journals.asm.org
Inactivation of a purine biosynthesis repressor promotes ribosome synthesis to overcome antibiotic stress | mBio
The Erm rRNA methyltransferase superfamily represents the most prevalent determinant of MLS resistance in nosocomial Gram-negative and Gram-positive bacteria. Previous studies have established that erm expression is primarily governed by upstream ribosome stalling peptide and the 5′ untranslated regions. Using the widespread S. aureus ermBL-ermB (ermB+) operon as a model system, we unexpectedly identified second-site mutations in purR that synergistically enhance MLS resistance in an ermB+ background. Loss of purR function derepresses nucleotide biosynthesis and ribosome production, thereby promoting bacterial growth under antibiotic stress. While numerous purR single-nucleotide polymorphisms across multiple species have been associated with antibiotic resistance, no study has directly linked these sequence polymorphisms to their regulatory function. Our results highlight the critical role of ribosome abundance and nucleotide metabolism in shaping antibiotic efficacy.
