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

Microb Pathog. 2024 Dec 22:107255. doi: 10.1016/j.micpath.2024.107255. Online ahead of print.

Abstract

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.

Keywords: CO(2) sensing; Candida tropicalis; Rca1; carbonic anhydrase; filamentation.