Year: 2026
Type: preprint
Abstract: Summary Bacterial virulence genes exhibit distinctive codon usage that may impose tRNA-modification requirements for efficient translation, but a comprehensive understanding is lacking. Here, a curated codon-tRNA modification map for Salmonella predicted six modifications that could preferentially support virulence gene translation. Mutant phenotypes in infected mice confirmed requirements for i⁶A 37 and C 5 modification of U 34 , whereas essential k 2 C 34 could not be tested. Q 34 , Cm 32 /Um 32 , and Cm 34 had limited impact consistent with weak decoding effects in other systems. Non-predicted tRNA modifications were not required. Synonymous reporter variants, proteomics, and targeted recoding demonstrated that virulence-associated codons directly conferred modification dependence. Additionally, four Leu-TTA codons in ssrB , the master regulator of Salmonella pathogenicity island 2 (SPI-2), contributed to MiaA-dependent SPI-2 gene expression. Extending our analysis to other pathogens predicted shared and divergent virulence dependencies consistent with published mutant phenotypes. Thus, codon usage explains tRNA-modification requirements for bacterial virulence.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7212352811