Adaptive Laboratory Evolution of Staphylococcus aureus

Antimicrobial resistance (AMR) is one of the greatest threats against human health and the misuse and overuse of antibiotics is a key factor driving resistance development. During prolonged antibiotic treatment of chronic infections, the antimicrobial pressure facilitates selection of AMR mutations. It has been suggested that using antibiotics in combinations may reduce the emergence of AMR. Furthermore, antibiotic tolerant persister cells may be a reservoir for AMR development, so targeting persister cells with anti-persister drugs could also reduce the emergence of resistance. We performed adaptive laboratory evolution study on the human opportunistic pathogen, Staphylococcus aureus, to assess which antibiotics are less prone to lead to AMR. The goal was to investigate if antibiotic combination therapy could prevent or delay the development of AMR compared with antibiotic monotherapy. Furthermore, we tested if prolonged treatment with the anti-persister drug, mitomycin C, did not lead to AMR against it self and other antimicrobials.After subjecting triplicates of S. aureus to increasing concentrations (relative to how resistance increased) of either mitomycin C, vancomycin, ciprofloxacin, daptomycin, rifampicin, micomycin C + rifampicin, vancomycin + rifampicin, ciprofloxacin + rifampicin or daptomycin + rifampicin for 42 consecutive days we sequenced the mutants as well as the parent (pre-evolution). Here we publish the genomes of the parent triplicates (S. aureus ATCC 29213) as well as the triplicates for all mutants (27 in total).