By tracking what parasites eat and detailing the exact pathways down which they metabolize nutrients for growth, researchers in Australia believe they have revealed new drug targets for fighting the deadly tropical parasite Leishmania which infects 12 million and kills half a million people every year.
Led by Professor Malcolm McConville from the Bio21 Institute at the University of Melbourne, the researchers write about their work in the 5 August issue of The Journal of Biological Chemistry.
The analytical technique that the team has developed, which reveals which metabolic pathways are essential for parasite survival (even down to the particular atoms it uses for food), can be used to study the detailed metabolism of many infectious parasites and bacteria.
They chose to work on the genus Leishmania because it has a complex life cycle, and an ability to infect many animals, which makes treatment difficult and limits the effectiveness of any vaccine.
Leishmania is a single-celled parasite that causes the disease leishmaniasis, which currently affects humans in 88 countries. Depending on which species causes the disease, the infected person develops skin conditions or organ infection, which can be fatal.
The parasite lives in tiny sandflies and transfers to humans and other vertebrates when the insects bite them to get blood to make eggs.
McConville and colleagues labelled the carbon atoms in the parasite’s food source (sugar glucose), and using various cutting edge technologies, including nuclear magnetic resonance (NMR), and gas chromatography-mass spectrometry, they followed the atoms from ingestion into cells and then out again as secreted metabolites, thus mapping which metabolic pathways are essential to the parasite’s survival. These can the be used as potential targets for new drugs that block the pathways and literally starve the parasites to death.
McConville, who is also principal research fellow of the Australian National Health and Medical Research Council, told the media:
“This a very significant breakthrough in this field because the more we know about these dangerous pathogens and how they live, the better we can fight them with new, effective drugs.”
The problem with current drugs against parasites is they have enormous side effects, usually due to the fact they don’t target specific metabolic pathways.
“We now have a greater understanding of Leishmania and can develop specific drugs with minimal side effects,” said McConville.
Written by Catharine Paddock PhD