Codon usage determines tRNA-modification requirements for bacterial virulence
Abstract
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 iA37 and C5 modification of U34, whereas essential k2C34 could not be tested. Q34, Cm32/Um32, and Cm34 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.
Related
- The La Crosse virus M segment determines virus isolate cell-to-cell spread and virulence
- Sex-specific regulation of macrophage function determines outcome to acute bacterial infection
- Surface architecture of the bacterial envelope determines phage adsorption route in pathogenic Escherichia coli O157:H7
- Hopeaphenol targets histidine kinase signaling across kingdoms to suppress bacterial virulence and potentiate plant immunity
- The small molecule regacin binds a conserved pocket in RegA to inhibit the expression of bacterial virulence factors
BibTeX
@misc{goormaghtigh2026codon,
title = {{Codon usage determines tRNA-modification requirements for bacterial virulence}},
author = {F. Goormaghtigh and M. Antelo Varela and D. Bumann},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750475},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750475v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Codon usage determines tRNA-modification requirements for bacterial virulence
AU - F. Goormaghtigh
AU - M. Antelo Varela
AU - D. Bumann
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750475
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750475v1
AB - 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 iA37 and C5 modification of U34, whereas essential k2C34 could not be tested. Q34, Cm32/Um32, and Cm34 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.
ER -