New targets for anti-parasitic drugs

The mechanism by which the compound betaine, an anti-parasitic agent found in seaweed, works as a pesticide against nematode worms is reported in a paper published this week in Nature Neuroscience. By uncovering a mechanism of action for betaine, this study could help provide leads for the development of new molecules to overcome the increasing prevalence of multidrug resistance in parasitic worms.

Early farmers used seaweed as a natural pesticide to protect plants and livestock but the reason why seaweed was an effective pesticide was unclear. More recently, studies have shown that betaine—which is present in seaweed—arrests nematode larval development, but the molecular target and pathway for its effect still remained unknown.

Aude Peden and colleagues exposed nematode worms to betaine and identified mutations in two separate worm proteins that modulated the effect of this compound. One of these proteins was SNF-3, a molecule that transports betaine in and out of cells. When SNF-3 was mutated, worms hypercontracted and became paralyzed, possibly because of a failure in betaine clearance. Mutations in the other protein, a betaine receptor called ACR-23, made the worms impervious to the toxic effects of betaine and even prevented paralysis in the SNF-3 mutant worms. ACR-23 was expressed in neurons stimulating locomotion, which explained why normal activation of ACR-23 by betaine led worms to become hypercontracted, paralyzed and to eventually die. The authors thus identify a possible mechanism for the anti-parasitic effects of betaine.