Clostridium perfringens toxinotypes in Ruminants

Clostridium perfringens is involved in several clostridial diseases of ruminants. The most common is enterotoxaemia, which affects both cattle and small ruminants. But this bacterium is also implicated in other syndromes such as Hemorrhagic Bowel Syndrome in cattle, yellow lamb disease in young sheep and certain neonatal enteritis in calves.

The toxins produced differ between Clostridium perfringens toxinotypes

Clostridium perfringens produces toxins that cause disease. The main Clostridium perfringens toxins, known as major toxins, are alpha toxin, beta toxin, epsilon toxin and iota toxin. Recently, two other major toxins have been identified: CPE toxin and NetB toxin (Rood et al., 2008). However, the pathogenic role of these two toxins has not been demonstrated in ruminants. Not all Clostridium perfringens produce all these toxins. Depending on their ability to secrete these different toxins, bacteria are classified into toxinotypes, as shown in Table 1. For example, toxinotype A produces only the alpha major toxin, while toxinotype B produces the alpha, beta and epsilon major toxins.

The basis of this nomenclature dates back to Wilsdon's work in the 1930s (Glenny et al., 1933). Since then, several changes have been made to this classification. In 1964, 5 toxinotypes (A, B, C, D and E) were identified (Sterne and Warrack, 1964). This classification is still valid. However, in 2008, thanks to molecular biology, it was proposed to add two toxinotypes (F and G) to the 5 historical toxinotypes. 

In ruminants, toxinotype A is the most frequent

In cattle, several typing studies of Clostridium perfringens strains carried out on samples from sick or healthy animals have shown that only toxinotype A is present (Daube et al., 1996; Manteca et al., 1999). However, it is also possible that toxinotypes B, C and E may sometimes be encountered, particularly in calves (Songer, 1996; Uzal et al., 2016a; Uzal et al., 2016b; Songer 2016).

In small ruminants, the distribution of the different toxinotypes is more variable. In sheep, toxinotypes A, B, C and D have been encountered in varying proportions depending on the study, but in most cases toxinotype A predominates (Daube et al., 1996; Kalender et al., 2005; Ahsani et al., 2010; Moustafa et al., 2022). In the case of goats, a hybridization study of the strains showed that toxinotype A represented 80% of the strains isolated; the other 20% were linked to toxinotype D (Daube et al., 1996).

It therefore appears that toxinotype A is the predominant toxinotype in domestic ruminants. Unlike the other toxinotypes, toxinotype A produces only one major toxin, alpha toxin. This toxin is therefore responsible for a large proportion of the clinical manifestations attributable to Clostridium perfringens in cattle, sheep and goats.

Key messages

• There are 7 toxinotypes of Clostridium perfringens and 6 major toxins
• Toxin alpha is produced by all the toxinotypes
• In ruminants, the toxinotype A, which produces only the major toxin alpha, is the most common

References

Ahsani, M. R., Mohammadabadi, M. R., & Shamsaddini, M. B. (2010). Clostridium perfringens isolate typing by multiplex PCR. Journal of Venomous Animals and Toxins including Tropical Diseases, 16, 573-578.

Daube, G., Simon, P., Limbourg, B., Manteca, C., Mainil, J., & Kaeckenbeeck, A. (1996). Hybridization of 2,659 Clostridium perfringens isolates with gene probes for seven toxins (alpha, beta, epsilon, iota, theta, mu, and enterotoxin) and for sialidase. American journal of veterinary research, 57(4).

Kalender, H., Ertas, H. B., Cetinkaya, B., Muz, A., Arslan, N., & Kilic, A. (2005). Typing of isolates of Clostridium perfringens from healthy and diseased sheep by multiplex PCR. Veterinarni Medicina-Praha-, 50(10), 439.

Manteca, C., Daube, G., & Mainil, J. (1999). Etude du rôle de Clostridium perfringens dans l'entérotoxémie bovine. Bulletin et mémoires de l'Académie Royale de Médecine de Belgique, 154(6, Pt 2).

Moustafa, S., Zakaria, I., Moustafa, A., AboSakaya, R., & Selim, A. (2022). Molecular epidemiology and genetic characterization of Clostridium perfringens infections in lambs. Microbial Pathogenesis, 173, 105822.

Rood, J. I., Adams, V., Lacey, J., Lyras, D., McClane, B. A., Melville, S. B., ... & Van Immerseel, F. (2018). Expansion of the Clostridium perfringens toxin-based typing scheme. Anaerobe, 53, 5-10.

Glenny A.T., Barr M., Llewwllyn-Jones M., Dalling T., Ross H.E., Multiple toxins produced by some organisms of the Cl. wlechii group, J. Pathol. Bacteriol. 37 (1933) 53-74.

Sterne M.,  Warrack G.H., The types of Clostridium perfringens, J. Pathol. Bacteriol. 88 (1964) 279-283.

Songer, J. G. (1996). Clostridial enteric diseases of domestic animals. Clinical microbiology reviews, 9(2), 216-234.

Songer, J. G. (2016). Infections by Clostridium perfringens type E. Clostridial Diseases of Animals; Uzal, FA, Songer, JG, Prescott, JF, Popoff, MR, Eds, 173-176.

Uzal, F. A., Songer, J. G., Prescott, J. F., & Popoff, M. R. (2016). Infections by Clostridium perfringens type B. Clostridial Diseases of Animals, 139-142.

Uzal, F. A., Giannitti, F., Finnie, J. W., & García, J. P. (2016). Diseases produced by Clostridium perfringens type D. Clostridial Diseases of Animals; Wiley Blackwell: Ames, IA, USA, 157-172.