The 3D structure of ET has been resolved and presents similarities with the pore-forming toxin aerolysin produced by Aeromonas hydrophila species ( Cole et al., 2004; Gurcel et al.,

2006; Parker et al., 1994). For further details concerning ET mode of action see §6 and recent reviews written by Popoff (2011a) and by Bokori-Brown et al. (2011). Proliferation of C. perfringens type D in the intestinal tract and ensuing production of toxins causes enteric disease termed enterotoxaemia in sheep and goats, Epigenetics Compound Library whereas C. perfringens type B is associated with dysentery (sheep) and haemorrhagic enteritis (goats) and signs of enterotoxaemia (reviewed by McClane et al., 2006; Uzal and Songer, 2008). Enterotoxaemia caused by C. perfringens type D in sheep is a worldwide problem. The disease is most commonly observed in lambs ( Barker et al., 1993; Songer, 1996), frequent in goats ( Blackwell and Butler, 1992; Blackwell et al., 1991; Uzal and Kelly, 1996, 1997; Uzal et al., 1994) and adult sheep and calves ( Buxton CCI-779 concentration et al., 1981; Munday et al., 1973) but less frequent in adult cattle ( Radostits et al., 2000), and has been reported in deers, domesticated camels, horses ( Stubbing, 1990). Recently, a suspicious case has even been reported in a tiger ( Zeira et al., 2012). Naturally occurring enterotoxaemia is commonly depicted according to 3 grades of manifestations (per-acute, acute and sub-acute or chronic);

the severity of the disease being correlated to the amount of ET produced by C. perfringens. In per-acute form, sudden death of animals occurs without premonitory signs. In sheep, the acute form is characterized by a combination of severe neurological (as convulsions) and respiratory troubles; diarrhoea is infrequent. The recovery from the acute form of the disease is rare. In sheep, systemic lesions are observed (such as petechiae, brain and lung oedemas) with minor changes in the intestine ( Fernandez-Miyakawa et al., 2003; Uzal and Songer, 2008). At variance, the chronic form is rarely

observed in sheep suggesting very mild manifestations while the brain tissue displays signs of focal symmetric encephalomalacia (see below, §4) ( Uzal Farnesyltransferase and Songer, 2008). Contrary to what is observed in sheep, in goats, the acute form provoked by C. perfringens intoxication affects mostly young animals while chronic form of the disease is more frequent in adults. In goats, diarrhoea is the most frequent manifestation ( Uzal and Songer, 2008; Oliveira et al., 2010). Symptoms and manifestations observed either in the naturally occurring disease or after experimental intoxication (i.e. either by injecting C. perfringens in the gastro-intestinal tract or ET in the duodenum, intraperitoneally or intravenously) can be sorted into groups according to the altered-physiological system: intestinal, renal, pulmonary and nervous systems.