Clostridial Gas Gangrene. II. Phospholipase C–Induced Activation of Platelet gpIIbIIIa Mediates Vascular Occlusion and Myonecrosis in<i>Clostridium perfringens</i>Gas Gangrene

Bryant, Amy E.; Chen, Richard Y. Z.; Nagata, Y.; Wang, Y.; Lee, C. H.; Finegold, Sydney M.; Guth, Paul H.; Stevens, Dennis L.

doi:10.1086/315757

Cited by 102 publications

(97 citation statements)

References 30 publications

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“…However, cell lysis may not be the major biological effect of PFO in an infected tissue. It is well established that both CPA and PFO are responsible for the characteristic lack of a leukocyte influx at the focus of a C. perfringens-mediated myonecrotic infection (46)(47)(48), and, like other CDCs, PFO is a Toll-like receptor 4 (TLR4) agonist that induces tumor necrosis factor alpha (TNF-␣) and IL-6 expression and apoptosis in cultured macrophages by activating the p38 MAPK pathway (49).…”

Section: Chromosomally Encoded Toxinsmentioning

confidence: 99%

Toxin Plasmids of Clostridium perfringens

Adams

Bannam

et al. 2013

Microbiol Mol Biol Rev

231

282

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SUMMARY In both humans and animals, Clostridium perfringens is an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced by C. perfringens are encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. A C. perfringens strain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins when C. perfringens disease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids of C. perfringens share an ∼35-kb region containing a Tn 916 -related conjugation locus named tcp (transfer of clostridial plasmids). This tcp locus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain to C. perfringens normal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely provides C. perfringens with considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract.

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Section: Chromosomally Encoded Toxinsmentioning

confidence: 99%

Toxin Plasmids of Clostridium perfringens

Adams

Bannam

et al. 2013

Microbiol Mol Biol Rev

231

282

View full text Add to dashboard Cite

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“…In endothelial cells, alpha-toxin stimulates prostacyclin and PAF production, which likely contributes to increased vascular permeability and neutrophil adhesion to endothelial cells (227). In platelets, alpha-toxin causes fibrinogen receptor gpIIbIIIa translocation to the membrane and triggers a conformational change in the surface-expressed receptors, inducing aggregation and leading to vascular occlusion (228,229). Thus, alpha-toxin activates transduction pathways in neutrophils, endothelial cells,…”

Section: Phospholipase Csmentioning

confidence: 99%

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

Flores-Dı́az

Monturiol-Gross

Naylor

et al. 2016

Microbiol Mol Biol Rev

173

143

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SUMMARYBacterial sphingomyelinases and phospholipases are a heterogeneous group of esterases which are usually surface associated or secreted by a wide variety of Gram-positive and Gram-negative bacteria. These enzymes hydrolyze sphingomyelin and glycerophospholipids, respectively, generating products identical to the ones produced by eukaryotic enzymes which play crucial roles in distinct physiological processes, including membrane dynamics, cellular signaling, migration, growth, and death. Several bacterial sphingomyelinases and phospholipases are essential for virulence of extracellular, facultative, or obligate intracellular pathogens, as these enzymes contribute to phagosomal escape or phagosomal maturation avoidance, favoring tissue colonization, infection establishment and progression, or immune response evasion. This work presents a classification proposal for bacterial sphingomyelinases and phospholipases that considers not only their enzymatic activities but also their structural aspects. An overview of the main physiopathological activities is provided for each enzyme type, as are examples in which inactivation of a sphingomyelinase- or a phospholipase-encoding gene impairs the virulence of a pathogen. The identification of sphingomyelinases and phospholipases important for bacterial pathogenesis and the development of inhibitors for these enzymes could generate candidate vaccines and therapeutic agents, which will diminish the impacts of the associated human and animal diseases.

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“…Η απορρύθμιση των ICAM-1 (intercellular adhesion molecular-1) και ELAM-1 (endothelial leukocyte adhesion molecule-1) στην επιφάνεια των ενδοθηλιακών κυττάρων, σε συνδυασμό με την αυξη μένη παραγωγή IL-8, η οποία δρα χημειοτακτικά για τα ουδετερόφιλα, έχει ως αποτέλεσμα την έμφραξη των αιμοφόρων αγγείων, παρεμποδίζοντας τη μετα νάστευση των ουδετερόφιλων κυττάρων (Bryant and Stevens 1996, Bunting et al 1997. Επίσης, η τοξίνη -α θα μπορονοε να οδηγήσει και σε συγκόλληση των αιμοπεταλίων, με συνέπεια την αγγειακή απόφραξη (Bryant et al 2000).…”

Section: τοξίνη -αunclassified

Update on the toxins of Clostridium perfringens and their actions

Tsiouris

Georgopoulou

Petridou

2017

J Hellenic Vet Med Soc

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Clostridia appeared as a distinct class, approximately 2.7 billion years ago, before the initial formation of oxygen. Clostridium perfringens is widely distributed throughout the environment due to its ability to form spores. Furthermore, it is a member of intestinal microbiota in animals and human. In 2002, the complete genome of C perfringens strain 13 was published. Genomic analysis has revealed that C. perfringens lacks the genetic machinery to produce 13 essential amino acids and it obtains these in vivo via the action of its toxins. Toxins of C perfringens can be divided into major, minor and enterotoxin. C perfringens strains are classified into five toxinotypes (A, B, C, D and E), based on the production of four major toxins. Alpha toxin is the best and most studied major toxin of C perfringens and it was the first bacterial toxin established to possess enzymatic activity. It has haemolytic, necrotic and cytolytic activity, it can lyse platelets and leukocytes and it can damage fibroblasts and muscle cell membranes. Expression of epa gene, which is responsible for the production of alpha toxin by C perfringens, is down-regulated in the normal healthy gut, but it is upregulated to initiate enteric disease in response to an environmental signal. C perfringens appears to be regulated in a quorum sensing manner, using oligopeptides, AI-2 or both, to regulate expression of the epa gene, and thus the synthesis of alpha toxin. Beta toxin is recognized as an important agent in necrotic enteritis of humans and it is the second most lethal C. perfringens toxin following epsilon toxin. Beta toxin is a membrane spanning protein that oligomerizes to form channels in susceptible cells or it primarily acts as a neurotoxin. Epsilon toxin is the most potent of the C. perfringens toxins and the third most potent neurotoxin from the Clostridium spp., following botulinum and tetanus toxins. Epsilon toxin of C perfringens type D causes enterotoxaemia and pulpy kidneys disease of lambs. Iota toxin causes disruption of the actin cytoskeleton and cell barrier integrity and it is the less toxic of the major toxins of C perfringens. Although C perfringens enterotoxin is not classified as one of the major toxins of C perfringens, it is the third most common cause of food poisoning in industrialized nations. It is not secreted by the cells of growing bacteria, but it is released only with the sporulation of C perfringens. Not all strains of C perfringens carry the epe gene, which is responsible for the production of enterotoxin. Theta toxin is a pore-forming cytolysin that can lyse red blood cells. It is produced by all types of C perfringens. Together with alpha-toxin, theta-toxin modulates the host inflammatory response. ß2 toxin is a pore forming toxin which is involved in necrotic enteritis of swine and horse, in haemorragic enteritis of bovine in diarrhea cases of dogs and along with enterotoxin in diarrhea cases of humans. Recently, -NetB, a novel toxin that is associated with broiler necrotic enteritis, has been described. The mechanism of its action seems to involve the formation of small hydrophilic pores. Other toxins of C. perfringens include λ-toxin, ô-toxin, μ-toxin, v-toxin, κ-toxin, a-clostripain like protease and neuraminidase/sialidase. These toxins can act as enzymes, while many of them can act synergically or supplementally with major pore forming toxins. Potentially, C. perfringens might produce more toxins, which have not been identified. Finally, the actions of C. perfringens toxins, major or minor, in some diseases have not been figured out.

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Clostridial Gas Gangrene. II. Phospholipase C–Induced Activation of Platelet gpIIbIIIa Mediates Vascular Occlusion and Myonecrosis inClostridium perfringensGas Gangrene

Cited by 102 publications

References 30 publications

Toxin Plasmids of Clostridium perfringens

Toxin Plasmids of Clostridium perfringens

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

Update on the toxins of Clostridium perfringens and their actions

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