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

Khayhan K, Hagen F, Pan W, Simwami S, Fisher MC, Wahyuningsih R, Chakrabarti A, Chowdhary A, Ikeda R, Taj-Aldeen SJ, Khan Z, Ip M, Imran D, Sjam R, Sriburee P, Liao W, Chaicumpar K, Vuddhakul V, Meyer W, Trilles L, van Iersel LJ, Meis JF, Klaassen CH, Boekhout T - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Parasitology, Faculty of Medical Sciences, University of Phayao, Phayao, Thailand ; CBS-KNAW Fungal Biodiversity Centre, Department of Yeast and Basidiomycete Research, Utrecht, The Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

ABSTRACT
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.

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Population structure analysis among Asian C.neoformans var. grubii isolates obtained with the program STRUCTURE.(A) Comparing isolates from different countries and (B) global C. neoformans var. grubii isolates (data from http://mlst.mycologylab.org). The population groups are indicated by different colors. Each bar represents the individual isolates. Mixed color bar represents to share haplotypes in the individual isolate.
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pone-0072222-g005: Population structure analysis among Asian C.neoformans var. grubii isolates obtained with the program STRUCTURE.(A) Comparing isolates from different countries and (B) global C. neoformans var. grubii isolates (data from http://mlst.mycologylab.org). The population groups are indicated by different colors. Each bar represents the individual isolates. Mixed color bar represents to share haplotypes in the individual isolate.

Mentions: Clusters of Asian C. neoformans var. grubii populations were estimated using different numbers of populations that ranged from K = 2 to K = 10 using Structure. The Evanno method implemented in the Structure Harvester showed the highest delta K, an ad hoc statistic, was produced at K = 3 (Figure BA in Supplementary Figures S1). This implicates that K = 3 seems a good estimate for the actual number of populations included in this study, thus suggesting that three real genetic population clusters occur among the Asian C. neoformans var. grubii isolates that do not fully corroborate the geographically identified populations. The distribution of these three populations differed between the countries (Figure 5A). Almost all cryptococcal isolates from China, Hong Kong and Japan, as well as some isolates from Thailand, belonged to population I. The Thai and part of Indonesian isolates formed population II. Indian isolates, together with part of the Indonesian ones, formed the population III, whereas isolates from Kuwait and Qatar belonged to diverse populations containing genotypes from populations I-III (Figure 5A). Population structure analysis of the global C. neoformans var. grubii isolates showed five genetic populations (K = 5) (Figure BB in Supplementary Figures S1). The population structure of the Asian isolates was the same as described above, but two other major populations occurred, namely an African and North/South American population, and an European one. The African and American populations were genetically diverse. Some isolates contained haplotypes occurring among isolates from Asia and Europe and a few of the European isolates shared haplotypes that occurred in isolates from other continents (Figure 5B). However, whether these isolates represent acquisitions from the local environment, or are due to the patient traveling with an in situ latent infection is not known and requires further sampling of environmental isolates.


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

Khayhan K, Hagen F, Pan W, Simwami S, Fisher MC, Wahyuningsih R, Chakrabarti A, Chowdhary A, Ikeda R, Taj-Aldeen SJ, Khan Z, Ip M, Imran D, Sjam R, Sriburee P, Liao W, Chaicumpar K, Vuddhakul V, Meyer W, Trilles L, van Iersel LJ, Meis JF, Klaassen CH, Boekhout T - PLoS ONE (2013)

Population structure analysis among Asian C.neoformans var. grubii isolates obtained with the program STRUCTURE.(A) Comparing isolates from different countries and (B) global C. neoformans var. grubii isolates (data from http://mlst.mycologylab.org). The population groups are indicated by different colors. Each bar represents the individual isolates. Mixed color bar represents to share haplotypes in the individual isolate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760895&req=5

pone-0072222-g005: Population structure analysis among Asian C.neoformans var. grubii isolates obtained with the program STRUCTURE.(A) Comparing isolates from different countries and (B) global C. neoformans var. grubii isolates (data from http://mlst.mycologylab.org). The population groups are indicated by different colors. Each bar represents the individual isolates. Mixed color bar represents to share haplotypes in the individual isolate.
Mentions: Clusters of Asian C. neoformans var. grubii populations were estimated using different numbers of populations that ranged from K = 2 to K = 10 using Structure. The Evanno method implemented in the Structure Harvester showed the highest delta K, an ad hoc statistic, was produced at K = 3 (Figure BA in Supplementary Figures S1). This implicates that K = 3 seems a good estimate for the actual number of populations included in this study, thus suggesting that three real genetic population clusters occur among the Asian C. neoformans var. grubii isolates that do not fully corroborate the geographically identified populations. The distribution of these three populations differed between the countries (Figure 5A). Almost all cryptococcal isolates from China, Hong Kong and Japan, as well as some isolates from Thailand, belonged to population I. The Thai and part of Indonesian isolates formed population II. Indian isolates, together with part of the Indonesian ones, formed the population III, whereas isolates from Kuwait and Qatar belonged to diverse populations containing genotypes from populations I-III (Figure 5A). Population structure analysis of the global C. neoformans var. grubii isolates showed five genetic populations (K = 5) (Figure BB in Supplementary Figures S1). The population structure of the Asian isolates was the same as described above, but two other major populations occurred, namely an African and North/South American population, and an European one. The African and American populations were genetically diverse. Some isolates contained haplotypes occurring among isolates from Asia and Europe and a few of the European isolates shared haplotypes that occurred in isolates from other continents (Figure 5B). However, whether these isolates represent acquisitions from the local environment, or are due to the patient traveling with an in situ latent infection is not known and requires further sampling of environmental isolates.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Parasitology, Faculty of Medical Sciences, University of Phayao, Phayao, Thailand ; CBS-KNAW Fungal Biodiversity Centre, Department of Yeast and Basidiomycete Research, Utrecht, The Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus