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

P. M. Ashton, L. T. Thanh, P. H. Trieu, D. Anh, N. M. Trinh, J. Beardsley, F. Kibengo, W. Chierakul, D. A. B. Dance, S. Rattanavong, V. Davong, L. Q. Hung, N. V. V. Chau, N. L. N. Tung, A. K. Chan, G. E. Thwaites, D. G. Lalloo, C. Anscombe, L. T. H. Nhat, J. Perfect, G. Dougan, S. Baker, S. Harris and J. N. Day ()
Additional contact information
P. M. Ashton: Oxford University Clinical Research Unit
L. T. Thanh: Oxford University Clinical Research Unit
P. H. Trieu: Oxford University Clinical Research Unit
D. Anh: Oxford University Clinical Research Unit
N. M. Trinh: Oxford University Clinical Research Unit
J. Beardsley: Oxford University Clinical Research Unit
F. Kibengo: MRC/UVRI and LSHTM Uganda Research Unit
W. Chierakul: Mahidol Oxford Tropical Medicine Research Unit
D. A. B. Dance: University of Oxford
S. Rattanavong: Lao–Oxford–Mahosot Hospital–Wellcome Trust Research Unit
V. Davong: Lao–Oxford–Mahosot Hospital–Wellcome Trust Research Unit
L. Q. Hung: Cho Ray Hospital
N. V. V. Chau: Hospital for Tropical Diseases
N. L. N. Tung: Hospital for Tropical Diseases
A. K. Chan: University of Toronto
G. E. Thwaites: Oxford University Clinical Research Unit
D. G. Lalloo: Liverpool School of Tropical Medicine
C. Anscombe: Oxford University Clinical Research Unit
L. T. H. Nhat: Oxford University Clinical Research Unit
J. Perfect: Duke University
G. Dougan: Wellcome Trust-Cambridge Centre for Global Health Research
S. Baker: Oxford University Clinical Research Unit
S. Harris: The Wellcome Trust Sanger Institute
J. N. Day: Oxford University Clinical Research Unit

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals 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-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account 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-clade in 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.

Date: 2019
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DOI: 10.1038/s41467-019-10092-5

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