Last But Not Yeast: Helen Murphy studies pathogenic progression in yeast cells

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ADITHI RAMAKRISHNAN / THE FLAT HAT

The number-one cause of fungal infections in humans is related to a single-celled baking ingredient. Helen Murphy, an assistant professor in the biology department, is currently using one to study the other.

Leading infection source Candida albicans is a species of yeast and a microbe — microscopic organism — that can have dangerous effects if inserted into the bloodstream. One of the simplest ways it gets there is by attaching itself to medical equipment.

Candida albicans has been found on pretty much every medical device that has been inserted into the body,” Murphy said. “You can get a systemic infection when you actually have the yeast inside you.”

Candida albicans can’t adhere to plastic equipment by themselves, according to Murphy: yeast cells form groups called biofilms that work together to attach to a surface and survive as a unit.

“The cells excrete something called an extracellular matrix that they can all attach to, and then there’s differentiation within the actual community; some cells are protecting the biofilm from environmental stress, some of them are helping the community be attached to a surface,” Murphy said. “As an evolutionary biologist, I’m really interested in the cooperation and cheating and all the dynamics within these communities.”

Murphy explained that since Candida albicans is challenging to study in a lab setting, she models yeast evolution in a close relative known as Saccharomyces cerevisiae. This single-celled yeast species grows quickly, can be stored easily and serves as a useful model for evolution.

“Most of the things people think about when they think about living organisms are eukaryotes, so those are your animals, your plants, your fungi…”, Murphy said. “Yeast is a eukaryotic cell, so it’s really representative of the kind of evolution that many of us think about in eukaryotes.”

Murphy stated that yeast cells replicate quickly, resulting in 50 generations over a period of two weeks. Over hundreds of replications, Murphy aims to evolve in the yeast the ability to attach to plastic surfaces. This trait gives virulent strains the ability to stick to medical equipment like catheters or implants and cause infections when the equipment contacts the human body. In clinics and hospitals, this effect is more pronounced and can lead to diseases that are harder for modern medicines to crack.

“When an organism infects the body or attaches to a surface, it becomes much more resistant to antimicrobials or antifungals, and this is just something it’s evolved to do to survive in a harsh world,” Murphy said. “But when it happens in a medical setting, it becomes much harder to get rid of an infection, in part because the cells are sort of cooperating with each other and they’re protected from the environment in that way.”

Murphy evolves plastic attachment in the yeast by growing the cells in glass tubes and placing a plastic bead in the tube. Due to natural variation, some of the yeast cells will have mutations in their genetic material that give them the ability to adhere to the plastic material, and some will not. After two days of growth, Murphy removes the bead and washes it with sterile water to remove any cells that are not strongly attached. The cells remaining on the bead have the ability to stick strongly to plastic and will pass this trait on to future generations when they divide. 

The yeast cells attached to the bead are removed using sound waves and placed in a new glass tube with a new plastic bead, so that they can continue to evolve over subsequent generations. Murphy has repeated this process for somewhere between 500 and 600 generations. The goal of this repetition is more than creating yeast cells that can attach to plastic surfaces, however; it is about finding out what makes yeast cells go from neutral to virulent, and what evolved traits give them the power to do so. 

“How does a microbe go from being a happy microbe that lives on you or near you to something that’s pathogenic?” Murphy said. “We’ve begun to ask, what are the traits that have come along with plastic adherence?”

Murphy explained that there are very few microbes whose only job is to infect the human body. Several of the most dangerous pathogens are ones that start off with no effect but acquire mutations throughout their life cycles that allow them to adapt to new conditions, group together on biofilms and mount successful attacks on humans.

“Asking the question of what makes something that’s not normally pathogenic, pathogenic, is far more relevant to human health than only studying something that can live in the human body,” Murphy said. “What’s much more dangerous, when you think about it, is all the microbes that could become pathogens when they get the right mutations.”

Murphy has identified certain behaviors that yeast cells have evolved along with the ability to stick to plastic. The next step in her evolution experiment is to see if the evolved yeast cells can be dangerous. 

“We’re about to start injecting wax moth larvae with our yeast to see if they’re, sort of, more killer,” Murphy said.

The yeast cells’ virulence is the final piece in Murphy’s years of Saccharomyces cerevisiae study. She wants to compile the research into two papers and submit them for publication in the spring. Murphy hopes that her study of microbial communities via yeast cells will inform the medical field, as well as debunk the theory that microbes exist in isolation. 

“People used to think of microbes as these individual cells living in the environment and duking it out with other microbes in the environment, but that’s not true,” Murphy said. “It turns out, there’s a lot of sociality within microbes.”