BACKGROUND: The ubiquitous
bacterial trans-translation is one of the most studied
quality control mechanisms. Trans-translation requires two specific factors, a small
RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of
ribosomes stalled on defective
mRNAs and to add a specific tag sequence to aberrant
polypeptides to direct them to degradation pathways.
Helicobacter pylori is a
pathogen persistently colonizing a hostile niche, the
stomach of humans. PRINCIPAL FINDINGS: We investigated the role of trans-translation in this
bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five
mutant versions of ssrA were generated in
H. pylori in order to investigate the function of trans-translation in this organism.
Mutation of the resume
codon that allows the switch of template of the
ribosome required for its release was essential in vivo, however a
mutant in which this
codon was followed by
stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled
ribosomes. A
mutant expressing a truncated
SsrA tag was viable in
H. pylori, but affected in competence and tolerance to both oxidative and
antibiotic stresses. This demonstrates that control of
protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of
H. pylori. CONCLUSIONS: We conclude to a central role of trans-translation in
H. pylori both for
ribosome rescue possibly due to more severe stalling and for
protein degradation to recover from stress conditions frequently encountered in the
gastric environment. Finally, the essential trans-translation machinery of
H. pylori is an excellent specific target for the development of novel
antibiotics.
