Core Concepts
Queuosine (Q) modification of tRNA-Tyrosine by the Tgt enzyme modulates the efficiency of tyrosine codon decoding, leading to translational reprogramming that enhances Vibrio cholerae's growth and tolerance in the presence of sub-lethal aminoglycoside concentrations.
Abstract
The study investigates how the queuosine (Q) modification of tRNA-Tyrosine by the Tgt enzyme impacts Vibrio cholerae's response to aminoglycoside antibiotics. Key findings:
Deletion of the tgt gene in V. cholerae (Δtgt) leads to decreased growth and tolerance in the presence of sub-lethal concentrations of the aminoglycoside tobramycin (TOB), but not other antibiotics like ciprofloxacin or carbenicillin.
The growth defect of Δtgt is not due to increased antibiotic uptake or changes in proton-motive force. Overexpression of tRNA-Tyr with the native GUA anticodon, but not a synthetic AUA anticodon, restores the growth defect in TOB.
Using molecular reporters, proteomics, and RNA-seq, the authors show that the Q modification impacts the efficiency of decoding at tyrosine TAT and TAC codons. The anti-SoxR factor RsxA, which has a codon bias towards TAT, is more efficiently translated in the absence of tgt. This leads to decreased expression of genes in the SoxR oxidative stress regulon.
Bioinformatic analysis identified other candidate genes with TAT codon bias, including DNA repair factors, that may be subject to translational regulation by the Q modification in response to antibiotic stress.
The authors propose that regulation of Q modification in response to environmental cues, such as sub-lethal antibiotic levels, leads to translational reprogramming of genes with biased tyrosine codon usage, allowing the bacteria to better adapt to the stress.
Stats
The Δtgt strain shows decreased survival compared to WT after treatment with lethal concentrations of tobramycin (TOB) for 15 minutes to 4 hours, but not with ciprofloxacin (CIP) or carbenicillin (CRB).
The Δtgt strain does not show differences in proton-motive force or neomycin uptake compared to WT.
Quotes
"Queuosine (Q) modification of tRNA-Tyrosine by the Tgt enzyme modulates the efficiency of tyrosine codon decoding, leading to translational reprogramming that enhances Vibrio cholerae's growth and tolerance in the presence of sub-lethal aminoglycoside concentrations."
"We propose that regulation of Q modification in response to environmental cues, such as sub-lethal antibiotic levels, leads to translational reprogramming of genes with biased tyrosine codon usage, allowing the bacteria to better adapt to the stress."