Toxins of ClostridiumBotulinum neurotoxins (BoNTs) are the most potent natural toxins known. The family of BoNTs comprises of seven antigenically distinct serotypes (A to G) that are produced by various toxigenic strains of spore-forming anaerobic Clostridium botulinum. They act as metalloproteinases that enter peripheral cholinergic nerve terminals and cleave proteins that are crucial components of the neuroexocytosis apparatus, causing a persistent but reversible inhibition of neurotransmitter release resulting in flaccid muscle paralysis.
Apart from being the sole causative agent of the deadly food poisoning disease, botulism, BoNTs pose a major biological warfare threat due to their extreme toxicity and easy production. They are used as powerful tools to treat an ever expanding list of medical conditions (Proft, T. 2009). A better understanding of the structure-function relationship of clostridial neurotoxins will help decipher their molecular mode of action and also provide a greater understanding of the potential use of their individual domains in answering more fundamental questions of neuroexocytosis. It is also critical for designing effective specific inhibitors to counter botulism biothreat and for the development of new therapeutics (Proft, T. 2009).
Clostridium Food PoisoningClostridium botulinum produces extremely potent neurotoxins that result in the severe neuroparalytic disease, botulism. Although of lower lethality, the enterotoxin produced by Clostridium perfringens, during sporulation of vegetative cells in the host intestine, still results in debilitating acute diarrhea and abdominal pain. Sales of refrigerated, processed foods of extended durability including sous-vide foods, chilled ready-to-eat meals, and cook-chill foods have increased over recent years. As a result of conditions accommodating growth, anaerobic spore-formers have been identified as the primary microbiological concerns in these foods. Heightened awareness over intentional food source tampering with botulinum neurotoxin has arisen with respect to genes encoding the toxins that are capable of transfer to nontoxigenic clostridia. Similarly, enterotoxin produced by Clostridium perfringens and the genomic location of the cpe gene has epidemiologic significance for understanding the capability to cause foodborne disease in humans. Unique characteristics and virulence factors of Clostridium botulinum and Clostridium perfringens make them foodborne hazards in the food supply (Fratamico et al 2008))
Spores of ClostridiumBacteria of the genera Bacillus and Clostridium can be found in two distinct states. In the vegetative state, the bacterium is metabolically active and uses available nutrients to grow and divide by binary fission, a process that generates two identical daughter cells. By contrast, when nutrients are scarce, a developmental program of endospore formation (sporulation) is initiated, resulting in the production of a highly resistant spore (Graumann, P. 2007). In the spore state, the bacterium is metabolically dormant, and its genetic material, protected in the core of the spore, can endure a variety of challenges, including radiation, heat and chemicals. Sporulation is a complex process, which requires the generation of two distinct cell types: a forespore and a larger mother cell. The progression of the developmental program is controlled by two exquisitely regulated cell type-specific lines of gene expression that run in parallel and are connected at the post-transcriptional level. Various genetic screens and genome-wide transcriptional analyses have identified more than 600 genes that are expressed in the course of sporulation. The function of several of these genes has been characterized in detail and subcellular localization data are available for more than 70 sporulation proteins (Graumann, P. 2007). Sporulation constitutes one of the best characterized developmental programs at the molecular and cellular levels.
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