Elongation factor P controls ribosomal frameshift of an antimicrobial resistance gene in Salmonella Typhimurium [ugtL]

As the amino acid sequence directly dictates the activity of the protein, frameshift often leads to unwanted effects. Here, we demonstrate that the intracellular pathogen Salmonella Typhimurium suppresses frameshift in the ugtL antimicrobial resistance gene during translation.

This frameshift suppression is mediated by a ribosome pause occurring in a newly-identified overlapping gene, serving as a non-slip bump. Given that the pause site contains a poly-proline motif and can be resolved by elongation factor P, the removal of the ribosome pause by substituting the motif induces ribosome slippage in ugtL, resulting in nonfunctional UgtL frameshifted protein production. This renders Salmonella sensitive to antimicrobial peptides, indicating that elongation factor P-dependent ribosome pause is required for full antimicrobial resistance.