Abstract
Cryptococcus neoformans is a basidiomycete human fungal pathogen causing lethal meningoencephalitis, mainly in immunocompromised patients. Oxidoreductases are a class of enzymes that catalyze redox, playing a crucial role in biochemical reactions. In this study, we identified one Cryptococcus oxidoreductase-like protein-encoding gene OLP1 and investigated its role in the sexual reproduction and virulence of C. neoformans. Gene expression patterns analysis showed that the OLP1 gene was expressed in each developmental stage of Cryptococcus, and the Olp1 protein was located in the cytoplasm of Cryptococcus cells. Although it produced normal major virulence factors such as melanin and capsule, the olp1Δ mutants showed growth defects on the yeast extract peptone dextrose (YPD) medium supplemented with lithium chloride (LiCl) and 5-fluorocytosine (5-FC). The fungal mating analysis showed that Olp1 is also essential for fungal sexual reproduction, as olp1Δ mutants show significant defects in hyphae growth and basidiospores production during bisexual reproduction. The fungal nuclei imaging showed that during the bilateral mating of olp1Δ mutants, the nuclei failed to undergo meiosis after fusion in the basidia, indicating that Olp1 is crucial for regulating meiosis during mating. Moreover, Olp1 was also found to be required for fungal virulence in C. neoformans, as the olp1Δ mutants showed significant virulence attenuation in a murine inhalation model. In conclusion, our results showed that the oxidoreductase-like protein Olp1 is required for both fungal sexual reproduction and virulence in C. neoformans.
Highlights
Cryptococcus neoformans is a globally distributed fungal pathogen causing life-threatening cryptococcal meningitis in both immunocompromised and immunocompetent patients [1]
Our results suggest that Olp1 regulates sexual reproduction and fungal virulence in C. neoformans
These results suggested that the Olp1 protein might be an oxidoreductases-like protein
Summary
Cryptococcus neoformans is a globally distributed fungal pathogen causing life-threatening cryptococcal meningitis in both immunocompromised and immunocompetent patients [1]. As an important human fungal pathogen, C. neoformans has three classical virulence factors: capsule formation, melanin production, and growth at 37 ◦C [11,12]. Other virulence factors such as urease [13], extracellular phospholipase activity [14], mannitol production [15,16], laccase [17], hyaluronic acid [18], calcineurin [19], and metalloprotease [20,21] contribute to the infection and the pathogenesis of C. neoformans. Our results suggest that Olp regulates sexual reproduction and fungal virulence in C. neoformans
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