Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An ounce of prevention: Research advances on 'scourge' of transplant wards

28.08.2015

The fungus Cryptococcus causes meningitis, a brain disease that kills about 1 million people each year -- mainly those with impaired immune systems due to AIDS, cancer treatment or an organ transplant. It's difficult to treat because fungi are genetically quite similar to humans, so compounds that affect fungi tend to have toxic side effects for patients.

Now, in one of the most detailed studies of how a dormant fungal spore transforms itself into a disease-causing yeast, researchers at the University of Wisconsin-Madison have identified 18 proteins that play a role in spore formation and germination. The findings raises the possibility of preventing the disease by blocking the spores' germination.


This is a spore of the deadly human fungal pathogen Cryptococcus (green) germinates into a yeast (yellow). Germination takes about 16 hours. Afterwards, the new yeast begins to reproduce by forming a bud (orange).

Credit: Christina Hull, University of Wisconsin-Madison

Spores are tough, resilient capsules that are made via sexual reproduction on trees and in soil that can remain dormant for years. Cryptococcus spores are apparently harmless until they are dispersed by wind or water and find a suitable environment where they can transform themselves into a yeast cell.

"When you inhale a spore, if it can't grow, it can't cause disease," says study leader Christina Hull, an associate professor of biomolecular chemistry. "Spores are dormant; they hang out until they find a place to grow into yeast, and the human lung is a good place. From there, the yeast can travel to the brain."

Once symptoms of cryptococcal meningitis appear, "the patient has billions of Cryptococcus yeasts growing in the brain," Hull says. "If you could prevent spores from activating, that might be a preventive therapy for immunocompromised patients so even if they inhale a spore, it cannot grow. That could be huge."

As reported today in PLOS Genetics, Hull, graduate student Mingwei Huang and UW-Madison colleagues Joshua Coon, David Beebe and Alex Hebert implicated 18 proteins and the genes that make them in Cryptococcus spore biology.

The study provides a rare look at a common process that is essential for disease transmission. Until now, Hull says, "it's been very difficult to isolate Cryptococcus spores from other cell types, so people have not spent much time looking at the issue of germination."

The transformation from spore to yeast "requires a change from one cell type to another, so many things must happen," Hull says. "Spores have a thick, protective coat that they must break down. What molecules allow that to happen? Now we can start to parse out exactly what it takes for a spore to turn into yeast."

The researchers deleted the genes for the 18 proteins in question and studied the resulting mutants. Hull was surprised to discover that most of the genes are involved in the process that forms a spore in the first place.

As the mutant spores grew, one gene that is necessary specifically for germination attracted additional attention. Already, Hull and colleagues are screening candidate drugs -- or, ideally, drugs that are already on the market -- at the Small Molecule Screening Facility on campus, looking for something that interferes with germination.

Hull is funded by The Hartwell Foundation of Memphis, Tennessee, to find treatments for fungal diseases, including some forms of childhood asthma. She says the results reported today may also apply to the kind of asthma caused by mold -- a common term for some fungi. "Increasingly, we are seeing that allergic asthma can be caused by fungi," Hull says. "If we can understand how fungal spores germinate, we could make some advances in treating -- perhaps even preventing -- some types of childhood asthma."

Scientific progress takes time, Hull says, but technical improvements developed by Coon, an expert in high-precision mass spectrometry, and Beebe, who invents microscale fluid flow devices, are allowing experiments once considered impossible. "I've been working on the basic biology of Cryptococcus since 2000," she says. "By marrying basic research discoveries from my laboratory with technological advances of my collaborators, we now have an exciting opportunity to identify and develop antifungal compounds that inhibit spore germination."

It's the old story about an ounce of prevention, Hull says. "If a spore enters the lung, it's not going to cause disease unless it can grow. If we develop drugs to stop fungi from making the transition from dormant spore to growing yeast, we can prevent disease in vulnerable patients and ultimately save lives."

###

CONTACT: Christina Hull, cmhull@wisc.edu, (608) 265-5441 (prefers email for first contact)

DOWNLOAD IMAGE: https://uwmadison.box.com/hull-fungus

David Tenenbaum, (608) 265-8549, djtenenb@wisc.edu

Christina Hull | EurekAlert!

Further reports about: Cryptococcus childhood asthma drugs fungi genes germination lung spores transplant

More articles from Health and Medicine:

nachricht Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

nachricht New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>