RNA Sequencing Identifies a Common Physiology in Vancomycin- and Ciprofloxacin-Tolerant Staphylococcus aureus Induced by ileS Mutations

Abstract

Little is known about the mechanisms by which ileS mutations induce vancomycin tolerance in Staphylococcus aureus This study showed that transcriptome profiles were similar in vancomycin-tolerant mutants and the IleRS-inhibitor-treated parent. Notably, ileS and relA, which induce a stringent response, were upregulated. The same mechanism was responsible for cross-tolerance to vancomycin and ciprofloxacin. These findings suggest that the accumulation of uncharged isoleucyl-tRNA following ileS mutations in S. aureus was responsible for drug tolerance.

Keywords: RNA sequencing; S. aureus; cross-tolerance; ileS mutants; stringent response; transcriptome; vancomycin tolerance.