Featured Research

from universities, journals, and other organizations

Enzyme Revealed That Is Key To Fungus's Ability To Breach Immune System

Date:
November 13, 2003
Source:
Duke University Medical Center
Summary:
A newly discovered mechanism by which an infectious fungus evades the immune system could lead to novel methods to fight the fungus and other disease-causing microbes, according to Howard Hughes Medical Institute investigators at Duke University Medical Center.

DURHAM, N.C. – A newly discovered mechanism by which an infectious fungus evades the immune system could lead to novel methods to fight the fungus and other disease-causing microbes, according to Howard Hughes Medical Institute investigators at Duke University Medical Center.

Related Articles


Disruption of a key enzyme in the fungus Cryptococcus neoformans – a common cause of infection of the central nervous system in patients such as organ transplant recipients who lack a functioning immune system -- led to a significant loss of fungal virulence in mice, the team found. That loss of virulence stemmed from the fungus's inability to launch a counterattack against components of the innate immune system, the body's first line of defense against infection, the study showed.

The Duke-based team -- led by HHMI geneticist Joseph Heitman, M.D., director of Duke's Center for Microbial Pathogenesis, and HHMI biochemist Jonathan Stamler, M.D. -- reported their findings in the Nov. 11, 2003, issue of Current Biology. The work was funded by the National Institutes of Allergy and Infectious Diseases and the Burroughs Wellcome Fund.

The "fungal defense" enzyme, called flavohemoglobin, is prevalent among many bacterial and fungal pathogens, Heitman said, which suggests that the findings in Cryptococcus are likely relevant to other infectious microbes. New drugs that target these enzymes might therefore represent effective treatments for a wide range of infectious diseases, he said.

The human immune system uses a two-pronged mechanism to fight infection: a rapid innate response and a slower adaptive response that depends on the production of antibodies. Key components of the innate immune system are "search-and-destroy" cells called macrophages that engulf and kill invading pathogens. Macrophages kill infectious microbes using a combination of oxidants, including hydrogen peroxide, nitric oxide and related molecules.

"The body must rely on macrophages of the innate immune system to protect itself before the adaptive immune system can respond to invasion," Heitman said. "While much is known about how pathogens defend themselves against hydrogen peroxide produced by the macrophages, this study is the first biologically relevant test of what microbes do to counteract nitric oxide and promote infection."

The researchers found that a mutant C. neoformans strain lacking the flavohemoglobin enzyme failed to break down nitric oxide in laboratory cultures. Fungus with the enzyme deficiency also ceased to grow when in the presence of nitric oxide, whereas ordinary fungus survived normally.

Mice infected with the flavohemoglobin-deficient C. neoformans survived for five days longer than those infected with the normally virulent strain. In contrast, the normal and mutant fungal strains were equally virulent in mice whose immune cells could not produce nitric oxide, the team reported.

The mutant fungus also failed to grow normally in laboratory dishes containing macrophage cells, further implicating the innate immune system in the loss of virulence exhibited by fungi lacking flavohemoglobin.

The team discovered a second enzyme, known as GSNO reductase, which also plays a role in defending the fungus against nitric oxide-related molecules produced by macrophages. Mutant fungal strains deficient in both enzymes were more severely impaired than those lacking flavohemoglobin only.

"By disabling either the fungal nitric oxide defense system or the immune system's ability to produce nitric oxide, we were able to tip the balance one way or the other – in favor of the fungal infection or the host," Heitman said. "That raises the possibility that we could treat infectious disease with drugs that either inhibit fungal defense enzymes or increase the innate immune system's ability to mount a nitrosative attack."

Collaborators on the study include Marisol de Jesus-Berrios, Ph.D., Gary Cox, M.D., Limin Liu, Ph.D., and Jesse Nussbaum, all of Duke.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Enzyme Revealed That Is Key To Fungus's Ability To Breach Immune System." ScienceDaily. ScienceDaily, 13 November 2003. <www.sciencedaily.com/releases/2003/11/031113070056.htm>.
Duke University Medical Center. (2003, November 13). Enzyme Revealed That Is Key To Fungus's Ability To Breach Immune System. ScienceDaily. Retrieved February 1, 2015 from www.sciencedaily.com/releases/2003/11/031113070056.htm
Duke University Medical Center. "Enzyme Revealed That Is Key To Fungus's Ability To Breach Immune System." ScienceDaily. www.sciencedaily.com/releases/2003/11/031113070056.htm (accessed February 1, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, February 1, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Hikers Rescued After Fall from Oregon Mountain

Hikers Rescued After Fall from Oregon Mountain

AP (Feb. 1, 2015) Two climbers who were hurt in a fall on Mount Hood are now being treated for their injuries. Rescue officials say they were airlifted off the mountain Saturday afternoon by an Oregon National Guard helicopter. (Feb. 2) Video provided by AP
Powered by NewsLook.com
Smart Glasses Augment Reality to Help Visually Impaired

Smart Glasses Augment Reality to Help Visually Impaired

Reuters - Innovations Video Online (Feb. 1, 2015) New augmented reality smart glasses developed by researchers at Oxford University can help people with visual impairments improve their vision by providing depth-based feedback, allowing users to "see" better. Joel Flynn reports. Video provided by Reuters
Powered by NewsLook.com
Flu Season Hitting Elderly Hard

Flu Season Hitting Elderly Hard

Reuters - US Online Video (Jan. 31, 2015) The CDC says this year&apos;s flu season is hitting people 65 years of age and older especially hard. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
CDC: Get Vaccinated for Measles

CDC: Get Vaccinated for Measles

Reuters - US Online Video (Jan. 30, 2015) The CDC is urging people to get vaccinated for measles amid an outbreak that began at Disneyland and has now infected more than 90 people. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins