ArticleInfection and immunity2006
Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans.
Article in Infection and immunity, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 119 citations in OpenAlex.
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- Proteomic Analysis Revealed that DVL, a Lectin Purified fromACS omega · 2025Article
- Disruption of the ATP-dependent unfoldase ClpX reverses antifungal resistance in Cryptococcus neoformans.Nature communications · 2025Article
- Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.PLoS biology · 2025Article
- Antifungal Resistance in Cryptococcal Infections.Pathogens (Basel, Switzerland) · 2024Review
- Quantitative analysis of septin Cdc10 & Cdc3-associated proteome during stress response in the fungal pathogen Cryptococcus neoformans.PloS one · 2024Article
- Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence ofFrontiers in cellular and infection microbiology · 2024Article
- The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi.Microorganisms · 2023Review
- Resolving the Temporal Splenic Proteome during Fungal Infection for Discovery of Putative Dual Perspective Biomarker Signatures.Journal of the American Society for Mass Spectrometry · 2023Article
- Methods for Antifungal Susceptibility Testing of theJournal of fungi (Basel, Switzerland) · 2023Review
- Searching for new antifungals for the treatment of cryptococcosis.Revista da Sociedade Brasileira de Medicina Tropical · 2023Review
- Comprehensive whole genome sequencing with hybrid assembly of multi-drug resistantCurrent research in microbial sciences · 2023Article
- From environmental adaptation to host survival: Attributes that mediate pathogenicity ofVirulence · 2022Article
- Gene expression profiles of ERG11, MDR1 and AFR1 in Cryptococcus neoformans var.grubbi from HIV patientsBiomedica : revista del Instituto Nacional de Salud · 2022Article
- Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Novel ABC Transporter Associated with Fluconazole Resistance in Aging ofJournal of fungi (Basel, Switzerland) · 2022Article
- The Combination of Iron and Copper Increases Pathogenicity and Induces Proteins Related to the Main Virulence Factors in Clinical Isolates ofJournal of fungi (Basel, Switzerland) · 2022Article
- The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.Drugs · 2021Review
- The need for environmental surveillance to understand the ecology, epidemiology and impact of Cryptococcus infection in Africa.FEMS microbiology ecology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently demonstrated that upregulation of the ATP binding cassette (ABC) transporter-encoding gene AFR1 in Cryptococcus neoformans is involved in the in vitro resistance to fluconazole of this yeast. In the present study, we investigated the role of AFR1 in the in vivo response to fluconazole in a mouse model of systemic cryptococcosis. Mice were infected with a wild-type fluconazole-susceptible strain of C. neoformans, strain BPY22; an afr1 mutant, BPY444, which displayed hypersusceptibility to fluconazole in vitro; or an AFR1-overexpressing strain, BPY445, which exhibited in vitro resistance to the drug. In each of the three groups, infected animals were randomly assigned to fluconazole treatment or untreated-control subgroups. As expected, fluconazole prolonged survival and reduced fungal tissue burdens (compared with no treatment) in BPY22- and BPY444-infected mice, whereas it had no significant effects in mice infected with BPY445. When the pathogenicities of these strains in mice were investigated, strain BPY445 was significantly more virulent than BPY22 following inhalational or intravenous inoculation, but mice infected with BPY444 survived significantly longer than BPY22-infected animals only when infection was acquired via the respiratory tract. In in vitro macrophage infection studies, strain BPY445 also displayed enhanced intracellular survival compared with strains BPY22 and BPY444, suggesting that its increased virulence may be due to its reduced vulnerability to the antimicrobial factors produced by phagocytic cells. These findings indicate that the upregulation of the AFR1 gene is an important factor in either determining the in vivo resistance to fluconazole or influencing the virulence of C. neoformans.
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