The (p)ppGpp-mediated stringent response. (A) Low amino acid concentrations lead to decreased charging of the corresponding tRNAs. (B) The translational machinery depends on the translocation along the mRNA whereby a new acetylated-tRNA is positioned in the ribosome. Whenever an uncharged tRNA binds to the ribosome, the elongation of the polypeptide chain is stalled. (C) The stringent factor RelA is then activated in the presence of the ribosomal protein L11, catalyzing the synthesis of (p)ppGpp nucleotides. (D) These nucleotides bind directly to the RNA polymerase and affect the binding abilities of sigma factors to the core RNA polymerase. (E) The cofactor DksA also binds to the RNA polymerase and augments the (p)ppGpp regulation of the transcription initiation at certain σ70-dependent promoters, functioning both as negative and positive regulators. (F) These regulators change the gene expression: (i) decreasing the transcription activity of genes involved in translational activities; (ii) and increasing the transcription of stress-related operons and genes encoding for enzymes needed for the synthesis and the transport of amino acids.