ArticleInfection and immunity2011
Targeted disruption of nonribosomal peptide synthetase pes3 augments the virulence of Aspergillus fumigatus.
Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Opportunistic pathogenicity in fungi can transcend species boundaries.bioRxiv : the preprint server for biology · 2026Article
- Aneuploidy promotes transient stress adaptation and metabolic flexibility in the human fungal pathogen Aspergillus fumigatus.Current biology : CB · 2026Article
- Whole-chromosome duplications drive antimicrobial resistance inbioRxiv : the preprint server for biology · 2025Article
- Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection.Nature microbiology · 2021Article
- Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus.Microbiology spectrum · 2021Article
- The sino-nasal warzone: transcriptomic and genomic studies on sino-nasal aspergillosis in dogs.NPJ biofilms and microbiomes · 2020Article
- Genomic and phenotypic analysis of COVID-19-associated pulmonary aspergillosis isolates ofbioRxiv : the preprint server for biology · 2020Article
- Influence of genetic diversity of seventeen Beauveria bassiana isolates from different hosts on virulence by comparative genomics.BMC genomics · 2020Article
- Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae.PLoS neglected tropical diseases · 2020Article
- Comparative genomics and association analysis identifies virulence genes of Cercospora sojina in soybean.BMC genomics · 2020Article
- The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus.Nature communications · 2020Article
- Cryptic species ofVirulence · 2019Article
- Identification of a Polyketide Synthase Gene Responsible for Ascochitine Biosynthesis inmSphere · 2019Article
- Proteomic Analysis of the Responses ofJournal of fungi (Basel, Switzerland) · 2019Article
- Revealing the Virulence Potential of Clinical and EnvironmentalFrontiers in microbiology · 2019Article
- The Use ofJournal of fungi (Basel, Switzerland) · 2018Review
- Characterisation of the cellular and proteomic response of Galleria mellonella larvae to the development of invasive aspergillosis.BMC microbiology · 2018Article
- Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species.PLoS biology · 2017Article
- Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.Genome biology · 2017Article
- Rodent Models of Invasive Aspergillosis due toFrontiers in microbiology · 2017Review
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
Abstract
Nonribosomal peptide synthesis (NRPS) is a documented virulence factor for the opportunistic pathogen Aspergillus fumigatus and other fungi. Secreted or intracellularly located NRP products include the toxic molecule gliotoxin and the iron-chelating siderophores triacetylfusarinine C and ferricrocin. No structural or immunologically relevant NRP products have been identified in the organism. We investigated the function of the largest gene in A. fumigatus, which encodes the NRP synthetase Pes3 (AFUA_5G12730), by targeted gene deletion and extensive phenotypic analysis. It was observed that in contrast to other NRP synthetases, deletion of pes3 significantly increases the virulence of A. fumigatus, whereby the pes3 deletion strain (A. fumigatus Δpes3) exhibited heightened virulence (increased killing) in invertebrate (P < 0.001) and increased fungal burden (P = 0.008) in a corticosteroid model of murine pulmonary aspergillosis. Complementation restored the wild-type phenotype in the invertebrate model. Deletion of pes3 also resulted in increased susceptibility to the antifungal, voriconazole (P < 0.01), shorter germlings, and significantly reduced surface β-glucan (P = 0.0325). Extensive metabolite profiling revealed that Pes3 does not produce a secreted or intracellularly stored NRP in A. fumigatus. Macrophage infections and histological analysis of infected murine tissue indicate that Δpes3 heightened virulence appears to be mediated by aberrant innate immune recognition of the fungus. Proteome alterations in A. fumigatus Δpes3 strongly suggest impaired germination capacity. Uniquely, our data strongly indicate a structural role for the Pes3-encoded NRP, a finding that appears to be novel for an NRP synthetase.
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