Cryptococcus neoformans

Past decades opportunistic fungal infections, which are mainly caused by Candida, Cryptococcus, and Aspergillus species, have been a major health-care problem worldwide due to the dramatically increased number of immunocompromised patients having AIDS, solid-organ transplant, and anticancer-chemotherapy. Among them, C. neoformans is widely distributed worldwide in natural environments, including soil, tree, water, animals, and bird droppings, and can be infected into humans by inhalation into the lung alveoli. C. neoformans serotype A strains (C. neoformans var. grubii) are most commonly isolated worldwide, causing fungal pneumonia and meningitis.

C. neoformans is haploid with a bipolar mating system that contains two opposite mating-types, a and α and a single mating locus defines each mating type. C. neoformans has two different sexual cycles. One is bisexual mating response between two opposite mating-partner, a and α. When a and α strains co-exist under certain environment, such as nutrient starvation, each mating type cell secretes pheromone to trigger cell-cell fusion and filamentous growth. Another is a homothallic unisexual cycle, which is called monokaryotic fruiting (same-sex mating). Monokaryotic fruiting readily occurs in serotype D strains and used to be considered as the mitotic and asexual process. However, several lines of evidence demonstrated that genetic recombination and ploidy change take place during same-sex mating, which indicates that monokaryotic mating is an alternative sexual response originated from α cells.

C. neoformans has several virulence factors: antiphagocytic polysaccharide capsule, antioxidant melanin, and urease. Cryptococcus capsule mainly consists of glucuronoxylomannan (GXM) and glucuronoxylomannangalactan (GXMGal). GXM and GXMGal account for about 90% and 10%, respectively of total polysaccharide capsule. Capsule prevents C. neoformans from being dehydrated and phagocytosed by macrophage. Melanin is a dark, brown pigment and a negatively charged, insoluble molecule. Melanin is produced when cells are grown in media containing phenolic compounds. Melanized cells are more resistant to oxidative stress and ultraviolet irradiation than non-melanized cells. Furthermore, melanin is involved in debilitating the host defense mechanism during infection as a virulence factor. Urease catalyzes the hydrolysis of urea to ammonia and carbamate. Urease has a critical role in fungal dissemination to the brain and causing meningoencephalitis.

Outside Links

1. C. neoformans genome databases
     Serotype A (Duke University)      Serotype A (Broad Institute)      Serotype D JEC21

     Serotype D B3501      BAC fingerprint mapping of C. neoformans      Cryptococcal Working Group

2. Bahnlab Website
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