title: Azole heteroresistance in Cryptococcus neoformans: emergence of resistant clones with chromosomal disomy in the mouse brain during fluconazole treatment.
abstract: We have previously reported that Cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clones in vivo was unrelated to the strain's MIC to fluconazole.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Sionov
authors.forename: Yun C
authors.initials: YC
authors.lastname: Chang
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000235:genetics; D003453:Cryptococcosis / Q000188:drug therapy / Q000235:genetics; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D025141:Drug Resistance, Fungal / Q000235:genetics; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D015725:Fluconazole