Resistance of Asian Cryptococcus neoformans Serotype A Is Confined to Few Microsatellite Genotypes

Contains fulltext : 109375.pdf (publisher's version ) (Open Access)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

Human cryptococcosis: relationship of environmental and clinical strains of Cryptococcus neoformans var. neoformans from urban and rural areas

Forty-five clinical and 55 environmental strains of Cryptococcus neoformans var. neoformans from Sao Paulo, Brazil, were tested for their susceptibilities to amphotericin B, fluconazole, itraconazole, and flucytosine by the broth microdilution method according to the National Committee of Clinical Laboratory Standards guidelines. Electrophoretic karyotypes analysis by counter-clamped homogeneous electrophoresis was used to compare their genetic relatedness. Molecular typing revealed three clinical profiles very similar to two environmental profiles and an identical environmental and clinical pro. le. The results showed that human cryptococcosis can be acquired from environmental strains, which had similar minimum inhibitory concentration values to clinical strains, for antifungal agents.159171