ArticleAntimicrobial agents and chemotherapy2009
Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 171 citations in OpenAlex.
- Antifungal Susceptibility Does Not Correlate With Fungal Clearance or Survival in AIDS-Associated Cryptococcal Meningitis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Parameters affecting the reliable measurement of fluconazole tolerance using disk diffusion assays withMicrobiology spectrum · 2026Article
- Beyond antifungal susceptibility: molecular mechanisms, detection, and clinical implications of fungal heteroresistance.Molecular biology reports · 2026Review
- Investigating the therapeutic potential of the antibacterial drug nitroxoline in combating cryptococcal infection.PLoS neglected tropical diseases · 2026Article
- Synergic Effect of Fluconazole and Quinoline Derivatives Combination AgainstMicroorganisms · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Review
- Target product profile and discovery and development path for novel cryptococcal disease treatments.The Journal of infection · 2025Review
- Antifungal persistence: Clinical relevance and mechanisms.PLoS pathogens · 2025Review
- Loss of theMicrobiology spectrum · 2025Article
- Investigation of voriconazole heteroresistance in clinical isolates ofMicrobiology spectrum · 2025Article
- Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B AgainstAntibiotics (Basel, Switzerland) · 2025Article
- A Cryptococcus neoformans polysaccharide conjugate vaccine made with filtered polysaccharide elicits protective immunity in mice.Fungal biology · 2025Article
- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
- The impact of phenotypic heterogeneity on fungal pathogenicity and drug resistance.FEMS microbiology reviews · 2025Review
- Antifungal Drug Resistance.Current topics in microbiology and immunology · 2025Review
- Fluconazole Resistance and Heteroresistance in Cryptococcus spp.: Mechanisms and Implications.Revista da Sociedade Brasileira de Medicina Tropical · 2025Review
- Improved Broad Spectrum Antifungal Drug Synergies with Cryptomycin, a Cdc50-Inspired Antifungal Peptide.ACS infectious diseases · 2024Article
- Antifungal heteroresistance causes prophylaxis failure and facilitates breakthrough Candida parapsilosis infections.Nature medicine · 2024Article
- Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans.Nature microbiology · 2024Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In 1999, heteroresistance to triazoles was reported in Cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis in an AIDS patient and in a diagnostic strain from a non-AIDS patient. In this study, we analyzed 130 strains of C. neoformans isolated from clinical and environmental sources before 1979, prior to the advent of triazoles, and 16 fluconazole (FLC)-resistant strains isolated from AIDS patients undergoing FLC maintenance therapy during 1990 to 2000. All strains isolated prior to 1979 manifested heteroresistance (subset of a population that grows in the presence of FLC) at concentrations between 4 and 64 microg/ml, and all 16 FLC-resistant AIDS isolates manifested heteroresistance at concentrations between 16 and 128 microg/ml. Upon exposure to stepwise increases in the concentration of FLC, subpopulations that could grow at higher concentrations emerged. Repeated transfer on drug-free media caused the highly resistant subpopulations to revert to the original level of heteroresistance. The reversion pattern fell into four categories based on the number of transfers required. The strains heteroresistant at > or =32 microg/ml were significantly more resistant to other xenobiotics and were also more virulent in mice than were those heteroresistant at < or =8 microg/ml. During FLC treatment of mice infected by strains with low levels of heteroresistance, subpopulations exhibiting higher levels of heteroresistance emerged after a certain period of time. The ABC transporter AFR1, known to efflux FLC, was unrelated to the heteroresistance mechanism. Our study showed that heteroresistance to azole is universal and suggests that heteroresistance contributes to relapse of cryptococcosis during azole maintenance therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.