ResDE-Dependent Regulation of Enterotoxin Gene Expression in
            <i>Bacillus cereus</i>
            : Evidence for Multiple Modes of Binding for ResD and Interaction with Fnr

Esbelin, Julia; Armengaud, Jean; Zigha, Assia; Duport, Catherine

doi:10.1128/jb.00321-09

Cited by 32 publications

(44 citation statements)

References 37 publications

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“…47,48 Although the B. cereus FNR has an O 2 -responsive [4Fe-4S] cluster, the cluster does not appear to be important for DNA-binding at the nhe promoter (there is evidence for monomeric apo-FNR binding) or for interaction with the redoxresponsive regulator ResD (see below). [48][49][50] Oxygen-sensing by the Shigella FNR protein has been shown to play a role in coordinating the function of a Type III secretion system (T3SS) that is important for virulence. In the anaerobic lumen of the gastrointestinal tract, FNR primes the bacterium for invasion by activating expression of the T3SS needles, while repressing the expression of spa32 and spa33, which regulate the function of the T3SS.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

2014

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Molecular oxygen (O 2 ) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O 2 for their production. Furthermore, the ability to adapt to changes in O 2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O 2 and/or NO. Indirect sensors perceive the physiological effects of O 2 starvation. Thus, O 2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O 2 -and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis.

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Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

2014

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“…In B. cereus, the expression of most of the genes encoding metabolic enzymes is modulated by the two redox systems, ResDE (a two-component system) (6,24) and Fnr (a onecomponent system) (18,25), and the catabolite control protein A (CcpA) (26). Despite the knowledge currently gathered throughout these studies, we still lack a global quantitative understanding of the contribution of the multilevel regulatory events that govern metabolic modes (anaerobic fermentation versus aerobic respiration).…”

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confidence: 99%

Restricting Fermentative Potential by Proteome Remodeling

Clair¹,

Armengaud²,

Duport³

2012

Molecular & Cellular Proteomics

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Pathogenesis hinges on successful colonization of the gastrointestinal (GI) tract by pathogenic facultative anaerobes. The GI tract is a carbohydrate-limited environment with varying oxygen availability and oxidoreduction potential (ORP). How pathogenic bacteria are able to adapt and grow in these varying conditions remains a key fundamental question. Here, we designed a system biologyinspired approach to pinpoint the key regulators allowing Bacillus cereus to survive and grow efficiently under low ORP anoxic conditions mimicking those encountered in the intestinal lumen. We assessed the proteome components using high throughput nanoLC-MS/MS techniques, reconstituted the main metabolic circuits, constructed ⌬ohrA and ⌬ohrR mutants, and analyzed the impacts of ohrA and ohrR disruptions by a novel round of shotgun proteomics. Our study revealed that OhrR and OhrA are crucial to the successful adaptation of B. cereus to the GI tract environment. Specifically, we showed that B. cereus restricts its fermentative growth under low ORP anaerobiosis and sustains efficient aerobic respiratory metabolism, motility, and stress response via OhrRA-dependent proteome remodeling. Finally, our results introduced a new adaptive strategy where facultative anaerobes prefer to restrict their fermentative potential for a long term benefit. Molecular & Cellular Proteomics 11: 10.1074/ mcp.M111.013102, 1-13, 2012.Facultative anaerobes encompass all the major pathogens of the human gastrointestinal (GI) 1 tract. The GI tract poses several challenges for pathogens because it is sliced into distinct niches with different oxygen concentrations and different oxidoreduction potentials (ORP) (1-3). Although much is known about gene expression and metabolism under fully aerobic and high ORP anaerobic condition (4, 5), our knowledge about the physiological impact of low ORP anoxic conditions and the underlying molecular mechanisms is scarce (6).Bacillus cereus is a notorious food-borne pathogenic bacterium. Like the closely related Bacillus anthracis (7,8), it is a recognized agent of GI tract infections (9 -11). The critical step of infection takes place in the small intestine, where B. cereus has to grow and produce virulence factors to induce diarrheal disease (11, 12). Thus, how B. cereus adapts its catabolism and regulates its proteome across the range of physiologically relevant ORP and oxygen availabilities is important for its survival and growth. In B. cereus, anaerobic and aerobic catabolism work through different pathways. In the presence of oxygen, reducing equivalents generated by glycolysis and the TCA cycle (NADH and FADH) are reoxidized by the respiratory chain, resulting in the buildup of a proton motive force and the subsequent synthesis of ATP. Acetate excretion can occur aerobically when carbon flux into the cells exceeds TCA cycle capacity. In the absence of oxygen or other external electron acceptors (such as nitrate), NADH is reoxidized in terminal step fermentative reactions from pyruvate. When grown in pH-controlled ana...

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“…The human intestinal environment is pH-regulated, oxygen-deprived (26, 27), highly reduced (ORP ϳ Ϫ150mV) (28), and carbohydrate-limited (29,30). To grow in such conditions, B. cereus may need to adapt its fermentative metabolism and express virulence factors through signal transduction pathways involving the two-component ResDE system (31,32) and the redox regulator Fnr (33)(34)(35).…”

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confidence: 99%

Expanding the Known Repertoire of Virulence Factors Produced by Bacillus cereus through Early Secretome Profiling in Three Redox Conditions

Clair

Roussi

Armengaud

et al. 2010

Molecular & Cellular Proteomics

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141

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The pathogen Bacillus cereus causes diarrheal disease in humans. In the small intestine, B. cereus has to deal with anaerobiosis, low oxidoreduction potential, and carbohydrate limitation conditions. To gain insight into the virulence potential of low density B. cereus cells in such an environment, we cultured bacteria in low and high oxidoreduction potential anoxic conditions and in fully oxic conditions and compared their full secretomes. A unique pattern of proteins assigned to virulence factors was revealed. Among the 57 virulence-related factors, 31 were found for the first time in the B. cereus secretome. The putative fourth component of hemolysin BL (HblB), enterotoxin FM, hemolysin II, and three new putative conserved enterotoxins were uncovered. Cross-comparison of the relative abundance of secreted proteins reveals that a restricted set comprising 19 proteins showed significant changes in response to redox condition changes. We complemented these results with transcriptomics data and confirmed the cytotoxicity of the B. cereus secretome toward Caco-2 human epithelial cells. Our data suggest that (i) the redox-dependent regulatory pathway may modulate the expression of a subset of virulence factors to ensure an appropriate response in a specific redox environment, and (ii) an early growth phase-dependent pathway could regulate the expression of several virulence factors, allowing B. cereus to infect a host whatever the redox conditions. This early growth phase-dependent pathway may function, at least partially, independently of the pleiotropic virulence gene regulator PlcR and may therefore be more specific to the B. cereus group.

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ResDE-Dependent Regulation of Enterotoxin Gene Expression in Bacillus cereus : Evidence for Multiple Modes of Binding for ResD and Interaction with Fnr

Abstract: In the food-borne pathogen

Cited by 32 publications

References 37 publications

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

Restricting Fermentative Potential by Proteome Remodeling

Expanding the Known Repertoire of Virulence Factors Produced by Bacillus cereus through Early Secretome Profiling in Three Redox Conditions

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