Bio: Robert Bayles is an academic researcher from University of Oklahoma Health Sciences Center. The author has contributed to research in topics: Clostridium perfringens beta toxin & Toxoid. The author has an hindex of 1, co-authored 1 publications receiving 71 citations.
TL;DR: Recombinant beta-toxin from Clostridium perfringenstype C was found to increase the conductance of bilayer lipid membranes by inducing channel activity, and the hypothesis that the lethal action of beta-Toxin is based on the formation of cation-selective pores in susceptible cells is supported.
Abstract: Beta-toxin is produced by Clostridium perfringens type B and C strains and is the primary lethal factor in the type C strains. No molecular mechanism has been elucidated for beta-toxin which could be used as a basis for investigating its role in the pathogenesis of these clostridial pathogens. It has been suggested that beta-toxin may be a pore-forming toxin on the basis of weak similarities (10% identity) between the primary structure of beta-toxin and those of the pore-forming alpha-hemolysin and gamma-hemolysin and the leukocidin from Staphylococcus aureus (9). Whether or not beta-toxin is cytotoxic remains unclear; only a single report has suggested that beta-toxin is weakly cytotoxic on intestinal 407 cells (6). However, a previous study suggested that the cytotoxicity associated with beta-toxin preparations was not linked to the beta-toxin itself, but to minor contaminants in the toxin preparation from C. perfringens (11). Recently, Steinthorsdottir et al. demonstrated that beta-toxin could induce the release of arachidonic acid and inositol from human umbilical vein endothelial cells (HUVECs) (32). No cytolytic effects were reported, suggesting that beta-toxin may not be necessarily lethal to these cells. Several other cell types were also tested by these investigators, but they were unresponsive to beta-toxin. C. perfringens type C strains cause necrotic enteritis primarily in pigs, chickens, cattle, sheep, and goats. Although adult animals can contract this disease, it most frequently occurs in the young of these species (34). Piglets are particularly susceptible to type C infections (5, 10, 18, 33), although a similar infection occurs in neonatal calves (7), lambs (8), and goats. During a type C infection, necrosis of the intestine can be extensive; death appears to be the result of toxemia with beta-toxin (reviewed in reference 29). Acute and peracute deaths frequently occur in these animals, suggesting that systemic effects of the toxin are important. In a C. perfringens type C disease of adult sheep, termed “struck,” the animals succumb to the infection so rapidly that they appear to have been struck by lightning. Prior to death, nervous signs such as tetani and opisthotonus have been observed in these animals (reviewed in reference 29), suggesting neurological involvement. Infection of humans by type C strains appears to be largely restricted to certain tribal populations in Papua New Guinea, although infrequent cases of type C infection have occurred in humans throughout the world. Type C infections result in necrotizing enterocolitis (“pigbel”) in these individuals after consumption of undercooked pork during certain ritualistic practices (13). Typically, type C necrotizing enterocolitis in humans resembles the disease in animals. The importance of beta-toxin in both animal and human disease has been demonstrated by immunization studies using a toxoid of beta-toxin. When immunized with the toxoid of beta-toxin, the Papua New Guinea tribespeople experienced a fivefold reduction in the incidence of necrotic enteritis (13), whereas a beta-toxin toxoid administered to infant pigs during an outbreak of necrotizing enterocolitis reduced mortality by approximately 30% (30). In the case of agriculturally important animals, vaccination against type C infections is universally advocated in order to avoid devastating losses. Therefore, beta-toxin plays a key role in the lethal outcome of type C infections, yet we know very little about its mechanism or the cell types it affects. The results presented below demonstrate that beta-toxin is an efficient pore-forming toxin which generates potential-dependent, cation-selective channels in membranes. The channels formed by beta-toxin exhibit characteristics that may provide some insight into the lethal activity of this toxin.
TL;DR: The incidence of Clostridium perfringens-associated necrotic enteritis in poultry has increased in countries that stopped using antibiotic growth promoters and the use of probiotic and prebiotic products has been suggested, but are not available for practical use in the field at the present time.
Abstract: The incidence of Clostridium perfringens-associated necrotic enteritis in poultry has increased in countries that stopped using antibiotic growth promoters. Necrotic enteritis and the subclinical form of C. perfringens infection in poultry are caused by C. perfringens type A, producing the alpha toxin, and to a lesser extent type C, producing both alpha toxin and beta toxin. Some strains of C. perfringens type A produce an enterotoxin at the moment of sporulation and are responsible for foodborne disease in humans. The mechanisms of colonization of the avian small intestinal tract and the factors involved in toxin production are largely unknown. It is generally accepted, however, that predisposing factors are required for these bacteria to colonize and cause disease in poultry. The best known predisposing factor is mucosal damage, caused by coccidiosis. Diets with high levels of indigestible, water-soluble non-starch polysaccharides, known to increase the viscosity of the intestinal contents, also predispose to necrotic enteritis. Standardized models are being developed for the reproduction of colonization of poultry by C. perfringens and the C. perfringens-associated necrotic enteritis. One such model is a combined infection with Eimeria species and C. perfringens. Few tools and strategies are available for prevention and control of C. perfringens in poultry. Vaccination against the pathogen and the use of probiotic and prebiotic products has been suggested, but are not available for practical use in the field at the present time. The most cost-effective control will probably be achieved by balancing the composition of the feed.
TL;DR: 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.
Abstract: 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 Tn916-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.
TL;DR: The Gram-positive pathogen Clostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract.
Abstract: The Gram-positive pathogenClostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (~25—35 kDa) size, although lacking in sequence homology, and (2) they generally act by forming pores or channels in plasma membranes of host cells. These enteric toxins include C. perfringens enterotoxin (CPE), which is responsible for the symptoms of a common human food poisoning and acts by forming pores after interacting with intestinal tight junction proteins. Two other C. perfringens enteric toxins, ɛ-toxin (a bioterrorism select agent) and β-toxin, cause veterinary enterotoxemias when absorbed from the intestines; β- and ɛ-toxins then apparently act by forming oligomeric pores in intestinal or extra-intestinal target tissues. The action of a newly discovered C. perfringens enteric toxin, β2 toxin, has not yet been defined but precedent suggests it might also be a pore-former. Experience with other clostridial toxins certainly warrants continued research on these C. perfringens enteric toxins to develop their potential as therapeutic agents and tools for cellular biology.
TL;DR: The present review indicates that the functional consequences of C3-induced ADP-ribosylation are more complex than previously suggested.
Abstract: C3-like exoenzymes comprise a family of seven bacterial ADP-ribosyltransferases, which selectively modify RhoA, B, and C at asparagine-41. Crystal structures of C3 exoenzymes are available, allowing novel insights into the structure-function relationships of these exoenzymes. Because ADP-ribosylation specifically inhibits the biological functions of the low-molecular mass GTPases, C3 exoenzymes are established pharmacological tools to study the cellular functions of Rho GTPases. Recent studies, however, indicate that the functional consequences of C3-induced ADP-ribosylation are more complex than previously suggested. In the present review the basic properties of C3 exoenzymes are briefly summarized and new findings are reviewed.
TL;DR: Clostridia are not normally considered to be zoonotic pathogens, although many species affect both humans and domestic animals, and three cases in which organisms occur in both food animals and humans are considered here.