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Title: Tunicamycins, a class of nucleoside antibiotics similar to corynetoxins of the Rathayibactor toxicus, increase susceptibility of mice to Neospora caninum

Author
item Tuo, Wenbin
item ZHANG, XICHEN - Jilin University
item CAO, LILI - Jilin University

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/15/2010
Publication Date: 11/30/2010
Citation: Tuo, W., Zhang, X., Cao, L. 2010. Tunicamycins, a class of nucleoside antibiotics similar to corynetoxins of the Rathayibactor toxicus, increase susceptibility of mice to Neospora caninum. Veterinary Parasitology. 177(1-2):13-29.

Interpretive Summary: Neosporosis is the leading cause of abortion in cattle. Neospora caninum-associated abortion may exhibit both endemic and epidemic patterns. It was reported that the epidemic outbreaks took place in the form of “abortion storms” and were not significantly correlated with seasonal changes or consumption of any particular feeds; and thus, the mechanisms by which the epidemic “abortion storms” are triggered remain unclear. Annual ryegrass toxicity (ARGT) is a fatal neurological disorder of livestock of Australia and South Africa. Similar disorder caused by ARGT was also shown in the US. The present study investigated whether animals pre-exposed to tunicamycins (TMs), a functional substitute for CTs, had a lowered resistance to sublethal experimental infection by N. caninum tachyzoites in mice. The results showed sublethal doses of N. caninum induced high mortality in TMs-treated mice in a dose dependent manner. The results suggest that CTs contaminated plants, when exposed to animals under natural conditions, may contribute to increased N. caninum-associated morbidity and mortality in affected animals.

Technical Abstract: Neosporosis is the leading cause of abortion in cattle. Neospora caninum-associated abortion may exhibit both endemic and epidemic patterns. It was reported that the epidemic outbreaks took place in the form of “abortion storms” and were not significantly correlated with seasonal changes or consumption of any particular feeds; and thus, the mechanisms by which the epidemic “abortion storms” are triggered remain unclear. Annual ryegrass toxicity (ARGT) is a severe or fatal neurological disorder of livestock of Australia and South Africa. This disorder is caused by ingestion of several plant genera (Lolium, polypogon, and Agrostis) colonized by a nematode (Anguina sp) and a bacterium, Rathayibacter toxicus. Corynetoxins (CTs) produced by R. toxicus contaminate plants which are in turn ingested by sheep and cattle, causing severe or often fatal hepatocerebral disorders in affected animals. We hypothesize that N. caninum-associated fetal deaths and abortions in cattle may be potentiated by pre-exposure of sublethal levels of CTs-contaminated plants prior to N. caninum infection or reactivation of a latent infection. The exposure of sublethal CTs may not cause clinical diseases, but may increase susceptibility to pathogens such as N. caninum. Indeed, CTs poisoning surviving pregnant sheep can have up to 10% abortions. The present study investigated whether animals pre-exposed to tunicamycins (TMs), a functional substitute for CTs, had a lowered resistance to sublethal experimental infection by N. caninum tachyzoites in mice. The results showed that sublethal doses of TMs or N. caninum alone did not cause significant deaths. Sublethal doses of N. caninum induced high mortality in TMs-treated mice in a dose dependent manner. When mice were treated with a low dose of TMs (5ug/mouse), as few as 2.5 x 10-6 tachyzoites were needed to induce more than 30% of mortality which is equivalent to the mortality rate caused by 40 x 10-6 tachyzoites. The results suggest that CTs contaminated plants, when exposed to animals under natural conditions, may contribute to increased N. caninum-associated morbidity and mortality in affected animals.