SigF Controls Carotenoid Pigment Production and Affects Transformation Efficiency and Hydrogen Peroxide Sensitivity in
            <i>Mycobacterium smegmatis</i>

Provvedi, Roberta; Kocı́ncová, Dana; Donà, Valentina; Euphrasie, Daniel; Daffé, Mamadou; Etienne, Gilles; Manganelli, Riccardo; Reyrat, Jean‐Marc

doi:10.1128/jb.00714-08

Cited by 42 publications

(62 citation statements)

References 30 publications

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“…In M. smegmatis, loss of sigF increases susceptibility to oxidative stress, acidic pH, and heat shock (12) and disables the synthesis of protective carotenoids (28). This suggests that SigF mediates a general stress response.…”

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confidence: 99%

The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress

et al. 2010

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SigF is an alternative sigma factor that is highly conserved among species of the genus Mycobacterium. In this study we identified the SigF regulon in Mycobacterium smegmatis using whole-genome microarray and promoter consensus analyses. In total, 64 genes in exponential phase and 124 genes in stationary phase are SigF dependent (P < 0.01, >2-fold expression change). Our experimental data reveal the SigF-dependent promoter consensus GTTT-N (15-17) -GGGTA for M. smegmatis, and we propose 130 potential genes under direct control of SigF, of which more than 50% exhibited reduced expression in a ⌬sigF strain. We previously reported an increased susceptibility of the ⌬sigF strain to heat and oxidative stress, and our expression data indicate a molecular basis for these phenotypes. We observed SigF-dependent expression of several genes purportedly involved in oxidative stress defense, namely, a heme-containing catalase, a manganese-containing catalase, a superoxide dismutase, the starvation-induced DNA-protecting protein MsDps1, and the biosynthesis genes for the carotenoid isorenieratene. Our data suggest that SigF regulates the biosynthesis of the thermoprotectant trehalose, as well as an uptake system for osmoregulatory compounds, and this may explain the increased heat susceptibility of the ⌬sigF strain. We identified the regulatory proteins SigH3, PhoP, WhiB1, and WhiB4 as possible genes under direct control of SigF and propose four novel anti-sigma factor antagonists that could be involved in the posttranslational regulation of SigF in M. smegmatis. This study emphasizes the importance of this sigma factor for stationary-phase adaptation and stress response in mycobacteria.The success of Mycobacterium tuberculosis as a pathogen can be attributed to its capacity to adapt to environmental changes throughout the course of infection. These changes include nutrient deprivation, hypoxia, various exogenous stress conditions, and the intraphagosomal environment. A large cohort of genes that facilitate this adaptation has been identified, and among them are many genes for transcriptional regulators such as sigma factors that modulate gene expression in response to different physiological cues. Sigma factors interact with the RNA polymerase to allow binding to specific promoter sequences and initiation of gene transcription. Mycobacteria harbor sigma factors of only the 70 family, which fall into four different categories. SigA (group 1) is the essential primary sigma factor in mycobacteria, and SigB (group 2) is its nonessential paralog. SigF (group 3) and extracytoplasmic function (ECF) sigma factors (group 4) are alternative sigma factors, which allow adaptation to a wide range of internal and external stimuli. Alternative sigma factors vary considerably in type and numbers between species, mirroring their different requirements for stress response (15).Thirteen sigma factors have been identified in M. tuberculosis (23,29). Eleven of these are classified as alternative sigma factors, and many of them are recognized as ...

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confidence: 99%

The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress

et al. 2010

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“…Likely the presence or absence of carotenoid compounds dictates resistance to oxidative stress. In addition, lack of sigF increases transformation efficiency indicating the cell envelope has become potentially more porous [24]. Possibly carotenoid compounds lead to stabilization of the cell envelope, as well as making this structure less traversable.…”

Section: Mycobacterial Diseasesmentioning

confidence: 99%

“…Pre-priming via environmental acidity to induce carotenoid compound induction may increase resistance to acidity in vivo, as well as resistance to oxidative stress. In fact, recently when carotenoid production was inhibited in M. smegmatis by a sigF disruption, it did increase sensitivity of these mycobacteria to oxidative stress [24,26]. Carotenoids are well known to detoxify oxidative stress due to their double bonds [1].…”

Section: Mycobacterial Diseasesmentioning

confidence: 99%

“…In addition, at least for M. smegmatis, pigment production is thought to be controlled by the sigma factor SigF [24,25]. In M. smegmatis a deletion in the sigF gene resulted in a bacterium which not only cannot produce pigments, but a mutant mycobacterium sensitive to oxidative stress as well [24,26]. Likely the presence or absence of carotenoid compounds dictates resistance to oxidative stress.…”

Section: Mycobacterial Diseasesmentioning

confidence: 99%

“…In M. smegmatis, exposure to acidity transcriptionally upregulates the homologue of this promoter region [17]. In addition, at least for M. smegmatis, pigment production is thought to be controlled by the sigma factor SigF [24,25]. In M. smegmatis a deletion in the sigF gene resulted in a bacterium which not only cannot produce pigments, but a mutant mycobacterium sensitive to oxidative stress as well [24,26].…”

Section: Mycobacterial Diseasesmentioning

confidence: 99%

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Saviola¹

2014

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In recent years pigments have been identified in human nutrition to have a positive effect on human health and reduction to oxidative stress exposure. In the media it has become common wisdom that colourful food is naturally better to consume for humans and animals. Now recently it has been shown that pigments aid microbial species as well, and conversely these microbial pigments may result in more morbidity and mortality for the human host infected by these colourful microbes. Similar pigments that are available for consumption in food are also present in many bacterial species. Presumably these pigments aid the bacteria in their survival in the environment and within a human or animal host. Importantly, interference with the production of certain microbial pigments results in some bacterial strains that are more susceptible to environmental stressors and the host immune system. These studies seem to indicate a role of pigments for in vivo survival by microbial species.

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The α1β1 region is crucial for biofilm enhancement activity of MTC28 in Mycobacterium smegmatis

2017

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We show here that MTC28, a secretory antigen of 28 kDa from Mycobacterium tuberculosis, is involved in biofilm formation. The exogenous addition of MTC28 to the culture medium as well its expression in Mycobacterium smegmatis mc 155 shows an enhancement in biofilm formation, which leads to drug resistance. Structural analysis of MTC28 followed by mutational studies confirms the role of its α1β1 region in the biofilm enhancement activity. Confocal and flow cytometry studies show that the α1β1 region of MTC28 is crucial for binding to the M. smegmatis cell wall. The enhancement in biofilm formation due to MTC28 is also observed in M. tuberculosis H37Ra. This is the first report on the structure-function relationship of MTC28.

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SigF Controls Carotenoid Pigment Production and Affects Transformation Efficiency and Hydrogen Peroxide Sensitivity in Mycobacterium smegmatis

Cited by 42 publications

References 30 publications

The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress

The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress

Pigments and Pathogenesis

The α1β1 region is crucial for biofilm enhancement activity of MTC28 in Mycobacterium smegmatis

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