CryptoADAPT: Cryptococcus Adaptation to causing human Disease in Africa through Pathogen Thermotolerance

Yeasts in the Cryptococcus species complex (mainly C. neoformans and C. gattii), are significant opportunistic primary pathogens, especially in sub- Saharan Africa where they principally cause a life-threatening meningoencephalitis. Mounting evidence suggests an evolutionary origin in Africa for pathogenic as well as non-pathogenic species (such as C. amylolentus, C. wingfieldii, and C. floricola) which occur as microendemic species. Yet, we have very little understanding of the true diversity of Cryptococcus in Africa, and even less understanding of how species adapt in the face of strong directional selection presented by extremes of temperature or environmental change. We propose a multidisciplinary programme that combines ecology, experimental evolution, genomics and fungal biology to better understand human exposures to Cryptococcus across African biodiversity hotspots. We have shown the existence of pathogenic ‘staging grounds’ where pathogenicity can potentially evolve in hosts such as insects, birds and small mammals. Further evidence has shown that exposure to high temperatures can trigger rapid evolution that is generated by, for instance, activation of transposons. Our project will train early-career researchers across three African countries and will leverage state-of-the-art genomic and phenotypic platforms in the UK and USA to understand the triggers for adaptation across this key fungal genus.