Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans

Cryptococcus neoformans( C. neoformansvar. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformansfrom HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformansreveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub- cladesof the C. neoformansVNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub- cladesaccount for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub- clade, the most common sub- cladein Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype.