Same-sex mating by fungi spawned infection outbreak, evidence suggests

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Public release date: 9-Oct-2005

http://www.eurekalert.org/pub_releases/2005-10/dumc-smb100605.php

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Duke University Medical Center

Same-sex mating by fungi spawned infection outbreak, evidence

suggests

DURHAM, N.C. – Same-sex mating between two less harmful yeast

strains might have spawned an outbreak of disease among otherwise

healthy people and animals on Vancouver Island, British Columbia,

Medical Institute geneticists at Duke University

Medical Center have reported. The fungus, Cryptococcus gattii, is

normally restricted to the tropics and subtropics.

The researchers said their findings provide important additional

insight into the origin of the Vancouver Island outbreak, which

began in 1999. Moreover, the evidence that sex played an important

role in the pathogen's expansion may provide a useful model for the

evolution of infectious diseases and parasites more generally, they

said.

The team reported its findings October 9, 2005, in an advanced

online publication of Nature. The work was supported by the National

Institute of Allergy and Infectious Disease.

After extensive genetic analysis of fungal samples, the researchers

suggest that mating between two less harmful fungal strains of the

same sex or " mating type " produced the more virulent form. That

strain has now taken hold and appears to be spreading -- perhaps

driven by unique conditions in the Vancouver area, they said.

" While the number of people infected so far does not approach that

of many other infectious diseases, this fungus is invading the

central nervous systems of people who have no other apparent risk

factors except having taken a walk in the park on Vancouver Island, "

said ph Heitman, M.D., Ph.D. " A year after infection, some of

these people still have not fully recovered.

" The fungus appears to have become entrenched in the Vancouver

Island area, " he added. " It is unlikely to disappear, and all

indications are that it is spreading. Our findings suggest that sex

played a role in the expanded geographic range for this pathogen. "

Since it was first documented in 1999, C. gattii has infected at

least 100 people on Vancouver Island and the Canadian mainland and

led to four deaths. The fungus, which lives in trees and soil, has

also infected a variety of domestic and marine animals, including

dogs, cats, llamas and porpoises.

C. gattii is closely related to the more widespread infectious

yeast, Cryptococcus neoformans. The potentially life-threatening C.

neoformans invades the central nervous system to cause disease. It

most commonly affects immune-compromised patients such as organ

transplant recipients and cancer patients -- whose immune systems

are crippled by immunosuppressive drugs or chemotherapy -- and

people with HIV/AIDS. In contrast, C. gattii infects individuals

with apparently normal immunity. Symptoms include persistent

headaches, coughing and night sweats. In rare cases, C. gattii

causes cryptococcal disease, pneumonia, meningitis or death.

While C. neoformans is found worldwide in association with pigeon

droppings, the rarer C. gattii is normally restricted to tropical

and subtropical areas, often in association with Eucalyptus trees.

" It is suspected that the infectious propagules of Cryptococcus are

airborne spores, " Heitman said. " Such spores are produced during

sexual reproduction, though mating of the fungus has never been

observed in nature. "

In plants and animals, sexual identity is governed by sex

chromosomes, Heitman explained. In fungi, however, sexual identity

is determined by so-called " mating type loci, " genes arranged

contiguously, but which typically do not span an entire chromosome.

Cryptococcus exists in two mating types, " a " and " alpha, " determined

by a single genetic region, or locus.

Earlier studies by the Duke team found that most Vancouver Island

outbreak isolates are sexually fertile, but all are of one " sex, " a

trend that would seem to preclude the normal sexual cycle. A recent

laboratory study led by Heitman's group suggested a possible

explanation: the related yeast C. neoformans can undergo same-sex

mating between two alpha partners.

Among clinical and environmental isolates of the fungus from British

Columbia, the researchers identified two forms: an extremely

virulent major strain, which accounted for 95 percent of all

samples, and a less virulent and less common strain, which made up

the other five percent.

By comparing select gene sequences that spanned the genomes of the

Vancouver Island fungi to samples collected from around the world,

the team traced the rarer type to identical isolates in Australia.

The major form matched a sample taken from an infected person in

Seattle 30 years ago and another collected from a Eucalyptus tree in

San Francisco in 1992.

What's more, the Canadian strains shared approximately half of their

genetic makeup, suggesting that the two might be related. Further

analysis confirmed this initial finding, suggesting that the two C.

gattii strains in Vancouver Island are either siblings or that one

is the parent and the other the progeny.

" Given that the minor outbreak form also exists in multiple

locations in Australia, while the major outbreak form has only been

found in the Pacific Northwest, we favor the hypothesis that the

minor type represents one of two parental strains that gave rise to

the major outbreak isolate, " said study author Fraser, Ph.D.,

also of Duke. " The second parent strain remains to be discovered. "

Additional examination of the mating type locus provided evidence

that the major outbreak isolate may have resulted from same-sex

mating, Heitman added. In a traditional sexual cycle, all alpha

progeny inherit identical alpha genes from their alpha parent.

However, the mating type locus of the two strains from Vancouver

Island – both of the alpha mating type -- differed at numerous

sites, they found.

" Sex within the same mating-type may confer an evolutionary

advantage when the opposite mating type is unavailable, " Heitman

said. " Other human pathogens or parasites may harbor cryptic same-

sex cycles that contribute to produce progeny with altered

virulence, geographic or host range or other advantageous

characteristics. "

Collaborators on the study include Giles, Wenink,

Scarlett Geunes-Boyer, Jo Rae , Diezmann, Andria

, Stajich, Fred Dietrich and Perfect, all of Duke.

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