The human gastrointestinal (GI) tract hosts a diverse microbiome comprising of bacteria, viruses and fungi within complex bionetworks and dynamic microenvironments (1). Here microbes, fundamental to host digestion and metabolism of dietary macronutrients, coexist and compete for nutrients to survive (1). Of the many metabolite bi-products generated by microbes involved in these processes, short chain fatty acids (SCFAs) are known to impact both host and microbial physiology (2). The yeast Candida albicans is a commensal microbe of the GI tract which can also cause superficial to severe systemic disease (3). It’s ability to morphologically transition from a yeast to a pathogenic hyphal form is correlated with its clinical manifestation (3).
We investigate the signalling pathways influenced by the metabolism of SCFAs, and how they affect gene expression via histone acylation and hyphal morphogenesis of C. albicans. We show that the SCFA crotonate, which causes the posttranslational modification of lysine crotonylation of histones and other proteins, represses hyphal morphogenesis of C. albicans in immune cell macrophages and in media mimicking the phagosomal environments. It also reduces hyphae-dependent macrophage killing by C. albicans. Furthermore, RNAseq analysis showed that crotonate upregulates fatty acid metabolic process and inhibits the expression of hyphal genes needed to drive pathogenicity in C. albicans. Our data suggests that crotonate acts in concert with hyphal transcriptional repressors to regulate hyphal morphogenesis. Collectively, these studies should shed light on the impact of SCFAs on C. albicans invasive hyphal morphogenesis and how it influences pathogenicity and virulence.