ArticlePloS one2016
Mitochondrial Complex I Is a Global Regulator of Secondary Metabolism, Virulence and Azole Sensitivity in Fungi.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Directed evolution of the pathogenic moldAntimicrobial agents and chemotherapy · 2026Article
- Genome-wide discovery and phenotyping of non-coding transcripts in A. fumigatus reveals lncRNAs with a role in antifungal drug sensitivity.Nature communications · 2026Article
- Six-month surveillance ofFrontiers in cellular and infection microbiology · 2026Article
- The 24-kDa subunit of mitochondrial complex I regulates growth, microsclerotia development, stress tolerance, and virulence in Verticillium dahliae.BMC biology · 2024Article
- Genomic factors shape carbon and nitrogen metabolic niche breadth across Saccharomycotina yeasts.Science (New York, N.Y.) · 2024Article
- Drug-ResistantPathogens (Basel, Switzerland) · 2023Review
- Genomic and ecological factors shaping specialism and generalism across an entire subphylum.bioRxiv : the preprint server for biology · 2023Article
- Mitochondrial Membrane-Associated Protein Mba1 Confers Antifungal Resistance by Affecting the Production of Reactive Oxygen Species in Aspergillus fumigatus.Antimicrobial agents and chemotherapy · 2023Article
- AfLaeA, a Global Regulator of Mycelial Growth, Chlamydospore Production, Pathogenicity, Secondary Metabolism, and Energy Metabolism in the Nematode-Trapping FungusMicrobiology spectrum · 2023Article
- Extensive non-coding sequence divergence between the major human pathogenFrontiers in fungal biology · 2022Article
- Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity inFrontiers in microbiology · 2022Article
- Identification of Novel Mutations Contributing to Azole Tolerance of Aspergillus fumigatus throughAntimicrobial agents and chemotherapy · 2021Article
- Genome-Wide Association Analysis for Triazole Resistance inPathogens (Basel, Switzerland) · 2021Article
- Article
- Shared evolutionary footprints suggest mitochondrial oxidative damage underlies multiple complex I losses in fungi.Open biology · 2021Article
- Mechanisms of triazole resistance in Aspergillus fumigatus.Environmental microbiology · 2020Review
- The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2020Review
- Linking calcium signaling and mitochondrial function in fungal drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Differentially Regulated Transcription Factors and ABC Transporters in a Mitochondrial Dynamics Mutant Can Alter Azole Susceptibility ofFrontiers in microbiology · 2020Article
- Aspergillus fumigatus and Aspergillosis in 2019.Clinical microbiology reviews · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent estimates of the global burden of fungal disease suggest that that their incidence has been drastically underestimated and that mortality may rival that of malaria or tuberculosis. Azoles are the principal class of antifungal drug and the only available oral treatment for fungal disease. Recent occurrence and increase in azole resistance is a major concern worldwide. Known azole resistance mechanisms include over-expression of efflux pumps and mutation of the gene encoding the target protein cyp51a, however, for one of the most important fungal pathogens of humans, Aspergillus fumigatus, much of the observed azole resistance does not appear to involve such mechanisms. Here we present evidence that azole resistance in A. fumigatus can arise through mutation of components of mitochondrial complex I. Gene deletions of the 29.9KD subunit of this complex are azole resistant, less virulent and exhibit dysregulation of secondary metabolite gene clusters in a manner analogous to deletion mutants of the secondary metabolism regulator, LaeA. Additionally we observe that a mutation leading to an E180D amino acid change in the 29.9 KD subunit is strongly associated with clinical azole resistant A. fumigatus isolates. Evidence presented in this paper suggests that complex I may play a role in the hypoxic response and that one possible mechanism for cell death during azole treatment is a dysfunctional hypoxic response that may be restored by dysregulation of complex I. Both deletion of the 29.9 KD subunit of complex I and azole treatment alone profoundly change expression of gene clusters involved in secondary metabolism and immunotoxin production raising potential concerns about long term azole therapy.
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