Second, trans-translation

functions to direct incomplete peptides to degradation by the addition of a specific tag [4]. Trans-translation is generally non-essential and requires two factors: SsrA, a small stable structured RNA (also called tmRNA) that acts both as a tRNA by its alanylated selleck chemical tRNA-like domain (TLD) and as a mRNA-like domain (MLD) [4] and its protein cofactor, SmpB. The length and sequence of the trans-translation appended peptide tag varies with the bacterial species (between 8 and 35 amino acids) [5]. Mostly studied in E. coli, the tag encoded by SsrA is sufficiently informative to target any trans-translated proteins to degradation pathways [4]. The phenotypes of mutants deficient in this process depend on the species examined and are related to environmental adaptation, differentiation, stress response or www.selleckchem.com/products/BEZ235.html virulence (for a review see [6]). Growing evidence indicates that trans-translation tagging targets specific substrates and therefore plays a regulatory role in organisms such as Caulobacter crescentus

[7, 8]Yersinia pseudotuberculosis [9], Helicobacter pylori [10] or Streptomyces coelicolor [11]. In E. coli, numerous buy SIS3 phenotypes were associated with the deficiency of trans-translation, among which a slight enhancement of the doubling time that was observed even under normal growth conditions [12]. One of the tools used to characterize the SsrA determinants in vivo was the dependence Selleck 5-Fluoracil on trans-translation of the growth of the hybrid bacteriophage λimm P22 in E. coli [13–15]. This phage is a hybrid between

the E. coli lambda phage and the Salmonella P22 phage and is specific for E. coli. E. coli strains defective in trans-translation display a characteristic phenotype termed “”Sip”" (for selectively inhibits of λimm P22) [13]. Indeed, the frequency of infection by λimm P22 is 10,000-fold lower in ΔsmpB or ΔssrA E. coli mutants as compared to that in the corresponding parental strain [13, 16]. The precise molecular basis of the phage plating defect in trans-translation-deficient cells is not yet understood. The impact of SsrA point mutations on λimm P22 growth in E. coli was first analyzed by Withey and Friedman [14] who showed (i) that charging of tmRNA with Ala was essential and, (ii) that degradation of proteins tagged by tmRNA was only required to achieve optimal levels of phage growth. A more recent study challenged these conclusions and demonstrated that λimm P22 propagation in E. coli is exclusively dependent on ribosome recycling functions of trans-translation and not on its proteolysis targeting activity [15]. We have recently investigated the role of trans-translation in Helicobacter pylori [10]. H. pylori is a bacterial pathogen that colonizes the stomach of half of the human population and is strongly adapted to persist and multiply under stressful conditions such as low pH. Colonization of the stomach by H.