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Evidence of complex transcriptional, translational, and posttranslational regulation of the extracytoplasmic function sigma factor sigmaE in Mycobacterium tuberculosis.

ABSTRACT: The extracytoplasmic factor (ECF) sigma factor sigma(E) is one of the most studied sigma factors of Mycobacterium tuberculosis. It has been shown to be involved in virulence as well as in survival under conditions of high temperature, alkaline pH, and exposure to detergents and oxidative stress. Unlike many ECF sigma factors, sigma(E) does not directly regulate the transcription of its own gene. Two promoters have been identified upstream of the sigE gene; one is regulated by the two-component system MprAB, while the other has been shown to be sigma(H) dependent. In this paper, we further characterize the regulation of sigma(E) by identifying its anti-sigma factor and a previously unknown promoter. Finally, we show that sigE can be translated from three different translational start codons, depending on the promoter used. Taken together, our data demonstrate that sigma(E) not only is subjected to complex transcriptional regulation but is also controlled at the translational and posttranslational levels.

SUBMITTER: Dona V

PROVIDER: S-EPMC2519537 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Evidence of complex transcriptional, translational, and posttranslational regulation of the extracytoplasmic function sigma factor sigmaE in Mycobacterium tuberculosis.

Donà Valentina V Rodrigue Sébastien S Dainese Elisa E Palù Giorgio G Gaudreau Luc L Manganelli Riccardo R Provvedi Roberta R

Journal of bacteriology 20080707 17

The extracytoplasmic factor (ECF) sigma factor sigma(E) is one of the most studied sigma factors of Mycobacterium tuberculosis. It has been shown to be involved in virulence as well as in survival under conditions of high temperature, alkaline pH, and exposure to detergents and oxidative stress. Unlike many ECF sigma factors, sigma(E) does not directly regulate the transcription of its own gene. Two promoters have been identified upstream of the sigE gene; one is regulated by the two-component s ...[more]

PMID: 18606740

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Project description:Extracytoplasmic function σ factors that are stress inducible are often sequestered in an inactive complex with a membrane-associated anti-σ factor. Mycobacterium tuberculosis membrane-associated anti-σ factors have a small, stable RNA gene A (ssrA)-like degron for targeted proteolysis. Interaction between the unfoldase, ClpX, and a substrate with an accessible degron initiates energy-dependent proteolysis. Four anti-σ factors with a mutation in the degron provided a set of natural substrates to evaluate the influence of the degron on degradation strength in ClpX-substrate processivity. We note that a point mutation in the degron (X-Ala-Ala) leads to an order-of-magnitude difference in the dwell time of the substrate on ClpX. Differences in ClpX/anti-σ interactions were correlated with changes in unfoldase activities. Green fluorescent protein (GFP) chimeras or polypeptides with a length identical to that of the anti-σ factor degron also demonstrate degron-dependent variation in ClpX activities. We show that degron-dependent ClpX activity leads to differences in anti-σ degradation, thereby regulating the release of free σ from the σ/anti-σ complex. M. tuberculosis ClpX activity thus influences changes in gene expression by modulating the cellular abundance of ECF σ factors.IMPORTANCE The ability of Mycobacterium tuberculosis to quickly adapt to changing environmental stimuli occurs by maintaining protein homeostasis. Extracytoplasmic function (ECF) σ factors play a significant role in coordinating the transcription profile to changes in environmental conditions. Release of the σ factor from the anti-σ is governed by the ClpXP2P1 assembly. M. tuberculosis ECF anti-σ factors have an ssrA-like degron for targeted degradation. A point mutation in the degron leads to differences in ClpX-mediated proteolysis and affects the cellular abundance of ECF σ factors. ClpX activity thus synchronizes changes in gene expression with environmental stimuli affecting M. tuberculosis physiology.

Project description:Salmonella enterica serovar Typhimurium (S. Typhimurium) elicits the starvation-stress response (SSR) due to starvation for an essential nutrient, e.g. a carbon/energy source (C-source). As part of the SSR, the alternative sigma factor sigma(E) is activated and induced. The authors suspect that this activation is, in part, triggered by changes in the S. Typhimurium cell envelope occurring during the adaptation from growth to carbon/energy starvation (C-starvation), and resulting in an increased need for sigma(E)-regulated factors involved in the proper folding and assembly of newly synthesized proteins destined for this extracytoplasmic compartment. This led to the hypothesis that a sigma(E) activation signal might arise during C-source shifts that cause the induction of proteins localized to the extracytoplasmic compartment, i.e. the outer membrane or periplasm, of the cell. To test this hypothesis, cultures were grown in minimal medium containing enough glucose to reach mid-exponential-phase, plus a non-limiting amount of a secondary 'less-preferred' but utilizable carbon/energy source. The sigma(E) activity was then monitored using plasmids carrying rpoEP1- and rpoEP2-lacZ transcriptional fusions, which exhibit sigma(E)-independent and -dependent lacZ expression, respectively. The secondary C-sources maltose, succinate and citrate, which have extracytoplasmic components involved in their utilization (e.g. LamB), resulted in a discernible diauxic lag period and a sustained increase in sigma(E) activity. Growth transition from glucose to other utilizable phosphotransferase (PTS) and non-PTS C-sources, such as trehalose, mannose, mannitol, fructose, glycerol, d-galactose or l-arabinose, did not cause a discernible diauxic lag period or a sustained increase in sigma(E) activity. Interestingly, a shift from glucose to melibiose, which does not use an extracytoplasmic-localized protein for uptake, did cause an observable diauxic lag period but did not result in a sustained increase in sigma(E) activity. In addition, overexpression of LamB from an arabinose-inducible promoter leads to a significant increase in sigma(E) activity in the absence of a glucose to maltose shift or C-starvation. Furthermore, a DeltalamB : : Omega-Km(r) mutant, lacking the LamB maltoporin, exhibited an approximately twofold reduction in the sustained sigma(E) activity observed during a glucose to maltose shift, again supporting the hypothesis. Interestingly, the LamB protein lacks the typical Y-X-F terminal tripeptide of the OmpC-like peptides that activate DegS protease activity leading to sigma(E) activation. It does, however, possess a terminal pentapeptide (Q-M-E-I-W-W) that may function as a ligand for a putative class II PDZ-binding site. The authors therefore propose that the sigma(E) regulon of S. Typhimurium not only is induced in response to deleterious environmental conditions, but also plays a role in the adaptation of cells to new growth conditions that necessitate changes in the extracytoplasmic compartment of the cell, which may involve alternative signal recognition and activation pathways that are independent of DegS.

Dataset Information

Evidence of complex transcriptional, translational, and posttranslational regulation of the extracytoplasmic function sigma factor sigmaE in Mycobacterium tuberculosis.

Publications

Evidence of complex transcriptional, translational, and posttranslational regulation of the extracytoplasmic function sigma factor sigmaE in Mycobacterium tuberculosis.

Similar Datasets

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