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The effect of disulfiram on egg shell formation in adult Trichuris muris
1United States Department of Agriculture, Parasite Biology and Epidemiology Laboratory, Beltsville, Maryland 20705, USA.
Abstract:
The effect of disulfiram on egg shell morphology in the parasitic nematode Trichuris muris was studied in vitro and in vivo. Daily disulfiram treatment of mice infected with T. muris beginning 25 days after infection and continuing for 26 days resulted in the production of malformed eggs by adult female worms in all treated groups. In addition, significantly fewer adult worms were found at necropsy in mice treated with 5.0 or 7.5 mg/kg/day of disulfiram as compared with mice treated with 2.5 mg/kg/day or control mice. Adult worms collected from infected, untreated mice and placed in aerobic culture for 5 days in media containing 4 or 8 micrograms/ml of disulfiram released malformed eggs into the culture medium after 30 hr in culture. Oral inoculation of naive mice with malformed eggs did not result in T. muris infections in the mice. The results of these studies suggest that inhibition of phenol oxidase results in disruption of normal egg production by T. muris females and that the enzyme might be a useful target in the development of control strategies aimed at nematode parasites that rely on phenol oxidase for egg shell hardening.
Insights
Disulfiram treatment malformed parasitic nematode eggs by inhibiting phenol oxidase. This disruption prevents successful infection, suggesting phenol oxidase as a target for parasite control.
Area of Science:
- Parasitology
- Nematology
- Drug Discovery
Background:
- The parasitic nematode Trichuris muris is a significant veterinary and human health concern.
- Understanding the biological mechanisms of nematode egg production is crucial for developing effective control strategies.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of disulfiram on the egg shell morphology of Trichuris muris.
- To evaluate the potential of disulfiram and its mechanism of action as a novel anti-parasitic strategy.
Main Methods:
- Mice infected with Trichuris muris were treated daily with varying doses of disulfiram.
- Adult worms were cultured in vitro with disulfiram, and egg morphology was assessed.
- Malformed eggs were used to inoculate naive mice to assess infectivity.
Main Results:
- Disulfiram treatment in vivo and in vitro led to the production of malformed Trichuris muris eggs.
- Higher doses of disulfiram significantly reduced the adult worm burden in infected mice.
- Malformed eggs failed to establish Trichuris muris infections in naive mice.
Conclusions:
- Disulfiram inhibits phenol oxidase, disrupting normal egg shell formation in Trichuris muris.
- The enzyme phenol oxidase is essential for egg shell hardening in this nematode.
- Targeting phenol oxidase presents a promising avenue for developing new nematode parasite control agents.