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Nat Commun. 2019 May 2;10(1):2035. doi: 10.1038/s41467-019-10092-5.

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

Author information

1
Wellcome Trust Asia Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Ho Chi Minh City, Vietnam.
2
Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
3
Marie Bashir Institute, University of Sydney, Sydney, 2050, NSW, Australia.
4
MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.
5
Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
6
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.
7
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
8
Cho Ray Hospital, Ho Chi Minh City, Vietnam.
9
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
10
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, M4N 3M5, ON, Canada.
11
Dignitas International, Zomba, Malawi.
12
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
13
Department of Medicine and Department of Molecular Genetics and Microbiology, Division of Infectious Diseases, Duke University, Durham, NC, 27710, USA.
14
Wellcome Trust-Cambridge Centre for Global Health Research, Cambridge, CB2 0XY, UK.
15
Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, Cambridgeshire, UK.
16
Department of Medicine, University of Cambridge, Cambridge, CB2 0SP, UK.
17
Wellcome Trust Asia Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Ho Chi Minh City, Vietnam. jday@oucru.org.
18
Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK. jday@oucru.org.

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.

PMID:
31048698
PMCID:
PMC6497710
DOI:
10.1038/s41467-019-10092-5
[Indexed for MEDLINE]
Free PMC Article

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