Ecology

Cryptococcus neoformans

Fluconazole

Microbiology

Biology

Gene

Cryptococcal meningitis

Ploidy

Antifungal

Viral disease

Meningitis

Resistance (ecology)

Surgery

Immunology

Cryptococcosis

Human immunodeficiency virus (HIV)

Genetics

Medicine

Journal of Clinical Investigation

BACKGROUND. Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) — a resistant subpopulation within a susceptible strain — is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans.

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis