Gluconate Kinase Is Required for Gluconate Assimilation and Sporulation in Cryptococcus neoformans

• Published in: Microbiology spectrum 2022-04, Vol.10 (2), p.e0030122
• Main Authors: Jezewski, Andrew J, Beattie, Sarah R, Alden, Katy M, Krysan, Damian J
• Format: Article
• Language: English
• Subjects: carbon dioxide; Cryptococcosis; Cryptococcus neoformans; Cryptococcus neoformans - genetics; gluconate kinase; Gluconates; Humans; metabolism; Mycology; Phosphotransferases (Alcohol Group Acceptor); Research Article
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.00301-22

Cryptococcus neoformans is an environmental yeast and an opportunistic human pathogen. The ability to cause disease depends on the ability to adapt to the human host. Previous studies implicated nfectivity- elated inase ( , CNAG_03048) as required for establishing an infection. We genetically and biochemically characterized as a gluconate kinase and propose the name . This metabolic enzyme utilizes gluconate to produce 6-phosphogluconate as part of the alternative oxidative phase of the pentose phosphate pathway (AOXPPP). The presence of confirms that the AOXPPP is present and able to compensate for loss of the traditional OXPPP, providing an explanation for its nonessentiality. C. neoformans can utilize gluconate as an alternative carbon source in a -dependent manner. In our efforts to understand the role of in host adaptation and virulence, we found that -deficient mutants have variable virulence and carbon dioxide tolerance across multiple strains, suggesting that second site mutations frequently interact with deletion mutations. In our effort to isolate these genetic loci by backcrossing experiments, we discovered that deficient strains are unable to sporulate. These data suggest that gluconate metabolism is critical for sporulation of C. neoformans. Cryptococcus neoformans is a fungal pathogen that contributes to nearly 180,000 deaths annually. We characterized a gene named that appears to interact with other genetic loci involved with the ability of C. neoformans to act as a pathogen. While these interacting genetic loci remain elusive, we discovered that plays roles in both metabolism and mating/sporulation. Further interrogation of the mechanistic role for in sexual reproduction may uncover a larger network of genes that are important for host adaptation and virulence.