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Category: Microbial Genetics and Molecular Biology
Sigma Factors: Key Molecules in Mycobacterium tuberculosis Physiology and Virulence, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap07-2.gifAbstract:
Rapid adaptation to changing environments is one of the keys of the success of microorganisms. Such adaptation is achieved by enabling different strategies, the most potent of which is global transcriptional modulation. Bacterial genomes encode several transcriptional regulators that in response to external and internal stimuli rapidly change the transcriptional profile of the cells, allowing maintenance of the homeostasis. Among the several players responsible for global transcriptional regulation, sigma (σ) factors have a prominent role ( 1 ). These are small interchangeable subunits of the RNA polymerase (RNAP) holoenzyme that are required for transcriptional initiation and that determine the promoter specificity of the enzyme recognizing specific −35 and −10 consensus promoter sequences ( 2 ). All bacterial genomes encode at least one essential σ factor, responsible for the transcription of housekeeping genes, and a variable number of alternative σ factors enabling a rapid transcriptional shift in response to specific stimuli ( 3 , 4 ).
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Sequence of the region immediately upstream of the sigB translational stat codon. (A) White box indicates MprA binding sites. Gray letters indicate residues protected by MprA ( 55 , 56 ); light gray box indicates the putative σF-dependent promoter; dark gray box indicates the σE, σH, and σL putative promoter. −35 and −10 sequences are underlined. Transcriptional start points are shown in capital letters. (B) Putative consensus sequences recognized by the four σ factors ( 53 ). Modified from reference 51 .
Comparison of conserved domains and multidomains in M. tuberculosis Rv0093c and M. avium σC. zf-HC2, Putative zinc-finger found in some anti-σ factor proteins; COG5660, predicted integral membrane protein; PRK09649, RNA polymerase sigma factor σC; Sigma70_r2, σ70 region 2; Sigma70_r4, σ70 region 4. Alignments were performed at http://blast.ncbi.nlm.nih.gov/Blast.cgi.
Alignment of M. avium σC (black) with M. tuberculosis Rv0093c (green) and σC (red).
Sequence of the sigE upstream region and of the first part of the sigE coding region in M. tuberculosis containing the three promoters and the translational start sites of its three isoforms. Transcription start points are shown in capital letters, and putative −10 and −35 are underlined. MprA binding sites are boxed. Letters in gray indicate residues protected by MprA binding ( 55 , 56 ). Putative translation start codons are shown in boxed capital letters, while the putative ribosome binding site (RBS) is shown in boxed plain letters. The two arrows show the 9-bp duplication (ATCACGACC) found in the M. tuberculosis complex genomes. Modified from reference 83 .
The σE network. (A) Surface stress promotes PknB-dependent phosphorylation of RseA, leading to cleavage by ClpC1P2, which results in activation of the σE regulon. σE controls transcription of clgR, which in turn induces the clp regulon. An increase in ClpC1P2 levels leads to increased RseA degradation and a higher concentration of free σE (positive feedback loop) ( 86 ). σE also controls transcription of ppk1: Increased PPK1 levels raise PolyP concentration, which controls sigE transcription through MprB-dependent phosphorylation of MprA (positive feedback loop) ( 85 ). Also, a σE-dependent promoter drives mprAB transcription (positive feedback loop) ( 36 ). Finally, sigE is subject to autoregulation (Chauhan and Gennaro, personal communication). Solid, dashed, and curved arrows represent transcriptional regulation, protein production, and catalytic reactions, respectively. (B) Abstraction of feedback loops discussed in panel (A). Modified from reference 12 .
Main regulatory network responsible for SigF regulation. Arrows indicate transcriptional regulation; truncated lines indicate posttranslational regulation. At least four other proteins—Rv0516c, Rv1364c, Rv1904, and RV2638—have been hypothesized to be involved in this network, but their role has not been elucidated yet.
Regulatory network of σ factors. Arrows indicate transcriptional regulation; truncated lines indicate posttranslational regulation. The role of σF is still putative. SS, surface stress; LP, low phosphate; OS, oxidative stress.
M. tuberculosis σ factors