Can weedkillers whack human parasites?
A paper in shows that herbicides can attack the parasite that causes the tropical disease toxoplasmosis. Kerri Smith explores the history of wielding weedkiller against human disease.
It’s a common infection caused by a parasite called Toxoplasma gondii, related to the malaria parasite Plasmodium falciparum. More than a quarter of the world’s population are infected with Toxoplasma, but it only causes disease if a person’s immune system is compromised. In mice and rats, its effects are somewhat different — the parasite extinguishes a mouse or rat’s fear of cats, which, by leading them to a feline end, gets the parasite into a new host.
What’s the new paper about?
The same substance that controls seed germination in plants has been found to govern how Toxoplasma gondii spreads from one cell to the next1. The hormone, called abscisic acid (ABA), has previously been found only in plants and some simple sea creatures such as sponges.
This plant-like trait can be exploited to defeat the parasite: certain herbicides kill Toxoplasma. And because humans lack this chemical pathway, the treatments should have no side effects.
Has weedkiller been effective on parasites before?
Yes. In 1998, opthalmologist Rima McLeod of the University of Chicago Medical Center and her colleagues found that the herbicide glyphosate slowed the growth of the malaria and toxoplasmosis parasites2. And in 2002, a team from the University of Tübingen in Germany and Albert Schweitzer Hospital in Lambaréné, Gabon, published a report of a successful trial of fosmidomycin, already in use as a herbicide and antibiotic, as a treatment for malaria3.
What became of that?
The trial treated the disease in 21 of the 27 people who took part, and the team went on to pursue clinical trials of fosmidomycin in other places and test drugs that work in a similar way. But they hit a couple of problems, says biochemist Hassan Jomaa of Justus Liebig University in Giessen, Germany, a co-author on the paper. One issue, he says, was that fosmidomycin treatment required four consecutive days of taking the drug rather than an easier-to-administer 'single shot'. Jomaa’s fledgling company, set up in 2000, found it difficult to get funding after the study was published.
Sounds like there’s already a precedent for this. What will the new result add?
Microbiologist David Sibley of Washington University in Missouri and his colleagues report that fluridone acts on parasites in a different way to other herbicides. These prevent parasites from replicating; fluridone stops them from communicating with each other, which stops their spread through the body.
ABA controls the transition between two stages of the parasite’s growth, from an initial burst of replication inside a cell to the spread to other cells. When this pathway is disrupted, the parasites can’t tell when to leave one cell and invade the next. Nobody had realized that the bugs were capable of this kind of population-level communication, but that is what fluridone disrupts.
Does this mean it’ll be a better treatment?
“There's no way to tell, really, but it does give a different line of attack,” Sibley says. A different mode of action might be a useful lead in the search for drugs to treat parasitic infections, says McLeod.
New leads are important when researchers are up against the problem of drug resistance. “Often different strategies can be combined for synergistic effects,” Sibley adds. His team tried fluridone on mice with toxoplasmosis, and the results were promising — the infection became much less severe.
- Nagamune, K. et al. Nature 451, 202-206 (2008).
- Roberts, F. et al. Nature 393, 801-805 (1998).
- Missinou, M. et al. Lancet 360, 1941-1942 (2002).