Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fungus uses copper detoxification as crafty defense mechanism

15.03.2013
A potentially lethal fungal infection appears to gain virulence by being able to anticipate and disarm a hostile immune attack in the lungs, according to findings by researchers at Duke Medicine.

Defense mechanisms used by the fungus Cryptococcus neoformans enable it to lead to fatal meningitis, which is one of the opportunistic infections often associated with death in HIV/AIDS patients, organ transplant recipients, diabetics and other immunosuppressed patients. In describing the complex process of how C. neoformans averts destruction in the lungs of mice, the Duke researchers have opened new options for drug development.

"Very few antifungal drugs are effective, so we need to identify the Achilles' heel of these fungal pathogens," said Dennis J. Thiele, PhD, the George Barth Geller Professor of Pharmacology and Cancer Biology at Duke University. Thiele is senior author of a study published March 13, 2013, in the journal Cell Host & Microbe. "With this research we may be closer to understanding how this fungal pathogen evades death in its host, and hopefully be closer to finding effective treatments."

Found in the environment, C. neoformans spores can be inhaled and cause infection, particularly when people have weakened immune systems. The Centers for Disease Control and Prevention estimates that worldwide, C. neoformans causes 1 million cases of meningitis a year among HIV/AIDS patients, with nearly 625,000 deaths.

Thiele and colleagues focused on the interplay between C. neoformans in the lungs of mice and the host's immune system, which mount an immediate attack against the pathogen.

The immune response is led by macrophages, which circulate in the blood stream and engulf invading microbes to destroy them. The macrophages are essentially tiny torture chambers for pathogens, using hostile conditions and toxic substances to kill invaders.

Among the substances inside the macrophages is copper, a mineral the body needs for normal cognitive function and development, but also known to have antifungal properties. In the face of a pathogenic invasion of fungal spores, the macrophages begin concentrating more copper within their torture chamber as one of the body's antifungal weapons.

The Duke researchers found that lethal strains of C. neoformans have two ways of battling against the toxicity of the copper. First, the pathogen turns on genes that make proteins to protect it from copper toxicity, so even when exposed to the hostile copper environment in the macrophages, it survives.

But a second defense mechanism is also deployed. The fungus, sensing the copper-rich environment, triggers a response that shuts down the host's ability to pump more copper into the macrophages – defusing this weapon in the immune system's arsenal.

"With these two mechanisms, C. neoformans can defend itself by sequestering the copper, and somehow communicate to the host macrophage, commanding that it shut down the copper pumps," Thiele said.

Thiele said studies are now focusing on how antifungal agents might thwart the pathogen's two defense systems. "The detoxification machinery might represent an effective drug target," Thiele said.

In addition to Thiele, study authors include Chen Ding, Richard A. Festa, Ying-Lien Chen and Joseph Heitman from Duke; Anna Espart and Sílvia Atrian from Universitat de Barcelona, Spain; Òscar Palacios, Jordi Espín and Mercè Capdevila from Universitat Autònoma de Barcelona, Spain.

The work was supported in part by the National Institutes of Health (GM48140-24, 2P30 AI064518-06, AI50438).

Sarah Avery | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

A simple mechanism could have been decisive for the development of life

23.05.2018 | Life Sciences

Genetic diversity helps protect against disease

23.05.2018 | Life Sciences

Spinning rugby balls: The rotation of the most massive galaxies

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>