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Lab explores implications of fungal sex

Researchers look at existence of sexual reproduction in Candida yeasts

In a laboratory on the fifth floor of the Biomedical Center, a group of University researchers carefully observes sexual acts that have never before been witnessed by humans.

Associate Professor of Biology Richard Bennett investigates the sexual cycle of Candida yeasts, a group of unicellular fungi notorious for infecting humans. In the last two months, he and his colleagues have published two papers that detail aspects of sexuality in Candida species. The lab is dedicated to exploring Candida biology, but Bennett says there is an additional motivation to his research on fungal sex: It may help humans fight infection.

Candida pose little threat to healthy humans — they often reside in people’s guts. But when the immune system is impaired or the yeasts move into places where they are not supposed to be, they can cause serious infection. Stephen Jones GS, a doctoral student in the Bennett Lab, said Candida infection is an acute issue in hospitals because the patients have weakened immune systems. While visiting the hospital for one condition, patients can develop an infection if hospital surfaces are infested with the fungus.

“Secondary (Candida) infections end up being more deadly than the initial condition they came into the clinic for,” Jones said.

When Bennett began studying Candida yeast, virtually every species in the group was classified as completely asexual. Scientists simply never observed them having sex —  reproducing by exchanging genetic information. Instead, these fungi were thought to reproduce exclusively by producing identical copies of themselves through a process called budding.

Fourteen years ago, a lab in which Bennett worked was the first group to observe sex in Candida albicans. Bennett eventually formed his own lab, and continues to debunk the notion of Candida asexuality.

“The more and more we study these species, the more we find examples of species that have the ability to do sex,” Bennett said. He now suspects that most Candida species can reproduce by swapping genetic material.

Mating often occurs in “sexual biofilms,” mat-like Candida communities bound to a surface. These outgrowths show up on hospital appliances and can be difficult to eradicate, as they adhere firmly to the material. Jones, who investigates sexual biofilm formation, compared the communities to a “club,” where “social lubrication” leads to mating. But in sexual biofilms, sexual pheromones take the place of alcohol as the social lubricant.

Mating occurs when two yeasts send out projections from their cell body, which fuse and form a sort of bridge through which genetic information is transferred.

Maintaining the machinery necessary for sex requires energy and can be costly for yeasts. Bennett said he believes there must be some benefit to maintaining the ability to have sex under certain conditions.

He detailed these benefits of sex in a review article published this month in the journal Nature. Candida infections are often found in the mouth or skin of humans, where they face a hostile environment. The yeasts must withstand the human immune system and antifungal treatment to grow. To survive, they must adapt. Occasional sexual reproduction, which shuffles genes and gives rise to new combinations, may be beneficial to the yeast, as it allows Candida to quickly evolve in response to a host’s defenses.

“In general, sexual reproduction is a way to adapt to a changing environment,” Bennett said.

Joseph Heitman, director of the Center for Microbial Pathogenesis at Duke University, said understanding yeast sexual reproduction “is likely central … to the development of drug resistance against widely used antifungal drugs.” He added that Bennett and Jones’ review “covers a very broad view of the field.”

Bennett said his lab’s theory regarding the benefits of fungal sex fits what scientists have observed so far, but the picture of fungal sex is still emerging. He noted that Jones examined the mechanisms of sex in a species believed to be asexual just two years ago in a different paper this year.

Bennett also said he was interested in looking at how fungal sex plays out inside our bodies, rather than in a petri dish. “We know a lot about it in vitro. … We know a lot less about where this happens in humans.”

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