Therapy May Combat Fungal Infections, New Evidence Suggests

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Light Therapy May Combat Fungal Infections, New Evidence Suggests

28 Mar 2005

http://www.virtualmedicalcentre.com/news.asp?artid=6102

A newly discovered mechanism by which an infectious fungus perceives

light also plays an important role in its virulence, according to

Medical Institute investigators at Duke University

Medical Center. The findings suggest that changes in light following

fungal invasion of the human body may be an important and previously

overlooked cue that sparks infection, the researchers said.

The discovery in the human pathogen Cryptococcus neoformans further

suggests that light therapy, in combination with anti-fungal drug

treatments, might offer an effective method to combat a variety of

fungal infections, particularly those of the skin or nails, said

HHMI investigator ph Heitman, M.D., B. Duke professor of

molecular genetics and microbiology and medicine at Duke.

Light therapy is now used for medical conditions, such as seasonal

affective disorder. The most common method, called bright-light

therapy, requires that patients sit near a special light box fitted

with high-intensity, full-spectrum or white light bulbs. UV

irradiation is also used to repigment skin affected by the

autoimmune disorder vitiligo.

The findings also have important implications for understanding

early fungal evolution, Heitman and study lead author

Idnurm, Ph.D., reported in a forthcoming issue of Public Library of

Science Biology, published online March 15, 2005. The National

Institute for Allergy and Infectious Diseases and the Burroughs

Wellcome Fund supported the research.

The potentially life-threatening fungus C. neoformans invades the

central nervous system to cause disease, most commonly in patients

who lack a functioning immune system, such as organ transplant

recipients, those with HIV/AIDS, and patients treated with steroids

or cancer chemotherapy. The fungus' global importance as a health

threat has therefore risen in parallel with the increase in

immunosuppressive therapies and the worldwide HIV/AIDS epidemic.

Light normally inhibits mating of C. neoformans. The Duke team has

now identified two genes responsible for that light response. Loss

of the same genes also reduces fungal virulence in mice, they

reported.

Earlier studies had linked the genes to light-sensing in another

distantly related fungal lineage, an indication that the fungal

light sensor arose early in evolution and may be shared by many

extant fungal species. Other well-studied fungi, such as

Saccharomyces cerevisiae, or baker's yeast, have apparently lost

their ability to sense light, Heitman said, and have neither of the

conserved light-sensing proteins.

" Fungi have many negative implications for human life as they lead

to human disease, as well as plant disease and mold, " said Idnurm, a

post-doctoral fellow at Duke. " However, fungi also play important

beneficial roles, for example, as a source of food and

pharmaceuticals.

" Therefore, an understanding of the role of environmental signals

such as light in fungal development is vital to increase the

benefits and decrease the costs that fungi present. "

The researchers first tested the importance of genes with known

roles in light sensitivity of another, distantly related fungus.

Yeast strains lacking one of those genes, known as white collar 1

(BWC1), mated equally well in the light or the dark, implicating

that gene in the fungus' ability to sense light. BWC1 also functions

in the fungus' resistance to ultraviolet light, they reported.

Further study identified a second, related gene, BWC2, that is also

required for C. neoformans normal response to both blue and

ultraviolet light.

Moreover, the researchers found, mice inoculated with C. neoformans

lacking either of the light-sensing genes remained healthy 30 days

later, while those infected with the normal fungus died by day 30.

The finding points to novel virulence pathways, Heitman said, as the

BWC1 and BWC2 mutants were not impaired for any of the

characteristics previously linked to virulence.

" The genes required for light sensing, while not essential for

virulence, do contribute to the rapidity with which the fungus

causes lethal infection in the mammalian host, " Heitman said. " It is

therefore conceivable that light could be used as a therapy for

fungal infections, particularly infections at the body surface, such

as those of skin or nails. " Laser therapy might also be possible for

certain fungal sinus infections, he added.

The finding that Cryptococcus shares its light-sensing mechanism

with other distantly related fungi also has important implications

for understanding fungal evolution, Heitman said. The researchers

speculate that evolution of these light-sensing genes more than 400

million years ago may have had major significance for fungal

colonization of land, at a time when UV irradiation was particularly

intense.

(Source: Duke University Medical Center, March 2005)

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