Decoding Cryptococcus: From African biodiversity to worldwide prevalence

Abstract

Fungal pathogens cause millions of infections and deaths annually, while also contributing to global food insecurity [1]. Among them, basidiomycete Cryptococcus species—particularly C. neoformans (Cn; previously C. neoformans var. grubii, serotype A; lineages VNI, VNII, VNBI, and VNBII), C. deneoformans (Cd; previously C. neoformans var. neoformans, serotype D; lineage VNIV), and the C. gattii (Cg) species complex (Fig 1A)—are significant opportunistic and primary pathogens, especially in sub-Saharan Africa [2,3]. These pathogens primarily cause cryptococcosis, manifesting as severe pulmonary infections or life-threatening meningoencephalitis in both immunocompromised and apparently immunocompetent individuals. Exposures are typically thought to occur by inhalation of desiccated yeast cells or spores from the environment [4]. While Cryptococcus species vary in their occurrence worldwide, mounting evidence suggests an evolutionary origin in Africa for most of the pathogenic Cryptococcus species, where they occupy diverse ecological niches such as trees, pigeon guano, and mammalian middens (Fig 1B). While Cn, Cd, and Cg are pathogenic, nonpathogenic species within the genus (such as C. amylolentus, C. wingfieldii, and C. floricola; Fig 1A) occur either as African microendemic species or are known thus far from only a single isolate in the Canary Islands (C. floricola) [5,6]. This review explores the likely African origins of Cryptococcus, its ecological diversity, and how pathogenic species spread globally, transitioning from environmental microbes to human pathogens.