Diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes

Fimlaid, Kelly A.; Shen, Aimee

doi:10.1016/j.mib.2015.01.006

Cited by 125 publications

(116 citation statements)

References 63 publications

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“…Studies have provided insight into the workings of the pathogen and highlighted aspects of its biology that differ from the situation in other studied bacteria. For instance, the order, activation and function of sporulation sigma factors of C. difficile deviate from what is known for the best-studied Gram-positive spore former, Bacillus subtilis 225 . Perhaps this difference should not come as a surprise, as the last common ancestor of bacilli and clostridia dates back ~2.7 billion years, only shortly after the divergence of Gram-positive and Gram-negative bacteria (3.2 billion years ago) 226 .…”

Section: Discussionmentioning

confidence: 81%

Clostridium difficile infection

Smits

Lyras

Lacy

et al. 2016

Nat Rev Dis Primers

653

674

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Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis — the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.

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Section: Discussionmentioning

confidence: 81%

Clostridium difficile infection

Smits

Lyras

Lacy

et al. 2016

Nat Rev Dis Primers

653

674

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“…C. perfringens is a spore-forming bacterium, and sporulation is highly regulated by various regulatory factors and proteins (36,37). The Spo0A protein is a primary regulatory protein of sporulation.…”

Section: Resultsmentioning

confidence: 99%

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

et al. 2017

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Recently, many Gram-positive bacteria as well as Gram-negative bacteria have been reported to produce membrane vesicles (MVs), but little is known regarding the regulators involved in MV formation. We found that a Gram-positive anaerobic pathogen, Clostridium perfringens, produces MVs predominantly containing membrane proteins and cell wall components. These MVs stimulated proinflammatory cytokine production in mouse macrophage-like cells. We suggested that MVs induced interleukin-6 production through the Toll-like receptor 2 (TLR2) signaling pathway. Thus, the MV could have a role in the bacterium-host interaction and bacterial infection pathogenesis. Moreover, we found that the sporulation master regulator gene spo0A was required for vesiculogenesis. A conserved, phosphorylated aspartate residue of Spo0A was indispensable for MV production, suggesting that the phosphorylation of Spo0A triggers MV production. Multiple orphan sensor kinases necessary for sporulation were also required to maximize MV production. These findings imply that C. perfringens actively produces immunoactive MVs in response to the environment changing, as recognized by membrane-spanning sensor kinases and by modulating the phosphorylation level of Spo0A.

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“…Partner-switching systems are one among other mechanisms by which bacteria connect cue transmission and gene expression (27)(28)(29). The partner-switching system that regulates B consists of an antisigma factor with a kinase activity (RsbW), two phosphatases (RsbU and RsbP), and an anti-sigma antagonist (RsbV) that contains a phosphorylatable serine residue in its sequence.…”

mentioning

confidence: 99%

The General Stress Response σS Is Regulated by a Partner Switch in the Gram-negative Bacterium Shewanella oneidensis

Bouillet¹,

Genest²,

Jourlin-Castelli³

et al. 2016

Journal of Biological Chemistry

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Edited by Thomas SöllnerHere, we show that a partner-switching system of the aquatic Proteobacterium Shewanella oneidensis regulates post-translationally S (also called RpoS), the general stress response sigma factor. Genes SO2118 and SO2119 encode CrsA and CrsR, respectively. CrsR is a three-domain protein comprising a receiver, a phosphatase, and a kinase/anti-sigma domains, and CrsA is an anti-sigma antagonist. In vitro, CrsR sequesters S and possesses kinase and phosphatase activities toward CrsA. In turn, dephosphorylated CrsA binds the anti-sigma domain of CrsR to allow the release of S . This study reveals a novel pathway that post-translationally regulates the general stress response sigma factor differently than what was described for other proteobacteria like Escherichia coli. We argue that this pathway allows probably a rapid bacterial adaptation.

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Diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes

Cited by 125 publications

References 63 publications

Clostridium difficile infection

Clostridium difficile infection

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

The General Stress Response σS Is Regulated by a Partner Switch in the Gram-negative Bacterium Shewanella oneidensis

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