Re: Enzyme revealed that is key to fungus's ability to breach immune system

[Guest guest]

great find sharon, think this fits in with

it.

proton delivery in NO reduction by fungal nitric oxide reductase

http://www.jbc.org/cgi/content/full/275/7/4816

fusarium,nitric oxide

http://www.medscape.com/medline/abstract/12092813

plants physology

http://www.plantphysiol.org/cgi/content/abstract/139/2/991

a fungal vapor bioreactor used for removal of nitric oxide from waste

gas streams. this is amazeing, maybe all the uses for fungi is why

they really dont want to admit to the bad part.

http://www.medscape.com/medline/abstract/11417681

>

> I have never seen this study before. I was looking up information

on fungal

> nitric oxide when I came upon this. Nitric oxide appears to play

a key role

> in MCS. So does that mean fungal nitric oxide could be a key to

explaining

> MCS in mold victims?

>

> Sharon

>

> November 2003

>

> From _Duke University Medical Center_ (http://www.dukemednews.org/)

>

> Enzyme revealed that is key to fungus's ability to breach immune

system

>

> 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 Medical

Institute

> investigators at Duke University Medical Center.

> 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 ph Heitman, M.D.,

director

> of Duke's Center for Microbial Pathogenesis, and HHMI biochemist

> 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.,

,

> M.D., Limin Liu, Ph.D., and Nussbaum, all of Duke.

>

>

>