PRM1 Influences Mating and Virulence in Cryptococcus neoformans

Cryptococcus neoformans, an opportunistic pathogen, relies on homeostasis, environmental stability, and adaptability for its growth and survival. C. neoformans primarily infects immunocompromised individuals, increasing the propensity of invading the central nervous system. The most affected are individuals with HIV/AIDs. Recently, the World Health Organization classified C. neoformans as a Critical Priority fungal pathogen due to its widespread presence and high mortality rate. The ability to adapt to changes in environmental pH is one of the key factors contributing to C. neoformans pathogenicity. The gene CNAG_05866 was recently identified by researchers at Duke University via a mutagenesis screen to identify genes involved in pH adaptation. CNAG_05866, an ortholog of PRM1 in S. cerevisiae, is also important for pH adaptation. PRM1 in S. cerevisiae is known to play a role in plasma membrane fusion and mating. In this study, we deleted the PRM1 gene in C. neoformans and analyzed its impact on pH adaptation. Our findings show that the prm1Δ mutant exhibits significantly impaired growth at alkaline pH. Additionally, qPCR data suggest that PRM1 may act as a repressor of the SRE1 pH regulatory pathway. Furthermore, PRM1 influences mating and basidiospore production in C. neoformans, our data however suggests that it does not affect cell fusion during mating as the different prm1∆ crosses produce mating hyphae, making it different from the ortholog in S. cerevisiae.