title: Resistance of Asian Cryptococcus neoformans serotype A is confined to few microsatellite genotypes.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Institute of Dermatology and Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China. panweihua@medmail.com.cn
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.forename: Kantarawee
authors.initials: K
authors.lastname: Khayhan
authors.forename: Ferry
authors.initials: F
authors.lastname: Hagen
authors.forename: Retno
authors.initials: R
authors.lastname: Wahyuningsih
authors.forename: Arunaloke
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chowdhary
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikeda
authors.forename: Saad J
authors.initials: SJ
authors.lastname: Taj-Aldeen
authors.forename: Ziauddin
authors.initials: Z
authors.lastname: Khan
authors.forename: Darma
authors.initials: D
authors.lastname: Imran
authors.forename: Ridhawati
authors.initials: R
authors.lastname: Sjam
authors.forename: Pojana
authors.initials: P
authors.lastname: Sriburee
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liao
authors.forename: Kunyaluk
authors.initials: K
authors.lastname: Chaicumpar
authors.forename: Natnicha
authors.initials: N
authors.lastname: Ingviya
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.forename: Ilse
authors.initials: I
authors.lastname: Curfs-Breuker
authors.forename: Teun
authors.initials: T
authors.lastname: Boekhout
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.forename: Corné H W
authors.initials: CH
authors.lastname: Klaassen
mesh_terms: D001208:Asia; D003455:Cryptococcus neoformans / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole; D005437:Flucytosine; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D012703:Serotyping
chemical_list: D015725:Fluconazole; D005437:Flucytosine