Methionyl-tRNA synthetase synthetic and proofreading activities are determinants of antibiotic persistence.

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon.

At the Crossroad of Nucleotide Dynamics and Protein Synthesis in Bacteria.

Nucleotides are at the heart of the most essential biological processes in the cell, be it as key protagonists in the dogma of molecular biology or by regulating multiple metabolic pathways. The dynamic nature of nucleotides, the cross talk between them, and their constant feedback to and from the cell's metabolic state position them as a hallmark of adaption toward environmental and growth challenges. It has become increasingly clear how the activity of RNA polymerase, the synthesis and maintenance of tRNAs, mRNA translation at all stages, and the biogenesis and assembly of ribosomes are fine-tuned by the pools of intracellular nucleotides.

Oxidative stress strongly restricts the effect of codon choice on the efficiency of protein synthesis in .

Introduction: The response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition.

Methods: In order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons.

Regulation of Leaderless mRNA Translation in Bacteria.

In bacteria, the translation of genetic information can begin through at least three different mechanisms: canonical or Shine-Dalgarno-led initiation, readthrough or 70S scanning initiation, or leaderless initiation. Here, we discuss the main features and regulation of the last, which is characterized mainly by the ability of 70S ribosomal particles to bind to AUG located at or near the 5' end of mRNAs to initiate translation. These leaderless mRNAs (lmRNAs) are rare in enterobacteria, such as , but are common in other bacteria, such as and where they may represent more than 20% and even up to 60% of the genes.

Initiator-Directed Transcription: Fission Yeast Nmtl Initiator Directs Preinitiation Complex Formation and Transcriptional Initiation.

The initiator element is a core promoter element encompassing the transcription start site, which is found in yeast, , and human promoters. This element is observed in TATA-less promoters. Several studies have defined transcription factor requirements and additional cofactors that are needed for transcription initiation of initiator-containing promoters.

Modulation of Translation by the Specific Inactivation of tRNA Under Oxidative Stress.

Bacterial oxidative stress responses are generally controlled by transcription factors that modulate the synthesis of RNAs with the aid of some sRNAs that control the stability, and in some cases the translation, of specific mRNAs. Here, we report that oxidative stress additionally leads to inactivation of tRNA in , inducing a series of physiological changes. The observed inactivation of tRNA correlated with altered efficiency of translation of Gly codons, suggesting a possible mechanism of translational control of gene expression under oxidative stress.

Codon usage revisited: Lack of correlation between codon usage and the number of tRNA genes in enterobacteria.

It is widely believed that if a high number of genes are found for any tRNA in a rapidly replicating bacteria, then the cytoplasmic levels of that tRNA will be high and an open reading frame containing a higher frequency of the complementary codon will be translated faster. This idea is based on correlations between the number of tRNA genes, tRNA concentration and the frequency of codon usage observed in a limited number of strains as well as from the fact that artificially changing the number of tRNA genes alters translation efficiency and consequently the amount of properly folded protein synthesized. tRNA gene number may greatly vary in a genome due to duplications, deletions and lateral transfer which in turn would alter the levels and functionality of many proteins.

Exposure to sub-inhibitory concentrations of cefotaxime enhances the systemic colonization of Salmonella Typhimurium in BALB/c mice.

It has been proposed that sub-inhibitory concentrations of antibiotics play a role in virulence modulation. In this study, we evaluated the ability of Salmonella enterica serovar Typhimurium (hereafter S. Typhimurium) to colonize systemically BALB/c mice after exposure to a sub-inhibitory concentration of cefotaxime (CTX).

The type VI secretion system encoded in Salmonella pathogenicity island 19 is required for Salmonella enterica serotype Gallinarum survival within infected macrophages.

Salmonella enterica serotype Gallinarum is the causative agent of fowl typhoid, a disease characterized by high morbidity and mortality that causes major economic losses in poultry production. We have reported that S. Gallinarum harbors a type VI secretion system (T6SS) encoded in Salmonella pathogenicity island 19 (SPI-19) that is required for efficient colonization of chicks.