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Researchers Find Key to Harmful Pathogen’s Transformation

January 26, 2016

Aaron HerndayA team of scientists led by UC Merced Professor Aaron D. Hernday has made a major advancement in understanding how the most common fungal pathogen in humans can alter its cellular phenotype and behavior.

Although typically a benign component of the human microbiome, Candida albicans can transition into a dangerous pathogen that can cause yeast infections in women, thrush in babies, and serious bloodstream infections in people with compromised immune systems. The researchers have discovered a transcriptional regulator that controls the cell’s switch from “white” to “opaque” cell types, each of which has unique abilities to cause disease.

Hernday and his team published their findings today (Jan. 26) in the journal mBio. He said the breakthrough will make it easier to study the cells in both their white and opaque states and could eventually enable scientists to better combat the transition from latent fungus to pathogen.

I often refer to the white-opaque switch as generating two distinct pathogens from a single genome,” Hernday said. “It’s similar to the way cells in our skin, bone, muscle and other tissues take on different identities even though they all contain the same genetic information.

The discovery of this regulator sheds new light on our understanding of the complex transcriptional network that controls this change in C. albicans, and also provides a valuable tool for understanding how it causes disease.”

Discovery Could Benefit Future Studies

In his previous work, Hernday identified several transcriptional regulators — proteins that bind to DNA and control which genes are turned on or off — that help control the transition from white to opaque in C. albicans. Of these regulators, Wor1 is the only one that is absolutely required for the formation of opaque cells.

Hernday’s new study identifies a new regulator, Ssn6, which is absolutely required for the maintenance of the white cell type. Ssn6 does not bind to DNA directly, but rather associates with specific combinations of the other regulators to control the switch.

The identification of Ssn6 as a key regulator of a genetic switch that leads to disease in humans will enable scientists to better combat those diseases — and the discovery could also make further advancements even easier to achieve. The switch from white to opaque occurs in only about one out of every thousand cell divisions, and the opaque cells frequently switch back to white, which has made it difficult to study the pathogen in the opaque form.

Although we currently understand some of the unique biological characteristics of the opaque cell type, there are many mysteries that remain unanswered,” Hernday said. “By being able to force the cells into one type or the other, we can more easily study the characteristics of each cell type.”

Hernday, a professor with the School of Natural Sciences and the Health Sciences Research Institute, conducted the study with UC Merced Professor Clarissa J. Nobile and undergraduate student Clement N. Laksana, along with UC San Francisco researchers Matthew B. Lohse, Liron Noiman and Alexander D. Johnson.

Nobile, who is on the cutting edge of the growing field of biofilms, last year became the first UC Merced researcher to earn a Pew scholar award.