Mycobacterium tuberculosis sigF is part of a gene cluster with similarities to the Bacillus subtilis sigF and sigB operons

DeMaio, James; Zhang, Y.; Ko, Chung‐Wang; Bishai, William R.

doi:10.1016/s0962-8479(97)90010-1

Cited by 73 publications

(88 citation statements)

References 33 publications

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“…Two mycobacterial sigma factors have been implicated in stationary-phase gene regulation : sigF (Demaio et al, 1996(Demaio et al, , 1997Michele et al, 1999) and sigB (Beggs et al, 1996 ;Doukhan et al, 1995 ;Hu & Coates, 1999a ;Predich et al, 1995). Both sigma factors are up-regulated during O # -limited stationary phase (Hu & Coates, 1999a), which is an in vitro model for mycobacterial persistence developed by Wayne and co-workers (Wayne, 1994 ;Wayne & Hayes, 1996).…”

Section: Introductionmentioning

confidence: 99%

Mutants of Mycobacterium smegmatis impaired in stationary-phase survival The GenBank accession numbers for the sequences determined in this work are: AJ277088 (mutant 272A), AJ277089 (mutant 272E), AJ27790 (mutant 317C), AJ277152 (mutant 492A) and AJ276883 (mutant 3910D).

et al. 2000

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A bank of 600 insertional mutants of Mycobacterium smegmatis was screened for mutants defective in stationary-phase survival. Of 74 mutants picked by the initial screen, 21 had stationary-phase survival defects and 7 of these were studied in more detail. In general, mutants survived stationary phase significantly less well in rich medium than under carbon-starvation conditions. In all cases the loss of viability in stationary phase was not complete even after prolonged incubation. All mutants showed an initial decrease in viability, during the first 40 d in stationary phase, followed by an increase in viable counts that returned viability close to the levels of the wild-type. Southern hybridization experiments showed that recovery of viability was not a consequence of precise excision or movement of the transposon. Two of the survival mutants differed from the wild-type in their colony morphology, and recovery of their viability in stationary phase was coincident with the return of wild-type colony morphology. It is possible that second-site suppressor mutations accumulate that alleviate the effects of the original mutation. For five of the mutants the DNA flanking the site of transposition was amplified by ligation-mediated PCR and sequenced to identify the disrupted locus. In each case, homologous genes were identified in the Mycobacterium tuberculosis genome, three of which have clearly predicted functions in M. tuberculosis as a penicillin-binding protein, in biotin biosynthesis and as a polyketide synthase. This is the first identification of genes implicated in the stationary-phase survival of mycobacteria.

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Section: Introductionmentioning

confidence: 99%

Mutants of Mycobacterium smegmatis impaired in stationary-phase survival The GenBank accession numbers for the sequences determined in this work are: AJ277088 (mutant 272A), AJ277089 (mutant 272E), AJ27790 (mutant 317C), AJ277152 (mutant 492A) and AJ276883 (mutant 3910D).

et al. 2000

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“…In these systems, the phosphorylation state of sigma factor regulators results from the balance of dedicated kinases and phosphatases that are typically encoded in the same operon as the sigma factor. A similar system may operate in mycobacteria in regulating the general stress response sigma factor SigF, however the components of this system have not been fully defined (27,28). In contrast to the B. subtilis paradigm, SigH and PknB are independently regulated, and PknB has an essential role in regulating cell shape and cell wall synthesis that is distinct from the stress response transcription regulation mediated by SigH (11,12).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis

Park

Kang

Husson

2008

Proc. Natl. Acad. Sci. U.S.A.

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SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in Mycobacterium tuberculosis, and this sigma factor is required for virulence in animal models of infection. SigH is negatively regulated by RshA, its cognate anti-sigma factor, which functions as a stress sensor and redox switch. While RshA provides a direct mechanism for sensing stress and activating transcription, bacteria use several types of signal transduction systems to sense the external environment. M. tuberculosis encodes several serine-threonine protein kinase signaling molecules, 2 of which, PknA and PknB, are essential and have been shown to regulate cell morphology and cell wall synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated in vitro and in vivo by PknB. We show that phosphorylation of RshA, but not SigH, interferes with the interaction of these 2 proteins in vitro. Consistent with this finding, negative regulation of SigH activity by RshA in vivo is partially relieved in strains in which pknB is over-expressed, resulting in increased resistance to oxidative stress. These findings demonstrate an interaction between the signaling pathways mediated by PknB and the stress response regulon controlled by SigH. The intersection of these apparently discrete regulatory systems provides a mechanism by which limited activation of the SigH-dependent stress response in M. tuberculosis can be achieved. Coordination of the PknB and SigH regulatory pathways through phosphorylation of RshA may lead to adaptive responses that are important in the pathogenesis of M. tuberculosis infection.anti-sigma factor ͉ sigma factor ͉ transcription regulation ͉ phosphorylation S igH, an alternative sigma factor of Mycobacterium tuberculosis and other mycobacterial species, is a central regulator of the response to oxidative, nitrosative, and heat stresses. SigH directly regulates both effectors of the response to these stresses and additional transcription regulators that control expression of a broad range of stress response genes (1-4). The SigHdependent activation of this extensive stress response regulon is critical for M. tuberculosis virulence, as a sigH mutant is highly attenuated in the mouse model of infection (5).SigH activity is regulated at the transcriptional level via autoregulation of the sigH promoter, and posttranslationally via interaction with its cognate anti-sigma factor, RshA. This protein is a member of the Zinc-associated anti-sigma (ZAS) family, several members of which, including RshA, have been shown to function as redox switch proteins (3, 6-8). The interaction of RshA with SigH is disrupted under oxidizing conditions, allowing SigH to associate with core RNA polymerase and activate transcription of stress response genes and additional transcription regulators. The autoregulation of the sigH promoter results in rapid, strong induction of the SigH regulon following oxidative stress, which is maintained until redox homeostasis is reestablished and th...

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“…SigF) related to the sporulation cascade in other bacteria, under stressful conditions [17][18][19] Dormant "noncultureable" bacilli can be "resuscitated" with phospholipids and a specific factor (Rpf) synthesised by growing bacilli [20][21][22][23][24] Experiments in animal models…”

Section: Experiments In Vitromentioning

confidence: 99%

“…The study of both the genomic and the proteomic expression of M. tuberculosis under stress conditions, such as acidity, low oxygen pressure, heat, cold, hydroxide peroxide, or even stationary growth phase, showed an increase in the expression of the RNA polymerase sigma (Sig)F unit, which was also related to the accumulation of an a-crystalline-like 16-kDa protein in the cell wall [17]. Interestingly, the presence of SigF during exponential growth was deleterious for M. bovis bacilli Calmette-Guérin (BCG) [18], perhaps because it directed the transcription of genes required for the stationary phase or a spore-like state when exponential growth was required. Whether the M. tuberculosis SigF protein primarily regulates a sporulation-like cascade (the same as Bacillus subtilis SigF and Streptomyces coelicolor SigF) is unknown [19].…”

Section: Experiments In Vitromentioning

confidence: 99%

On the nature ofMycobacterium tuberculosis-latent bacilli

Cardona¹

2004

Eur Respir J

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On the nature of Mycobacterium tuberculosis-latent bacilli. P-J. Cardona, J. Ruiz-Manzano. #ERS Journals Ltd 2004. ABSTRACT: Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to stressful conditions generated by the infected host against them. By slowing metabolism or becoming dormant, they may counterbalance these conditions and appear as silent to the immune system. Moreover, the dynamic turnover of the infected cells provokes a constant reactivation of the latent bacilli when the environmental conditions are favourable, or an activation after being dormant in necrotic and fibrotic lesions for a long period of time. Since there is no in vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the current authors strongly favour the possibility that latent tuberculosis infection can be maintained for no longer than y10 yrs, which is, nowadays, a time period very close to that considered for "primary" tuberculosis. This concept may also be helpful for newer epidemiological considerations regarding the real impact of reinfection in tuberculosis.

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Mycobacterium tuberculosis sigF is part of a gene cluster with similarities to the Bacillus subtilis sigF and sigB operons

Cited by 73 publications

References 33 publications

Mutants of Mycobacterium smegmatis impaired in stationary-phase survival The GenBank accession numbers for the sequences determined in this work are: AJ277088 (mutant 272A), AJ277089 (mutant 272E), AJ27790 (mutant 317C), AJ277152 (mutant 492A) and AJ276883 (mutant 3910D).

Mutants of Mycobacterium smegmatis impaired in stationary-phase survival The GenBank accession numbers for the sequences determined in this work are: AJ277088 (mutant 272A), AJ277089 (mutant 272E), AJ27790 (mutant 317C), AJ277152 (mutant 492A) and AJ276883 (mutant 3910D).

Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis

On the nature ofMycobacterium tuberculosis-latent bacilli

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