Scientists ID Common Pathogen’s Weak Spot

Molecular biologists at Rice University have discovered a key defense mechanism that the yeast Candida albicans uses against attack by the human immune system.

This chink in the armor of Candida, the most common human fungal pathogen, could be exploited with new drugs for both lethal and nonlethal Candida outbreaks, including vaginal yeast infections and thrush.

Scientists estimate that 70 percent of people have Candida colonies in their intestines or mouths or on their skin. In most cases, the organism does not harm people, even though it depends on them for food. However, colonies of Candida sometimes grow too large, as happens in the case of yeast infections. Vaginal yeast infections are a common and painful problem for a significant percentage of women. The oral form of Candida infection, known as thrush, is a common problem for infants.

While such infections are usually not life-threatening, they can be deadly for some people, such as those who are HIV-positive or undergoing certain types of treatment for cancer. In cases where Candida infections spread to the bloodstream, mortality rates climb as high as 50 percent.

Human immune cells give off nitric oxide (NO) to slow the growth of yeast colonies, and the researchers ran side-by-side comparisons of Candida and baker’s yeast, an organism that doesn’t typically infect humans, to find the genes that Candida uses to protect itself against NO. They discovered that Candida, unlike baker’s yeast, is able to sense the presence of NO and ramp up its defenses. They now are trying to determine which chemical signals Candida uses to detect the presence of NO.

“Baker’s yeast and Candida both have the gene to make NO-scavenging enzymes, but Candida has three copies, and it alone has a mechanism to react to increased NO levels by producing more NO-scavengers,” says lead researcher Michael Gustin, associate professor of biochemistry and cell biology. “If we can identify the signaling mechanism it uses, that would give us one more useful target for new drug therapies.”

Gustin’s group is interested in learning whether other fungal pathogens, such as Aspergillus, a deadlier species than Candida, use the same NO defense. Gustin says Aspergillus has two genes that are good candidates for study, and he plans to begin research on them in the fall.
The research was supported by the National Science Foundation. Co-authors of the study, which was published in the journal Eukaryotic Cell, include Breanna Ullmann, Hadley Myers, Wiriya Chiranand, Qiang Zhao, and Luis Vega, all of Rice; Anna Lazzell and Jose Lopez-Ribot of the University of Texas Health Science Center at San Antonio; and Paul Gardner of Children’s Hospital Medical Center in Cincinnati.

—Jade Boyd