Nav: Home

Sweet success of parasite survival could also be its downfall

September 16, 2019

University of York scientists are part of an international team which has discovered how a parasite responsible for spreading a serious tropical disease protects itself from starvation once inside its human host.

The findings provide a new understanding of the metabolism of the Leishmania parasite and this new knowledge could potentially be used in its eradication. The disease the parasite causes is called Leishmaniasis and it is spread by the bite of sand flies. It kills between 20-40,000 people every year.

In a collaboration between the University of Melbourne and the University of York, researchers found that Leishmania make an unusual carbohydrate reserve, called mannogen, that protects them from fluctuating nutrient levels in the host, enabling their survival.

They then identified a new family of enzymes that use sugars scavenged from the host to make mannogen. University of York researchers defined the 3-D structure of these enzymes and this allowed researchers to map the evolution of this new enzyme family whose members acquired the ability to both make and degrade mannogen, and regulate the metabolism of these pathogens. This knowledge is now being used to identify drug molecules that bind and block enzyme activity and may be used to develop new therapies.

Professor Gideon Davies from the University of York's Department of Chemistry said: "Our three-dimensional structural insight provides new opportunities for drug design against this pathogen. We look forward to targeting the disease in future. The team of PhD students and York Chemistry MChem project students did a fantastic job of the structural analyses."

Professor Malcolm McConville from the University of Melbourne said: "As mannogen metabolism is critical for the survival of these parasites, developing inhibitors to block the enzymes that regulate this carbohydrate store is a potential way to specifically kill Leishmania parasites. We can exploit the parasite's food preference for mannogen and specifically target this metabolic pathway, without side-effects to humans.

"Similar enzymes and carbohydrates are made by other pathogens, such as the bacteria that cause tuberculosis, and this work may contribute to developing new classes of drugs to treat other infectious diseases."

Leishmania are able to persist for many years in their human host by hiding inside immune cells, such as macrophages. Macrophages are normally responsible for killing invading pathogens, but Leishmania are able to avoid this fate and grow stealthily within these host cells, eventually forming large 'granuloma' lesions that can lead to open ulcerating sores, organ damage and, in some cases, death.

Many people who carry the parasite remain asymptomatic, but immunosuppressed individuals, for example those with HIV/AIDs or suffering from malnutrition, are particularly vulnerable. Until recently very little was known about how Leishmania managed to grow within these host cells and resist most antibiotics.

Leishmaniasis is increasing in many regions of the world, including the Middle East, Africa and Central America where there are regional conflicts and breakdown in health services. There is currently no effective vaccine against it.
-end-


University of York

Related Metabolism Articles:

A new model of metabolism draws from thermodynamics and 'omics'
Scientists at EPFL have developed an algorithm that can model biochemical reactions from metabolism down to RNA synthesis with unprecedented accuracy.
A new way to control microbial metabolism
To help optimize microbes' ability to produce useful compounds but also maintain their own growth, MIT chemical engineers have devised a way to induce bacteria to switch between different metabolic pathways at different times.
Parasite manipulates algal metabolism for its own benefit
Researchers from the Max Planck Institute for Chemical Ecology and the universities of Jena and Frankfurt show that a pathogenic fungus alters the metabolism of its host unicellular algae, for its own purposes: the small bioactive substances that are formed in the process benefit the fungi's own propagation while preventing the algae from proliferating.
Lack of sleep affects fat metabolism
A restricted-sleep schedule built to resemble an American work week made study participants feel less full after a fatty meal and altered their lipid metabolism.
Mastering metabolism for shark and ray survival
Understanding the internal energy flow -- including the metabolism -- of large ocean creatures like sharks and rays could be key to their survival in a changing climate, according to a new study.
Rutgers researchers identify the origins of metabolism
A Rutgers-led study sheds light on one of the most enduring mysteries of science: How did metabolism -- the process by which life powers itself by converting energy from food into movement and growth -- begin?
Challenging metabolism may help fight disease
New research by Swansea University academics has shown that harnessing metabolism at a cellular level may help to relieve or heal a range of disorders.
How obesity affects vitamin D metabolism
A new Journal of Bone and Mineral Research study confirms that vitamin D supplementation is less effective in the presence of obesity, and it uncovers a biological mechanism to explain this observation.
Micro-control of liver metabolism
A new discovery has shed light on small RNAs called microRNAs in the liver that regulate fat and glucose metabolism.
Untangling the impacts of gut bacteria on drug metabolism
Individual drugs show variations in how successful or toxic they are, person to person.
More Metabolism News and Metabolism Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#555 Coronavirus
It's everywhere, and it felt disingenuous for us here at Science for the People to avoid it, so here is our episode on Coronavirus. It's ok to give this one a skip if this isn't what you want to listen to right now. Check out the links below for other great podcasts mentioned in the intro. Host Rachelle Saunders gets us up to date on what the Coronavirus is, how it spreads, and what we know and don't know with Dr Jason Kindrachuk, Assistant Professor in the Department of Medical Microbiology and infectious diseases at the University of Manitoba. And...
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.