Contributions of Individual B-Dependent General Stress Genes to Oxidative Stress Resistance of Bacillus subtilis

Ernst-Moritz-Arndt Universität Institut für Mikrobiologie, Greifswald, Germany.
Journal of bacteriology (Impact Factor: 2.81). 05/2012; 194(14):3601-10. DOI: 10.1128/JB.00528-12
Source: PubMed


The general stress regulon of Bacillus subtilis comprises approximately 200 genes and is under the control of the alternative sigma factor σB. The activation of σB occurs in response to multiple physical stress stimuli as well as energy starvation conditions. The expression of the general
stress proteins provides growing and stationary nonsporulating vegetative cells with nonspecific and broad stress resistance.
A previous comprehensive phenotype screening analysis of 94 general stress gene mutants in response to severe growth-inhibiting
stress stimuli, including ethanol, NaCl, heat, and cold, indicated that secondary oxidative stress may be a common component
of severe physical stress. Here we tested the individual contributions of the same set of 94 mutants to the development of
resistance against exposure to the superoxide-generating agent paraquat and hydrogen peroxide (H2O2). In fact, 62 mutants displayed significantly decreased survival rates in response to paraquat and/or H2O2 stress compared to the wild type at a confidence level of an α value of ≤0.01. Thus, we were able to assign 47 general stress
genes to survival against superoxide, 6 genes to protection from H2O2 stress, and 9 genes to the survival against both. Furthermore, we show that a considerable overlap exists between the phenotype
clusters previously assumed to be involved in oxidative stress management and the actual group of oxidative-stress-sensitive
mutants. Our data provide information that many general stress proteins with still unknown functions are implicated in oxidative
stress resistance and further support the notion that different severe physical stress stimuli elicit a common secondary oxidative

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    • "n important protein in correct functioning of the ribosomes ( Akanuma et al . , 2012 ) but the effect of knocking - out rpsU in B . subtilis on its stress resistance was not evaluated . Deletion of the genes encoding ribosomal pro - teins L31 and L25 in B . subtilis did result in phenotypes with increased stress resistance ( Höper et al . , 2005 ; Reder et al . , 2012 ) . Some recent proteome and transcriptome studies in L . monocy - togenes found differential expression of ribosomal proteins upon stress exposure ( Ivy et al . , 2012 ; Durack et al . , 2013 ; Melo et al . , 2013 ; Pleitner et al . , 2014 ) . Also , a role in cold adaptation and cold stress response of L . monocytogenes has been sugge"
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    ABSTRACT: The dynamic response of microorganisms to environmental conditions depends on the behavior of individual cells within the population. Adverse environments can select for stable stress resistant subpopulations. In this study, we aimed to get more insight in the diversity within Listeria monocytogenes LO28 populations, and the genetic basis for the increased resistance of stable resistant fractions isolated after acid exposure. Phenotypic cluster analysis of 23 variants resulted in three clusters and four individual variants and revealed multiple-stress resistance, with both unique and overlapping features related to stress resistance, growth, motility, biofilm formation and virulence indicators. A higher glutamate decarboxylase (GAD) activity correlated with increased acid resistance. Whole genome sequencing revealed mutations in rpsU, encoding ribosomal protein S21 in the largest phenotypic cluster, while mutations in ctsR, which were previously shown to be responsible for increased resistance of heat and high hydrostatic pressure (HHP) resistant variants, were not found in the acid resistant variants. This underlined that large population diversity exists within one L. monocytogenes strain and that different adverse conditions drive selection for different variants. The finding that acid stress selects for rpsU variants provides potential insights in the mechanisms underlying population diversity of L. monocytogenes.
    Full-text · Article · May 2015 · Frontiers in Microbiology
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    • "In B. subtilis a secondary oxidative stress response is linked to the MgsR transcriptional regulator [87,88]. This σB dependent regulator seems to sense and integrate the secondary oxidative stress signal and controls a specific subregulon within the σB dependent general stress regulon. "
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    ABSTRACT: The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.
    Full-text · Article · Nov 2013 · PLoS ONE
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    • "This hypothesis is supported by the results of a recent follow-up phenotype screening of the previously used set of 94 general stress gene mutants upon treatment with the superoxide-generating agent paraquat and hydrogen peroxide. In this study, 62 mutants (66%) displayed significantly decreased survival rates in response to oxidative stress (Reder et al., 2012). "
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    ABSTRACT: The alternative sigma factor σ(B) is the master regulator of the general stress regulon that comprises approximately 200 genes whose products confer a comprehensive stress resistance to Bacillus subtilis. The characterization of MgsR (modulator of the general stress response) revealed that the activation and induction of σ(B) are a prerequisite but not sufficient for a full expression of all general stress genes. MgsR is a paralogue of the global regulator of the diamide stress response, Spx, and controls a subregulon of the general stress response. Here we demonstrate that MgsR activity is controlled at multiple levels. These mechanisms include a positive autoregulatory loop on mgsR transcription, a post-translational redox-sensitive activation step by an intramolecular disulfide bond formation in response to ethanol stress in vivo, as well as rapid proteolytic degradation of MgsR by the ClpXP and ClpCP proteases. Our results indicate an elaborate regulatory network integrating secondary oxidative stress signals into a σ(B) -mediated regulatory cascade that is aimed at rapid and finely tuned target gene expression to coordinately fulfil the physiological needs of the cell in the face of multiple environmental changes.
    Full-text · Article · Jul 2012 · Environmental Microbiology
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