Genomics of Clostridium Botulinum and Clostridium Perfringens

This organism produces one of the most potent and deadly neurotoxins known, a botulinum toxin that prevents the release of acetylcholine at the neuromuscular junction, thereby inhibiting muscle contraction and causing paralysis. In most cases the diseased person dies of asphyxiation as a result of paralysis of chest muscles involved in breathing. The spores are heat-resistant and can survive in inadequately heated, prepared, or processed foods. Spores germinate under favorable conditions (anaerobiosis and substrate-rich environment) and bacteria start propagating very rapidly, producing the toxin.

Botulinum toxin, and C. botulinum cells, has been found in a wide variety of foods, including canned ones. Almost any food that has a high pH (above 4.6) can support growth of the bacterium. Honey is the most common vehicle for infection in infants. Food poisoning through C. botulinum is the most frequent type of infection caused by this bacterium. The wound botulism that occurs when C. botulinum infects an individual via an open wound is much rarer and is very similar to tetanus disease. There are several types of botulinum toxin known (type A through type F), all of them being neurotoxic polypeptides. The most common and widely distributed are strains and serovars of C. botulinum that produce type A toxin. This toxin finds its use in various applications requiring neuroparalitic intervention, including cosmetology (Botox ®).

Clostridium perfringens

This organism is a causative agent of a wide spectrum of necrotic enterotoxicoses. In humans it is responsible for such diseases as gas gangrene (clostridial myonecrosis), food poisoning, necrotizing enterocolitis of infants and enteritis necroticans (pigbel). It also causes such animal diseases as lamb dysentery, ovine enterotoxemia (struck), pulpy kidney disease in lambs and other enterotoxemias in lambs and calves.

The bacterium is one of the most widely distributed pathogens in nature. It is commonly found in the environment (soil, sewage) and in the animal and human gastrointestinal tract as a member of the normal microflora. It is a fast growing (generation time 8-10 min) anaerobic flesh-eater. Active fermentative growth is accompanied by profuse generation of molecular hydrogen and carbon dioxide. Unlike most other clostridia, C. perfringens is non-motile. It is also oxygen tolerant which makes it an easy object to work with in laboratories. Systems for genetic manipulation of C. perfringens have been developed and the species became a model organism in clostridial genetic studies.

Known isolates belong to five distinct types (A, B, C, D, and E) that are distinguished based on the specific extracellular toxins they produce. Each of the toxins is responsible for a specific disease syndrome. Type A strains that cause gas gangrene produce toxin alpha (phospholypase C), theta (hemolysin), kappa (collagenase), mu (hyaluronidase), nu (DNAse) and neuraminidase which are all the enzymatic factors aiding the bacterium in invading and destruction of the host tissues.

Collaborators

Jonathan Badger
JCVI

Ian Paulsen
Department of Chemistry and Biomolecular Sciences, Macquarie University

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