Figuring out the Fungi That Live on and Inside Us

Recent progress in our understanding of Malassezia fungi is helping to unlock the secrets of their role in human health and disease.

microbiome

Although the microbiome has been linked to everything from diabetes to mental health, most studies to date have focused on bacteria, and to a lesser extent, viruses. Much less is known about the impact of fungi, an entire kingdom of life distinct from animals, plants and bacteria. In particular, scarce information is available about a group of fungi called Malassezia, although millions can be found on every human being.

“Fungi are much harder to study than bacteria for many reasons—they are fastidious in culture, slow growing, possess more complex biology and genetics, and so on. Hence, understanding of fungi has seriously lagged that of other microbial fields,” said Thomas Dawson, Senior Principal Investigator at the Skin Research Institute of Singapore (SRIS), adding that “Malassezia represent one of the most difficult fungi to study.”

While Malassezia colonize human skin with ease, it was difficult to culture these fungi in the lab until scientists discovered that they required lipid supplementation. Moreover, not just any lipid would do. “We found that Malassezia cannot utilize unsaturated fatty acids, as they lack the enzyme Δ-9 desaturase,” Dawson said.

On the skin, Malassezia take up saturated fatty acids and leave behind unsaturated fatty acids such as oleic and palmitoleic acid, which are irritating and likely cause seborrhoeic dermatitis. Indeed, numerous members of the Malassezia genus appear to be involved in various inflammatory conditions. “Most researchers see Malassezia globosa as a key player in dandruff and seborrhoeic dermatitis, and Malassezia sympodialis as a key factor in atopic eczema. Recent work has also implicated Malassezia restricta in Crohn’s disease and irritable bowel disease,” Dawson said.

Conditions caused by Malassezia are generally treated with broad-spectrum antifungal compounds, particularly azoles. However, the widespread use of azoles in both medical and agricultural applications also led to antifungal resistance and treatment failure.

In a bid to reduce reliance on azoles, researchers are now working on identifying more specific targets in Malassezia that would be less likely to induce broad-spectrum drug resistance. These targets include enzymes that Malassezia produce to obtain nutrients.

The complex biochemical and immune signaling between Malassezia and the human host also remains poorly understood. “Future research will involve examining this signaling in the hopes of identifying materials which can hijack the system and either decrease Malassezia numbers or instruct them to behave differently and promote health instead of disease,” Dawson said.

The A*STAR-affiliated researcher contributing to this research is from the Skin Research Institute of Singapore (SRIS).