Clostridium and Bacillus Binary Enterotoxins:  Bad for the Bowels, and Eukaryotic Being

Stiles, Bradley G.; Pradhan, Kisha; Fleming, Jodie M.; Samy, Ramar Perumal; Barth, Holger; Popoff, Michel R.

doi:10.3390/toxins6092626

Cited by 69 publications

(85 citation statements)

References 207 publications

(361 reference statements)

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“…C lostridium botulinum produces a binary toxin, C2, which consists of two nonlinked proteins called C2I (active enzymatic component) and C2II (binding component) (1)(2)(3)(4). The two components represent separate proteins, which are devoid of toxic activity when injected alone (4).…”

mentioning

confidence: 99%

“…C2I mono-ADP-ribosylates G-actin at arginine-177, which converts G-actin into a capping molecule and interferes with the additional polymerization of actin filaments. This leads to actin filament depolymerization and cell rounding (1,3). C2 toxin is a member of the binary actin-ADP-ribosylating toxin family.…”

mentioning

confidence: 99%

“…C2 toxin is a member of the binary actin-ADP-ribosylating toxin family. Members of this toxin family include Clostridium perfringens iota-toxin, Clostridium spiroforme iota-like toxin, Clostridium difficile ADP-ribosyltransferase, and vegetative insecticidal protein from Bacillus cereus (1)(2)(3)(4).…”

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confidence: 99%

“…Binding of C2I to membrane-bound C2IIa oligomers in lipid rafts induced the activation of phosphatidylinositol 3-kinase (PI3K), which in turn caused C2 toxin internalization via a lipid raft-mediated process (3,6). After endocytosis of C2 toxin, it was trafficked to early endosomes (1,3,7).…”

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confidence: 99%

“…The oligomer of C2IIa entered the endosomal membrane under acidic conditions and formed pores. Thereafter, C2I was translocated in an unfolded conformation through the endosomal membranes into the cytosol via the C2IIa pore (1,3). The membrane translocation of C2I was reported to be facilitated by the host cell factors Hsp90 (8), cyclophilin A (9), and FK506-binding protein (10).…”

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Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity

et al. 2017

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Clostridium botulinum C2 toxin consists of an enzyme component (C2I) and a binding component (C2II). Activated C2II (C2IIa) binds to a cell receptor, giving rise to lipid raft-dependent oligomerization, and it then assembles with C2I. The whole toxin complex is then endocytosed into the cytosol, resulting in the destruction of the actin cytoskeleton and cell rounding. Here, we showed that C2 toxin requires acid sphingomyelinase (ASMase) activity during internalization. In this study, inhibitors of ASMase and lysosomal exocytosis blocked C2 toxin-induced cell rounding. C2IIa induced Ca 2ϩ influx from the extracellular medium to cells. C2 toxininduced cell rounding was enhanced in the presence of Ca 2ϩ . ASMase was released extracellularly when cells were incubated with C2IIa in the presence of Ca 2ϩ . Small interfering RNA (siRNA) knockdown of ASMase reduced C2 toxin-induced cell rounding. ASMase hydrolyzes sphingomyelin to ceramide on the outer leaflet of the membrane at acidic pH. Ceramide was detected in cytoplasmic vesicles containing C2IIa. These results indicated that ASMase activity is necessary for the efficient internalization of C2 toxin into cells. Inhibitors of ASMase may confer protection against infection.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity

et al. 2017

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Brief Description of Animal Pathogenic Clostridia

Prescott¹

2016

Clostridial Diseases of Animals

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Clostridium, Clostridioides , and Other Clostridia

Kuijper,

Reubsaet,

Barbut

2023

ClinMicroNow

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The genus Clostridium comprises obligately anaerobic (or occasionally aerotolerant), Gram‐positive rods commonly found in soil, water, and gastrointestinal tracts of insects and animals, as well as humans. Accurate, definitive identification is needed to better define the role of clostridia in disease, to aid the clinician in selecting optimal treatment, and for public health purposes (e.g., hospital‐acquired Clostridioides difficile disease ). The isolation of a Clostridium species from a clinical specimen, even a blood culture, may or may not be significant clinically, and culture results should be interpreted in relation to the clinical findings for the patient. Identification of clostridia in specimens from sites of infection due to mixed organisms can be time‐consuming and expensive. Typing of Clostridioides difficile fosters understanding of the epidemiology of infections and has become increasingly important with the emergence of outbreaks caused by hypervirulent strains.

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Clostridium and Bacillus Binary Enterotoxins: Bad for the Bowels, and Eukaryotic Being

Cited by 69 publications

References 207 publications

Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity

Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity

Brief Description of Animal Pathogenic Clostridia

Clostridium, Clostridioides , and Other Clostridia

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