Abstract
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.
Highlights
The Clostridium and Bacillus genera represent ubiquitous bacilli commonly found in soil, water, and gastrointestinal tracts of insects and animals, as well as humans
C. difficile, C. perfringens and C. spiroforme are all associated with gastrointestinal diseases in humans and/or animals [1,4,5,34,86,102], and the synthesis of common binary enterotoxins with interchangeable protein components likely reveals a shared evolutionary path for these ubiquitous pathogens in a common niche
Relative to enzymatic components of the other binary enterotoxins, the iota b (Ib) docking region on iota a (Ia) is more centrally located within the N-terminal domain [136,159], versus C2I residues 1–87 that interact with C2II (137) or CDTa residues 1–240 docking to CDTb [101]
Summary
The Clostridium and Bacillus genera represent ubiquitous bacilli commonly found in soil, water, and gastrointestinal tracts of insects and animals, as well as humans. Both genera grow in low-oxygen environments; the clostridia are better adapted for anaerobic life with varying aerotolerance among different species. The similarities, and dissimilarities, among these protein toxins suggest interesting evolutionary routes employed by some pathogenic Clostridium and Bacillus species Common themes for these bacterial binary enterotoxins are: (1) the A and B components are secreted from the bacterium as separate proteins (not a holotoxin); and (2) enzymatic modification of globular (G) actin that destroys the filamentous (F) actin-based cytoskeleton and the intoxicated cell [6]
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