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 The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

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: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>