Researchers find new regulator underlying C. albicans pathogen

Scientists have uncovered a previously unknown regulator that controls when Candida albicans switches from “white” to “opaque” cell types, according to a study published online January 26, 2016 in the journal mBio. This finding may eventually enable scientists to better combat yeast’s transition from a latent fungus to a pathogen, researchers said.

“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,” said lead author Aaron D. Hernday, PhD, Assistant Professor in the Department of Molecular and Cell Biology at the University of California Merced, in Merced, CA.

Unlike other fungal species, C. albicans possesses the uncommon ability to switch between two distinct heritable cell types—white and opaque—each of which has unique abilities to cause disease. White cells are more likely to lead to internal infections while opaque cells are better adapted for colonization of specific host niches, as with skin infections.

Previous research of C. albicans has described a group of transcriptional regulators that form a regulatory circuit underlying the switch between white and opaque cell types. One of these regulators, Wor1, is the only one that is absolutely required for the formation of opaque cells.

In this study, Dr. Hernday and colleagues identified a new transcriptional regulator of white-opaque switching, Ssn6, which is absolutely required for the maintenance of the white cell type.

Unlike the other known regulators, Ssn6 does not bind to DNA directly, but rather associates with specific combinations of the other regulators to control the switch. “Our results establish that Ssn6 represents a second layer of white-opaque switching regulation, where it represses genes through association with the previously described sequence-specific regulators,” the authors wrote.

Because the white to opaque switch occurs in only about 1 out of every 1,000 cell divisions, and because the opaque cells frequently switch back to white, researchers have had a difficult time trying to study the pathogen in the opaque form. But 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. Plus, the discovery could also make further advancements even easier to achieve.

For instance, when researchers deleted the Ssn6 gene, it inactivated the switching mechanism and “locked” cells into the opaque type.

“Although we currently understand some of the unique biological characteristics of the opaque cell type, there are many mysteries that remain unanswered,” Dr. 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.”