Geographically structured populations of Cryptococcus neoformans Variety grubii in Asia correlate with HIV status and show a clonal population structure

Kantarawee Khayhan, Ferry Hagen, Weihua Pan, Sitali Simwami, Matthew C Fisher, Retno Wahyuningsih, Arunaloke Chakrabarti, Anuradha Chowdhary, Reiko Ikeda, Saad J Taj-Aldeen, Ziauddin Khan, Margaret Ip, Darma Imran, Ridhawati Sjam, Pojana Sriburee, Wanqing Liao, Kunyaluk Chaicumpar, Varaporn Vuddhakul, Wieland Meyer, Luciana TrillesLeo J J van Iersel, Jacques F Meis, Corné H W Klaassen, Teun Boekhout*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.

Original languageEnglish
Article numbere72222
JournalPLoS ONE
Issue number9
Publication statusPublished - 2013
Externally publishedYes

Bibliographical note

This work was supported by a research grant from University of Phayao, Thailand ( FH was funded by the Odo van Vloten
Foundation, the Netherlands. WH was granted by the National Natural Science Foundation of China (no. 31270180) and the National Basic Research Program of
China (no. 2013CB531606). MCF was granted by the Wellcome Trust ( and the Biotechnology and Biological Sciences Research
Council, grant number BB/D52637X/1 ( TB and SJT were supported by a grant from the Qatar National Research Fund, grant number NPRP 5-
298-3-086. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


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