Population Genetic Analyses Reveal the African Origin and Strain Variation of Cryptococcus neoformans var. grubii

Cryptococcus neoformans is a ubiquitous, saprobic yeast and the cause of life-threatening infections. Humans acquire the infection by inhaling airborne cells from the environment. In the lungs, these cells become encapsulated yeasts and proliferate. In people with healthy immune responses, the infection may resolve or remain latent and subsequently cause disease. However, in immunocompromised people, such as HIV/AIDS patients, and less often in healthy hosts, the yeasts can disseminate to almost any part of the body; however, they are neurotropic, and meningoencephalitis is the most frequent and deadliest clinical manifestation [1–3]. An estimated 1 million new infections are acquired each year, and the majority of these cases occur in sub-Saharan Africa, which has the highest prevalence of patients with HIV/ AIDS [4]. In this region, C. neoformans is the most common cause of meningitis, and mortality hovers around 50%. Others who succumb to cryptococcosis are apparently immunocompetent and exhibit no evidence of underlying disease. For example, 71% of cryptococcal infections in China occur in people without pre-existing conditions [5]. There are two varieties, C. neoformans var. grubii (Cng) and C. neoformans var. neoformans (Cnn), which are distinguishable by molecular markers or their capsular serotypes, A or D, respectively. Diploid AD hybrids also occur in the environment and patients [6–8]. In addition, a sibling species, Cryptococcus gattii, causes similar infections. However, isolates of both serotype D and AD hybrids, as well as C. gattii, are much less common. At least 90% of human cryptococcal disease and fatalities are caused by Cng (serotype A) [9–11].