Attack of the nervous system by Clostridium perfringens Epsilon toxin: From disease to mode of action on neural cells

Abstract

Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far. ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats. This disease comprises several manifestations indicating the attack of the nervous system. This review aims to summarize the effects of ET on central nervous system. ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier. Therefore, it induces perivascular oedema and accumulates into brain. ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin. Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET. The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents. In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e.g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination. Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network. The precise mode of action of ET on neural cells remains to be determined.

Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology?

“…Murrell et al [83] first suggested that exotoxins could be a potential cause of MS, as humans are not natural hosts of C. perfringens types B or D [84–87]. Exotoxins bind to receptors present in the vascular system of the brain and in both myelinated and unmyelinated brain regions, such as the corpus callosum [88–91]. Osmolysis occurs upon binding to the receptor [92–96].…”

Clostridial pore-forming toxins: Powerful virulence factors

“…Toxin-dependent cell signaling leading to cell necrosis is not yet fully understood and includes ATP depletion, AMP-activated protein kinase stimulation, mitochondrial membrane permeabilization, and mitochondrial-nuclear translocation of apoptosis-inducing factor, which is a potent caspase-independent cell death factor. The early and rapid loss of intracellular K + induced by ETX and ATX, seems to be the early event leading to cell necrosis [105] (review in [106][107][108]. Change in cell membrane permeability with K + , Ca ++ , and ATP as the main signaling molecules is a common feature of PFTs [109].…”

Clostridium perfringens Epsilon Toxin: A Malevolent Molecule for Animals and Man?

“…C. perfringens Etx rapidly disrupts the blood-brain barrier, binds neuronal cells and causes lethality [31,52,56,60]. Among neuronal cell populations, the neurons are most susceptible followed by oligodendrocytes and astrocytes [61].…”