Effects of Clostridium perfringens iota toxin in the small intestine of mice

Abstract

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases.

Pathologic findings on ruminant enteric clostridial diseases reveal specificities and differences among iota and iota-like toxins

“…Stretch marks caused by inflammation were seen on the mucosal surface of the spiral colon, with edematous and inflamed mesenteric lymph nodes. The presence of Gram-positive bacilli adhered to the surface of the necrotic mucosa in parts of the intestinal tract were found, which reinforces the diagnosis of the action of ITX (Redondo et al, 2017).…”

“…Scientific studies have demonstrated the importance of murine models in elucidating mechanisms associated with disease pathogenesis, host response dynamics and the action of Clostridium sp toxins during infection (Ismail and Omoush, 2019). Recently, Batah et al, (2017) (Redondo et al, 2017).…”

The Inhibitory Effect of Cholera Toxin B Subunit on <i>Clostridium Perfringens</i> Iota-Toxin-Induced Cytotoxicity

“…1,3) Iota-toxin elicits fluid accumulation and histological damage in mouse ligated ileal loops. 19) In future, we will assess whether CTB decreases iota-toxininduced fluid accumulation and histological damage in ileal loops. Thus, CTB possesses potential for therapeutic application against iota-toxin-associated disease.…”

Unveiling the pathogenic mechanisms of Clostridium perfringens toxins and virulence factors

“…For ITX, present only in toxinotype E and associated with haemorrhagic enteritis in cattle ( Figure 3 ), it is described that the lipolysis-stimulated lipoprotein receptor (LSR) mediates the entry of toxin Ib into the host cell [ 56 ], allowing the formation of functional channels for ion movement and entry of Ia by endocytosis [ 57 ]. This interaction leads to degenerative changes in the mucosal epithelium of the small intestine, increased permeability of intestinal cell monolayers, and haemorrhagic lesions in the serosa and mucosa characteristic of enteritis ( Figure 2 d) [ 58 ].…”