All yeasts are not created equal. One is used to make bread and wine, while the other one shows up in the form of an infection called Candida albicans, better known as a yeast infection.
A group of Canadian researchers set out to study the difference between the two and found that yeast in bread is less similar to the one that causes the fungus.
The study published in Current Biology led by Concordia University Prof. Malcolm Whiteway, Ph.D., hopes to shine new light on what makes the pathogen tick and eventually help create targeted drugs to treat the ailment.
“From other research previously done in our lab, we had found that the regulation of gene expression in related circuits could be surprisingly different, so we looked for more examples of this,” Whiteway told R&D Magazine in an exclusive interview.
The bad yeast
Candida albicans is a type of yeast that causes fairly benign infections in people with strong immune systems. But to those suffering from AIDS or undergoing chemotherapy or transplants of organs or bone marrow—it can be a serious threat.
“Blood-stream infections related to Candida are frequently fatal,” Whiteway said in a statement
The professor and Tier 1 Canada Research Chair in Microbial Genomics conducted this study with key collaborators Walters Tebung, a Ph.D. candidate at Concordia and Joachim Morschhauser with Germany’s Institut für Molekulare Infektionsbiologie.
Since the fungus’ cells function very similarly to human cells, the antibiotics that have been greatly successful in treating bacterial infections are not active against them, while current anti-fungal drugs can have serious side-effects. This is why Whiteway’s research is aimed at helping the development of a new generation of anti-fungal drugs with minimal side effects, he said.
Ying-yang yeast
The research team examined how a cellular process in Candida albicans differs from the one in Saccharomyces cerevisiae—the yeast used to make bread and wine. Turns out that through “genetic rewiring,” the protein controlling a particular process in one yeast species controls something different in the other.
“The study involved proteins called transcription factors. These proteins bind DNA at specific sequences and control the expression of genes. We used a tool called Chip-chip to ask where a particular transcription factor called Ppr1 bound, we used a tool called transcription profiling to see if the bound genes were regulated, and computer analysis to see if the bound and regulated genes had a common function in the cell,” Whiteway told R&D. “We saw that the genes that were bound and regulated by Ppr1 in S. cerevisiae were very different from the genes bound and regulated in C. albicans.”
In other words, the rewiring occurs in a protein named Ppr1. In Candida albicans, this protein controls the degrading of purines—molecules that make up DNA. But the Ppr1 protein in Saccharomyces cerevisiae controls the building of pyrimidines—molecules that make up the elements of DNA complementary to purines.
“We learned that the two yeasts use the Ppr1 protein to regulate different things, and we propose that the switch in function occurred because the bakers’ yeast selected a lifestyle that allowed it to live in environments that were oxygen poor,” Whiteway added.
New drug-development option
Unveiling the differences between bread-making and disease-causing yeasts gives us a picture of how cells can be remarkably different even when they look familiar, according to the study. This is poignant from a drug development standpoint. Currently, it’s common practice to use Saccharomyces to produce drugs against Candida.
According to Whiteway, the study proves that the pathogen itself needs to be studied and not just the proxies, which leads to the assumption that the drugs which treat one will also treat the other. He hopes this study will one day lead to new treatment options for patients suffering with yeast infections with the goal of faster healing and reduction of suffering.
“It is very unlikely that eating bread or drinking wine will increase the risk of Candida infection. In general, most North Americans are already colonized with C. albicans, but the balance of your microbiota and your innate immune system keep things under control,” Whiteway concluded. “A yeast infection is not the result of C. albicans coming from the environment and causing an infection, it is more likely that something disturbs the immune system, or microbiota balance and the Candida are already present and get a chance to proliferate.”
