FUNDED PROJECTS

Millions of microbial species live within or on the human body, most of them harmless and many even beneficial to human health. Among these are yeast species, which belong to the fungal kingdom. Candida albicans is a microscopic yeast commonly found in the intestines, the mouth and in the vagina. While it is usually benign, it occasionally overgrows, causing superficial infections commonly known as thrush. However, under some circumstances, this yeast may penetrate the intestinal barrier, causing infections of the blood or internal organs, which is defined as invasive candidiasis. Such life-threatening infections are commonly seen in healthcare environments, particularly in immunocompromised patients; mortality rates of invasive candidiasis can be as high as 25-50 percent, despite the use of currently available antifungal drugs.

Prof. Steffen Jung and his team recently discovered a novel strain of yeast, living quietly in our guts, that may be able to prevent invasive candidiasis. Like many scientific breakthroughs, this study began with a serendipitous finding. While investigating yeast infections, Prof. Jung and his team in the Department of Immunology and Regenerative Biology at the Weizmann Institute noticed that some of their laboratory mice could not be colonized with C. albicans, but instead carried a previously unknown species of yeast. Jung and his co-workers isolated the organism and found it was a new representative of the Kazachstania clade, a type of innocuous and harmless yeast widely used in sourdough preparation. The new yeast, which Jung named Kazachstania weizmannii, in honor of Dr. Chaim Weizmann, lives harmlessly in the intestines of mice and humans. In laboratory animals, Kazachstania weizmannii can displace the pathogenic Candida albicans yeast.

The studies to be performed in the MAVRI scheme aim to investigate the mechanism that underlies the robust competition between yeasts, first in test tubes and then in animals. To achieve this goal, Jung teamed up with Prof. Judith Berman, a renowned expert in Candida biology, at the Shmunis School of Biomedical and Cancer Research at Tel Aviv University. Together, the researchers will recapitulate the yeast competition, which so far has only been observed in the gut context. They will use laboratory cultures of yeast to enable the easy testing of many basic questions. In parallel, they will identify Candida variants that resist the K. weizmannii competition. This will allow them to define underlying genetic and molecular pathways that contribute to the ability of the pathogen and the beneficial yeasts to compete with one another. An in-depth understanding of this phenomenon has the potential to guide the development of new anti-fungal therapies, which are a critical unmet need in the clinic.