ArticleAntimicrobial agents and chemotherapy2011
Azole resistance of Aspergillus fumigatus biofilms is partly associated with efflux pump activity.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Guideline
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- Genetic analysis of common triazole resistance mechanisms in a collection ofAntimicrobial agents and chemotherapy · 2025Article
- Fungal biofilms in human health and disease.Nature reviews. Microbiology · 2025Review
- Accelerating the understanding ofCurrent research in microbial sciences · 2024Review
- Phase-Dependent Differential In Vitro and Ex Vivo Susceptibility ofJournal of fungi (Basel, Switzerland) · 2023Article
- Mitochondrial Inner Membrane ABC Transporter Bcmdl1 Is Involved in Conidial Germination, Virulence, and Resistance to Anilinopyrimidine Fungicides in Botrytis cinerea.Microbiology spectrum · 2023Article
- Afu-Emi1 Contributes to Stress Adaptation and Voriconazole Susceptibility in Aspergillus fumigatus.Microbiology spectrum · 2023Article
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- Lipid-Like Biofilm from a Clinical Brain Isolate of Aspergillus terreus: Quantification, Structural Characterization and Stages of the Formation Cycle.Mycopathologia · 2023Article
- Transport across Membranes: Techniques for Measuring Efflux in Fungal Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study investigated the phase-dependent expression and activity of efflux pumps in Aspergillus fumigatus treated with voriconazole. Fourteen strains were shown to become increasingly resistant in the 12-h (16- to 128-fold) and 24-h (>512-fold) phases compared to 8-h germlings. An Ala-Nap uptake assay demonstrated a significant increase in efflux pump activity in the 12-h and 24-h phases (P<0.0001). The efflux pump activity of the 8-h germling cells was also significantly induced by voriconazole (P<0.001) after 24 h of treatment. Inhibition of efflux pump activity with the competitive substrate MC-207,110 reduced the voriconazole MIC values for the A. fumigatus germling cells by 2- to 8-fold. Quantitative expression analysis of AfuMDR4 mRNA transcripts showed a phase-dependent increase as the mycelial complexity increased, which was coincidental with a strain-dependent increase in azole resistance. Voriconazole also significantly induced this in a time-dependent manner (P<0.001). Finally, an in vivo mouse biofilm model was used to evaluate efflux pump expression, and it was shown that AfuMDR4 was constitutively expressed and significantly induced by treatment with voriconazole after 24 h (P<0.01). Our results demonstrate that efflux pumps are expressed in complex A. fumigatus biofilm populations and that this contributes to azole resistance. Moreover, voriconazole treatment induces efflux pump expression. Collectively, these data may provide evidence for azole treatment failures in clinical cases of aspergillosis.
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