ArticleVirulence2018
Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus.
Article in Virulence, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
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- Pathogenic Fungal Sensing and Responses to Stressful Host Environments.Annual review of microbiology · 2025Review
- Deletion ofmSphere · 2025Article
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- Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae.Communications biology · 2024Article
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- Virulence perspective genomic research unlocks the secrets ofFrontiers in plant science · 2024Article
- Combination of gallium citrate and levofloxacin induces a distinct metabolome profile and enhances growth inhibition of multidrug-resistantFrontiers in microbiology · 2024Article
- Fungal siderophore metabolism with a focus on Aspergillus fumigatus: impact on biotic interactions and potential translational applications.Essays in biochemistry · 2023Article
- Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome.Nature communications · 2023Article
- Uncovering Phytotoxic Compounds Produced byJournal of fungi (Basel, Switzerland) · 2023Article
- A putative terpene cyclase gene (Frontiers in microbiology · 2023Article
- Therapeutic Target Identification and Inhibitor Screening against Riboflavin Synthase of Colorectal Cancer AssociatedCancers · 2022Article
- Sulfur Metabolism as a Promising Source of New Antifungal Targets.Journal of fungi (Basel, Switzerland) · 2022Review
- Functional Portrait of Irf1 (Orf19.217), a Regulator of Morphogenesis and Iron Homeostasis inFrontiers in cellular and infection microbiology · 2022Article
- Riboflavin as a promising antimicrobial agent? A multi-perspective review.Current research in microbial sciences · 2022Review
- Genomic and Metabolomic Analyses of the Marine FungusJournal of fungi (Basel, Switzerland) · 2021Article
- Review
- Inducible Selectable Marker Genes to ImproveJournal of fungi (Basel, Switzerland) · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAspergillus fumigatus is the most prevalent airborne fungal pathogen, causing invasive fungal infections mainly in immunosuppressed individuals. Death rates from invasive aspergillosis remain high because of limited treatment options and increasing antifungal resistance. The aim of this study was to identify key fungal-specific genes participating in vitamin B biosynthesis in A. fumigatus. Because these genes are absent in humans they can serve as possible novel targets for antifungal drug development.
methodsBy sequence homology we identified, deleted and analysed four key A. fumigatus genes (riboB, panA, pyroA, thiB) involved respectively in the biosynthesis of riboflavin (vitamin B2), pantothenic acid (vitamin B5), pyridoxine (vitamin B6) and thiamine (vitamin B1).
resultsDeletion of riboB, panA, pyroA or thiB resulted in respective vitamin auxotrophy. Lack of riboflavin and pantothenic acid biosynthesis perturbed many cellular processes including iron homeostasis. Virulence in murine pulmonary and systemic models of infection was severely attenuated following deletion of riboB and panA, strongly reduced after pyroA deletion and weakly attenuated after thiB deletion.
conclusionsThis study reveals the biosynthetic pathways of the vitamins riboflavin and pantothenic acid as attractive targets for novel antifungal therapy. Moreover, the virulence studies with auxotrophic mutants serve to identify the availability of nutrients to pathogens in host niches. ABBREVIATIONS: BPS: bathophenanthrolinedisulfonate; BSA: bovine serum albumin; CFU: colony forming unit; -Fe: iron starvation; +Fe: iron sufficiency; hFe: high iron; NRPSs: nonribosomal peptide synthetases; PKSs: polyketide synthaseses; wt: wild type.
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