Abstract
Stress promotes phenotypic changes in bacteria that allow them to survive antibiotic treatment. This phenomenon, termed antibiotic tolerance, can cause treatment failure, highlighting a need to define bacterial pathways that promote survival. Previously, we found Yersinia pseudotuberculosis downregulates tusB , a gene involved in modifying tRNAs with s (2) U, in response to doxycycline. Here we find that deletion of tusB results in loss of s (2) U and induces antibiotic tolerance. Using a combination of sequencing-based approaches and analysis of gene codon usage, our data show that loss of s (2) U decreases translation of ribosomal proteins. Ribosomal proteins are highly enriched in codons that require s (2) U-modified tRNAs for efficient translation, and loss of s (2) U results in ribosome pausing at these codons. Our results highlight a previously unknown mechanism of antibiotic tolerance where reduction in ribosomal protein abundance can globally reduce translation, and describes a novel strategy bacteria use to slow growth by modulating s (2) U levels.