Carbon dioxide suppresses filamentous growth in the human fungal pathogen Candida tropicalis

A striking characteristic of the human fungal pathogen Candida albicans is its ability to switch between budding yeast morphology and the filamentous form, facilitating its adaptation to changing host environments. The filamentous growth of C. albicans is mediated by various environmental factors, such as carbon dioxide (CO₂), N-acetylglucosamine (GlcNAc), serum, and high temperature. Despite extensive studies in C. albicans, the regulatory mechanism of filamentation in Candida tropicalis, a fungal species that is closely related to C. albicans, has not been well characterized. In this study, we reveal opposite roles of CO₂ in regulating filamentation among Candida species: CO₂ promotes filamentous growth in C. albicans and Candida dubliniensis, whereas it inhibits filamentation in C. tropicalis. Despite the critical role of the canonical cAMP pathway in filamentation, it is dispensable in CO₂-regulated filamentation in C. tropicalis. A CO₂-specific signaling is involved in the regulation of filamentous growth in C. tropicalis. Additionally, we identify two key elements involved in CO₂ sensing in C. tropicalis: a single carbonic anhydrase (CA) Nce103 and the bZIP transcription factor Rca1. Both Nce103 and Rca1 are important for cellular growth in ambient air and negatively regulate filamentous development in response to CO₂ in C. tropicalis. These findings reveal a distinct mechanism underlying CO₂-regulated filamentation in C. tropicalis, contributing to a deeper understanding of its unique survival strategies in diverse environmental niches and providing new insights into the adaptive evolution of CO₂ sensing mechanisms among various fungal pathogens.