18 J. Glenn Songer and Francisco A. Uzal Several clostridial species, including Clostridium perfringens, Clostridium difficile, and Clostridium spiroforme, affect the intestinal tract of rabbits. This chapter describes enteric disease produced by C. spiroforme, which is considered the most prevalent clostridial pathogen responsible for rabbit enteric disease, particularly in young animals. This microorganism also causes enteric disease in hares. C. spiroforme is a helically coiled, anaerobic, Gram-positive, spore-forming bacillus, which consists of an aggregation of individual semicircular cells joined end to end (Figure 18.1). It belongs phylogenetically in cluster XVIII of the low G + C Gram-positive bacteria and is not a genuine member of the genus Clostridium (Chapter 1). This microorganism is isolated frequently from the cecal contents of rabbits with spontaneous diarrhea in numbers as high as 106 spores per gram of content. C. spiroforme may also be related to clindamycin-associated colitis in rabbits, although at a lower concentration. The presence of C. spiroforme toxin (CST) is a consistent finding in the cecal content of diarrheic but not of healthy rabbits, and CST has been proposed as being responsible for diarrhea, enterocolitis, and death in rabbits infected with this organism. Figure 18.1 Gram stain of a cecal smear of a rabbit with Clostridium spiroforme infection, showing the typical spiral chains of cells. CST is a binary toxin which, like other clostridial binary toxins such as C. botulinum C2 toxin, C. difficile transferase, C. perfringens iota toxin, as well as the Bacillus binary toxins, including Bacillus anthracis toxins, consists of two independent proteins, one being the binding component which mediates the internalization into the cell of the intracellularly active component and the other part the active toxin. Clostridial binary toxins are responsible for enteric disease, inducing actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray. CST is mouse lethal, dermonecrotic in guinea pigs, and neutralized by C. perfringens type E iota toxin antibodies. The cst genes have been cloned, allowing recombinant production of the enzyme (CSTa) and of the binding (CSTb) components of CST. CST has been shown to enter target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has also been recently identified as the host cell receptor of the binary toxins C. difficile transferase and C. perfringens iota toxin. CST, although not the related Clostridium botulinum C2 toxin, co-localizes with LSR during toxin uptake and trafficking to the endosomal compartments. The cell-binding (B) component of this AB toxin enters the cell via receptor-mediated endocytosis and once trafficked into the cytosol, the A component inhibits normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. C. spiroforme is acquired by the fecal–oral route and colonizes the terminal small intestine and cecum, where it produces CST, which is considered to be the main virulence factor of this microorganism. The actin cytoskeleton is the target of several clostridial ADP-ribosyltransferases, including CST. ADP-ribosylation inactivates regulatory Rho proteins and damages the organization of the actin cytoskeleton. As noted, CST ADP-ribosylates actin monomers, inhibiting actin polymerization. Much less is known about B component binding to cell-surface receptors, and little is known about the details of toxin biochemistry, cellular uptake machinery, and host-cell responses following toxin-mediated disruption of the cytoskeleton. Considerable further work is required to understand the detailed pathogenesis of infection, since this has not been investigated in any detail. No full-genome sequence of this organism has been completed to date, but it would no doubt be of immense value in providing the basis upon which to begin investigating the pathogenesis of infection by this neglected pathogenic Clostridium. The basis of the apparent restriction of this infection to lagomorphs (hares, rabbits) is one of many intriguing questions about this interesting and poorly investigated pathogen. In the case series of rabbit enteritis, two or more potentially pathogenic organisms have frequently been identified, emphasizing that several different organisms may be acting in concert to produce clinical disease. The similarity between C. spiroforme and anthrax toxins is of interest. Western blotting and ELISA show that the binding component of anthrax toxin shares epitopes with that of C. spiroforme toxin, which is closely related immunologically, but no functional complementation has been observed between iota toxin and anthrax toxin components. The binding components can form toxins active on macrophages only in combination with their respective enzymatic components. Agents which prevent acidification of endosomes do not have the same effects on anthrax toxin activity as they do on iota and C. spiroforme toxins. Therefore, the mechanisms of entry into the cells are presumably different. Since the binding components of anthrax toxins and iota toxin share a conserved putative translocation domain, these binding components could have a common mode of insertion into the cell membranes.
Diseases produced by Clostridium spiroforme
Introduction
Etiology
Pathogenesis
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
