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Biochimica Et Biophysica Acta Mar 2016Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as... (Review)
Review
Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.
Topics: ADP Ribose Transferases; Animals; Bacterial Toxins; Cell Membrane; Clostridium; Humans; Pore Forming Cytotoxic Proteins; Protein Multimerization
PubMed: 26278641
DOI: 10.1016/j.bbamem.2015.08.006 -
Toxins Sep 2014Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive... (Review)
Review
Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin.
Topics: Animals; Bacillus; Bacterial Infections; Bacterial Proteins; Bacterial Toxins; Clostridium; Gastrointestinal Diseases; Humans; Protein Conformation
PubMed: 25198129
DOI: 10.3390/toxins6092626 -
Brain, Behavior, and Immunity Nov 2022Despite inconsistent results across studies, emerging evidence suggests that the microbial micro-environment may be associated with autism spectrum disorder (ASD)....
BACKGROUND
Despite inconsistent results across studies, emerging evidence suggests that the microbial micro-environment may be associated with autism spectrum disorder (ASD). Geographical and cultural factors highly impact microbial profiles, and there is a shortage of data from East Asian populations. This study aimed to comprehensively characterize microbial profiles in an East Asian sample and explore whether gut microbiota contributes to clinical symptoms, emotional/behavioral problems, and GI symptoms in ASD.
METHODS
We assessed 82 boys and young men with ASD and 31 typically developing controls (TDC), aged 6-25 years. We analyzed the stool sample of all participants with 16S V3-V4 rRNA sequencing and correlated its profile with GI symptoms, autistic symptoms, and emotional/behavioral problems.
RESULTS
Autistic individuals, compared to TDC, had worse GI symptoms. There were no group differences in alpha diversity of species richness estimates (Shannon-wiener and Simpson diversity indices). Participants with ASD had an increased relative abundance of Fusobacterium, Ruminococcus torques group (at the genus level), and Bacteroides plebeius DSM 17135 (at the species level), while a decreased relative abundance of Ruminococcaceae UCG 013, Ervsipelotrichaceae UCG 003, Parasutterella, Clostridium sensu stricto 1, Turicibacter (at the genus level), and Clostridium spiroforme DSM 1552 and Intestinimonas butyriciproducens (at the species level). Altered taxonomic diversity in ASD significantly correlated with autistic symptoms, thought problems, delinquent behaviors, self dysregulation, and somatic complaints. We did not find an association between gut symptoms and gut microbial dysbiosis.
CONCLUSIONS
Our findings suggest that altered microbiota are associated with behavioral phenotypes but not GI symptoms in ASD. The function of the identified microbial profiles mainly involves the immune pathway, supporting the hypothesis of a complex relationship between altered microbiome, immune dysregulation, and ASD that may advance the discovery of molecular biomarkers for ASD.
Topics: Autism Spectrum Disorder; Autistic Disorder; Biomarkers; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Problem Behavior
PubMed: 36058421
DOI: 10.1016/j.bbi.2022.08.015 -
Anaerobe Oct 2018Several enteric clostridial diseases can affect humans and animals. Of these, the enteric infections caused by Clostridium perfringens and Clostridium difficile are... (Comparative Study)
Comparative Study Review
Several enteric clostridial diseases can affect humans and animals. Of these, the enteric infections caused by Clostridium perfringens and Clostridium difficile are amongst the most prevalent and they are reviewed here. C. perfringens type A strains encoding alpha toxin (CPA) are frequently associated with enteric disease of many animal mammalian species, but their role in these diseased mammals remains to be clarified. C. perfringens type B encoding CPA, beta (CPB) and epsilon (ETX) toxins causes necro-hemorrhagic enteritis, mostly in sheep, and these strains have been recently suggested to be involved in multiple sclerosis in humans, although evidence of this involvement is lacking. C. perfringens type C strains encode CPA and CPB and cause necrotizing enteritis in humans and animals, while CPA and ETX producing type D strains of C. perfringens produce enterotoxemia in sheep, goats and cattle, but are not known to cause spontaneous disease in humans. The role of C. perfringens type E in animal or human disease remains poorly defined. The newly revised toxinotype F encodes CPA and enterotoxin (CPE), the latter being responsible for food poisoning in humans, and the less prevalent antibiotic associated and sporadic diarrhea. The role of these strains in animal disease has not been fully described and remains controversial. Another newly created toxinotype, G, encodes CPA and necrotic enteritis toxin B-like (NetB), and is responsible for avian necrotic enteritis, but has not been associated with human disease. C. difficile produces colitis and/or enterocolitis in humans and multiple animal species. The main virulence factors of this microorganism are toxins A, B and an ADP-ribosyltransferase (CDT). Other clostridia causing enteric diseases in humans and/or animals are Clostridium spiroforme, Clostridium piliforme, Clostridium colinum, Clostridium sordellii, Clostridium chauvoei, Clostridium septicum, Clostridium botulinum, Clostridium butyricum and Clostridium neonatale. The zoonotic transmission of some, but not all these clostridsial species, has been demonstrated.
Topics: Animals; Cattle; Cattle Diseases; Clostridium; Clostridium Infections; Gastrointestinal Diseases; Goat Diseases; Goats; Humans; Sheep; Sheep Diseases
PubMed: 29883627
DOI: 10.1016/j.anaerobe.2018.06.002 -
Gut Microbes 2014The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward... (Review)
Review
The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions.
Topics: Bacterial Toxins; Clostridioides difficile; Humans; Prohibitins; Spores, Bacterial; Virulence Factors
PubMed: 25483328
DOI: 10.4161/19490976.2014.969632 -
Infection and Immunity Aug 1989The two components Sa (Mr, 44,000) and Sb (Mr, 92,000) of Clostridium spiroforme toxin were identified and characterized. Serological data permitted the identification...
The two components Sa (Mr, 44,000) and Sb (Mr, 92,000) of Clostridium spiroforme toxin were identified and characterized. Serological data permitted the identification of two groups of actin ADP-ribosylating clostridial toxins. The first consists of only C. botulinum C2. The second group includes spiroforme toxin, iota toxin of C. perfringens E, and an enzyme called CDT found in one strain of C. difficile, antibodies against which cross-react with all of the members of both groups. C. spiroforme toxin acted on cells by disrupting microfilaments by ADP-ribosylation of G actin. Toxicity was not blocked by 10 or 20 mM ammonium chloride and was only moderately inhibited by 30 mM NH4Cl. Inhibition of coated-pit formation in HEp-2 cells by potassium depletion strongly protected against the effect of C. spiroforme toxin. Toxicity was not blocked by incubation of HEp-2 cells and spiroforme toxin at 15 degrees C. These results suggest that this new binary toxin enters cells via the coated-pit-coated-vesicle pathway and might reach the cytoplasm at the same time as or before transfer to early endosomes.
Topics: ADP Ribose Transferases; Animals; Antigens, Bacterial; Bacterial Toxins; Carcinoma, Hepatocellular; Chlorocebus aethiops; Clostridium; Endocytosis; Humans; Liver Neoplasms; Mice; Poly(ADP-ribose) Polymerases; Rabbits; Tumor Cells, Cultured; Vero Cells
PubMed: 2545625
DOI: 10.1128/iai.57.8.2462-2469.1989 -
Scientific Reports Aug 2022Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to...
Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to identify gut microbiome-based biomarkers and detect their association with host gene expression in the initiation and progression of CRC by integrating analysis of the gut mucosal metagenome, RNA sequencing, and sociomedical factors. We performed metagenome and RNA sequencing on colonic mucosa samples from 13 patients with advanced CRC (ACRC), 10 patients with high-risk adenoma (HRA), and 7 normal control (NC) individuals. All participants completed a questionnaire on sociomedical factors. The interaction and correlation between changes in the microbiome and gene expression were assessed using bioinformatic analysis. When comparing HRA and NC samples, which can be considered to represent the process of tumor initiation, 28 genes and five microbiome species were analyzed with correlation plots. When comparing ACRC and HRA samples, which can be considered to represent the progression of CRC, seven bacterial species and 21 genes were analyzed. When comparing ACRC and NC samples, 16 genes and five bacterial species were analyzed, and four correlation plots were generated. A network visualizing the relationship between bacterial and host gene expression in the initiation and progression of CRC indicated that Clostridium spiroforme and Tyzzerella nexilis were hub bacteria in the development and progression of CRC. Our study revealed the interactions of and correlation between the colonic mucosal microbiome and host gene expression to identify potential roles of the microbiome in the initiation and progression of CRC. Our results provide gut microbiome-based biomarkers that may be potential diagnostic markers and therapeutic targets in patients with CRC.
Topics: Adenoma; Bacteria; Colorectal Neoplasms; Gastrointestinal Microbiome; Gene Expression; Humans; Intestinal Mucosa; Microbiota
PubMed: 35927305
DOI: 10.1038/s41598-022-17823-7 -
Frontiers in Cellular and Infection... 2011There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C.... (Review)
Review
There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C. perfringens, and C. spiroforme, cause enteric problems in animals as well as humans. These often fatal diseases can partly be attributed to binary protein toxins that follow a classic AB paradigm. Within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-ADP-ribosylation of globular actin by the A component. However, much less is known about B component binding to cell-surface receptors. These toxins share sequence homology amongst themselves and with those produced by another Gram-positive, spore-forming bacterium also commonly associated with soil and disease: Bacillus anthracis. This review focuses upon the iota and C2 families of clostridial binary toxins and includes: (1) basics of the bacterial source; (2) toxin biochemistry; (3) sophisticated cellular uptake machinery; and (4) host-cell responses following toxin-mediated disruption of the cytoskeleton. In summary, these protein toxins aid diverse enteric species within the genus Clostridium.
Topics: ADP Ribose Transferases; Adenosine Diphosphate Ribose; Animals; Bacterial Proteins; Bacterial Toxins; Botulinum Toxins; Clostridium; Clostridium Infections; Endocytosis; Host-Pathogen Interactions; Humans; Models, Molecular; Phylogeny
PubMed: 22919577
DOI: 10.3389/fcimb.2011.00011 -
Infection and Immunity Apr 2012Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis,...
Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor.
Topics: ADP Ribose Transferases; Bacillus megaterium; Bacterial Toxins; Botulinum Toxins; Caco-2 Cells; Cell Line; Clostridioides difficile; Clostridium; Clostridium Infections; Enterotoxins; HeLa Cells; Humans; Protein Binding; Receptors, LDL; Recombinant Proteins
PubMed: 22252869
DOI: 10.1128/IAI.06378-11 -
Journal of Clinical Microbiology Mar 1983A helically coiled, anaerobic, gram-positive sporeforming bacillus, identified as Clostridium spiroforme, was isolated from the cecal contents of all of 27 rabbits with...
A helically coiled, anaerobic, gram-positive sporeforming bacillus, identified as Clostridium spiroforme, was isolated from the cecal contents of all of 27 rabbits with spontaneous diarrhea, at a mean concentration of 10(6.0) spores per g of material. All of these rabbits also had a toxin present in their cecal contents that was neutralized by anti-Clostridium perfringens type E iota toxin, but not by other clostridial antitoxins. In addition, four rabbits with clindamycin-associated colitis were positive for C. spiroforme at a mean concentration of 10(4.5). All of these animals also had iota-like toxin present. Iota-like toxin was not detected in the cecal contents of 72 healthy animals, although C. spiroforme was found in two of these animals at a mean concentration of 10(6.0). C. spiroforme was shown to produce a toxin in vitro that was lethal to mice and caused dermonecrosis in guinea pigs. In all cases, this toxin was neutralized by anti-C. perfringens type E iota toxin.
Topics: Animals; Clindamycin; Clostridium; Clostridium Infections; Colitis; Diarrhea; Enterotoxemia; Enterotoxins; Guinea Pigs; Mice; Rabbits
PubMed: 6841578
DOI: 10.1128/jcm.17.3.414-418.1983