Long Chain Fatty Acids Promote Candida albicans Gut Colonization by Restructuring the Fungal Cell Surface

Musfirat Shubaita, BS (Advisor: J. Christian Perez, PhD)
 

          The yeast Candida albicans is a facultative anaerobe residing in the human digestive tract. Although fungal genetic determinants of mammalian host colonization have been identified, little is known about signals and molecules in the intestinal environment influencing C. albicans proliferation. Previous unpublished data from the Perez lab showed that oleic acid, one of the most abundant long-chain fatty acids in nature, promotes C. albicans colonization of the murine intestine. The goal of this research is to determine how oleic acid contributes to C. albicans gut colonization. I hypothesized that oleic acid promotes, either directly or indirectly, the expression of C. albicans molecules that facilitate the persistence of this fungus in the intestinal domain. I found that β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. albicans to colonize the high-oleic acid diet-fed mice. Transcriptome analysis revealed that, under anaerobic conditions, oleic acid promoted expression of several C. albicans transcription factors which are known to positively regulate intestinal colonization. Furthermore, oleic acid induced expression of a variety of adhesins and cell surface components. Finally, I identified SOK1 as an oleic acid-induced kinase that dictates cell wall mannan exposure and binding to intestinal mucin under anaerobic conditions. Taken together, these findings indicate that in environments largely void of oxygen (like the colon), dietary oleic acid promotes a C. albicans cell surface configuration that enhances gut occupation.

Advisory Committee:

• J. Christian Perez, PhD, Chair
• Anne Marie Krachler, PhD
• Michael Lorenz, PhD
• Jyotika Sharma, PhD
• Chenggang Wu, PhD

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