Exploring the Genetics of Candida albicans

A microscopy photo of Candida albicans shows the cells escaping mammalian macrophages, used by the immune system to fight infections. Kristin McCue studies a protein complex in Candida that is required for growth of this infectious organism. Photo by Erika Kroger.  

 

A University of Arkansas postdoctoral researcher has received funding from the American Heart Association to study the genetics of a fungus that has the potential to kill people when they are most vulnerable after organ transplants.

Kristin McCue, a researcher in biological sciences in the J. William Fulbright College of Arts and Sciences, received $85,000 over two years to study the genetics of Candida albicans, a fungus commonly known for causing vaginal yeast infections in women, certain types of skin infections and diaper rash. In addition, it can also cause life-threatening infections in its systemic form, which can happen in hospitals, particularly with patients who have undergone organ transplants or other major surgery.

This disease can travel through the blood stream and infect internal organs, McCue said. The American Heart Association funds basic research into blood diseases, such as McCues project.

By examining the properties of specific genes in the organism, McCue and biological sciences professor David McNabb hope to find ways to retard the growth of Candida, or render it more susceptible to antifungal medications. This could lead to better therapies for the infection.

The researchers have focused on a complex of four proteins within the organism. This complex is required for the binding of DNA without it, the organism could not replicate or grow. One of the proteins in this complex has two different genes that code for it an unusual trait.

We suspect that different conditions turn on the different genes, McCue said. Im trying to see which gene is needed under which conditions.

To do this, McCue has engineered two different Candida strains, one where she deleted one of the genes that codes for this protein, and one where she deleted the other gene and kept the first one. Then she is growing the two strains under different conditions, one of which is under high and low iron conditions. The organism lives in both low iron conditions in the gut, and high iron conditions in the blood.

One of the strains with a deleted gene grew poorly in the low iron environment, indicating that this gene is necessary in low iron conditions.

The question now is, can it switch from expressing one gene to expressing the other gene in extremely low iron conditions? McCue said. Even though these are separate genes, they still appear to work together.

McCue is also examining the genetically different organisms under different amounts of sugar and nitrogen, and at different levels of acidity. This is important, since Candida appears to flourish in very different types of environments, and the protein expression could be an underlying cause.

It is starting to come out that there are other yeast organisms that have multiple genes for these same four proteins, McCue said. These organisms seem to be the norm, while Saccharomyces, the yeast used to make breads and has only one gene coding for this protein, may be the exception. Its important to know how it is different and why it is different from Saccharomyces, she said. We want to find out if this difference is part of why Candida albicans can become pathogenic.

Source: University of Arkansas