Plant-like protein underpins common parasites' ability to infect

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Washington, Jan 10 : Researchers at Washington University School of Medicine have revealed that Toxoplasma gondii, a common human parasite, uses a plant-like protein for signalling when to increase its numbers and when to be dormant.

T. gondii. is found in one in every four humans causing serious disease in patients with weakened immune systems.

However, in rare cases infection in healthy patients may lead to serious eye or central nervous system disease, or congenital defects in the foetuses of pregnant women.

The researchers were able to block the production of the molecule, known as abscisic acid (ABA), with the plant herbicide.

"As a target for drug development, this pathway is very attractive for several reasons," Nature quoted L. David Sibley lead author and professor of molecular microbiology.

"For example, because of its many roles in plant biology, we already have several inhibitors for it. Also, the plant-like nature of the target decreases the chances that blocking it with a drug will have significant negative side effects in human patients," he added.

T. gondii and those responsible for malaria include many plant-like pathways, or groups of genes or proteins put to work for a specific biological task.

ABA plays a vital role in regulating flowering and seed dormancy.

A string of experiments by Nagamune, assistant professor at Tsukuba University in Japan revealed that ABA helped the parasites to control their reproductive cycle by communicating with each other in the host cell.

When the parasites sensed high levels of ABA, they come out of host cells, else stay in it and remain dormant.

"Signals are sometimes even better targets for drug development than biosynthetic pathways," said Sibley.

"Taking out a biosynthetic pathway means you take away one thing from the parasite. But if you can successfully disable a key signal, this may potentially disrupt many more aspects of the parasite's metabolism, he added. "

After examining the online databases and botanists at the Donald Danforth Plant Science Center in St. Louis and elsewhere, researchers identified a class of herbicides that block ABA production and are already in commercial use and have been examined for low toxicity to animals. The study conducted over mice revealed that low doses of the herbicide averted lethal T. gondii infection.

After treating the infected mice with the herbicide the number of parasites reduced during the initial infection and also reduced the chronic burden.

The study is published in the Journal Nature.

ANI

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