA isolates derived from 20 patients with PB and looked for genetic signatures of adaptive within-host evolution. We found that genes involved in the tricarboxylic acid cycle (citZ and odhA) and stringent response (rel) bore repeated, independent, protein-altering mutations across multiple infections, indicative of convergent evolution. Both pathways have been linked previously to antibiotic tolerance.

SUBMITTER: Elgrail MM 

PROVIDER: S-EPMC9022596 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature