TY - JOUR
T1 - Resistance of Asian Cryptococcus neoformans serotype a is confined to few microsatellite genotypes
AU - Pan, Weihua
AU - Khayhan, Kantarawee
AU - Hagen, Ferry
AU - Wahyuningsih, Retno
AU - Chakrabarti, Arunaloke
AU - Chowdhary, Anuradha
AU - Ikeda, Reiko
AU - Taj-Aldeen, Saad J.
AU - Khan, Ziauddin
AU - Imran, Darma
AU - Sjam, Ridhawati
AU - Sriburee, Pojana
AU - Liao, Wanqing
AU - Chaicumpar, Kunyaluk
AU - Ingviya, Natnicha
AU - Mouton, Johan W.
AU - Curfs-Breuker, Ilse
AU - Boekhout, Teun
AU - Meis, Jacques F.
AU - Klaassen, Corné H.W.
N1 - Funding Information:
JFM has been a consultant to Astellas, Basilea, Merck and Schering-Plough and received speaker's fees from Gilead, Janssen Pharmaceutica, Merck, Pfizer, and Schering-Plough. CHK received a grant from Pfizer. RW is currently receiving a grant from IIR-Pfizer for doing research on Cryptococcus. RW is a speaker for Pfizer and Astellas Pharma. All other authors: no potential conflicts of interest relating to employment, consultancy, patents, products in development or marketed products. The sponsors of the research played no decision-making role in the design, execution, analysis and reporting of the research. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
PY - 2012/3/13
Y1 - 2012/3/13
N2 - Background: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries. Methodology/Principal Findings: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17. Conclusions: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine.
AB - Background: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries. Methodology/Principal Findings: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17. Conclusions: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine.
UR - http://www.scopus.com/inward/record.url?scp=84858111081&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0032868
DO - 10.1371/journal.pone.0032868
M3 - Article
C2 - 22427900
AN - SCOPUS:84858111081
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 3
M1 - e32868
ER -