Twenty years ago, biologists made the astonishing discovery that the malaria parasite, then killing almost a million people a year, had genes previously considered unique to plants. The announcement generated excitement from the hope that herbicides might be redeployed to fight this scourge. Instead, it seems, the benefits may go the other way, with existing malaria drugs offering potential as novel herbicides.
Apicomplexa parasites, malaria included, share the shikimate pathway and subunits called chloroplasts with plants, but not animals. Consequently, molecules that interfere with this pathway might be harmless to humans while controlling the parasites. Research on using herbicides has been done, but has now largely been abandoned with the discovery that most of chloroplast's functions are no longer essential to the survival of the malaria parasite when inside the human body.
At the University of Western Australia, Dr Keith Stubbs and Dr Joshua Mylne wondered if we shouldn't be looking at things in the other direction. “Herbicides are integral for modern day agriculture, but the spiralling costs to develop new herbicides have hindered their progress,” Mylne said in a statement. As with pesticides or antibiotics, natural selection favors resistant varieties, whose spread undermines the effectiveness of our attempts to kill them.
“In the past 30 years, no truly new herbicidal molecule has entered the agrochemical market,” Stubbs added. “By using tiny seeds of the model plant Arabidopsis we examined a library of antimalarial compounds and selected the best one – MMV006188. We then examined several variations of it to determine which points were important for its potency.” In Angewandte Chemie, Mylne and Stubbs report that MMv006188 proved as lethal to Arabidopsis as some existing commercial herbicides.
Mylne told IFLScience that MMV006188 was chosen because it works in soil, while some of the other anti-malaria drugs don't function well outside specific substrates. Moreover, its physical and chemical properties looked more like those of existing effective herbicides than some of the alternatives. Nevertheless, there are plenty more antimalarial options to explore.
The reason the malaria to herbicide route may prove more effective than the reverse, Mylne noted, is that some of the features the parasite shares with plants, such as ways to make amino acids, are not essential to its survival when it has access to human blood. Plants, which need to make all their complex molecules for themselves, die if these functions are blocked.
The potential benefits are not restricted to agriculture. The authors expect that by examining these established drugs from a new angle, we may learn more about how they work – something that is often poorly understood at the moment. Such knowledge could help us design versions that target malaria more effectively.
