Secreted lipases supply fatty acids for yeast growth in the absence of de novo fatty acid synthesis

The yeast Candida parapsilosis has emerged as a major human pathogen. The fungus is found in diverse environments as well as in different mammalian hosts, indicative of a successful adaptation to various niches. Fatty acids are the building blocks of cell membranes. Thus, the yeast must have evolved efficient ways to assimilate fatty acids from different sources, such as glucose via de novo fatty acid synthesis or lipids via lipolysis. We have recently shown that blocking the fatty acid synthesis pathway or interfering with the production of secreted lipases impeded yeast growth in glucose and lipid-containing media, respectively. However, in a more complex media (e.g., presence of glucose and lipids), blockage of either pathway individually resulted in growth similar to wild-type yeast. Here, we demonstrate that dual inhibition of these pathways significantly decreased yeast growth in complex media. Therefore, we propose that simultaneously targeting secreted lipases and fatty acid pathways might be ideal to combat C. parapsilosis disease, and perhaps other pathogenic fungi.