A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus
Abstract
Aspergillus fumigatus is an important human fungal pathogen. The Aspergillus fumigatus genome contains 14 nonribosomal peptide synthetase genes, potentially responsible for generating metabolites that contribute to organismal virulence. Differential expression of the nonribosomal peptide synthetase gene, pes1, in four strains of Aspergillus fumigatus was observed. The pattern of pes1 expression differed from that of a putative siderophore synthetase gene, sidD, and so is unlikely to be involved in iron acquisition. The Pes1 protein (expected molecular mass 698 kDa) was partially purified and identified by immunoreactivity, peptide mass fingerprinting (36% sequence coverage) and MALDI LIFT-TOF/TOF MS (four internal peptides sequenced). A pes1 disruption mutant (delta pes1) of Aspergillus fumigatus strain 293.1 was generated and confirmed by Southern and western analysis, in addition to RT-PCR. The delta pes1 mutant also showed significantly reduced virulence in the Galleria mellonella model system (P < 0.001) and increased sensitivity to oxidative stress (P = 0.002) in culture and during neutrophil-mediated phagocytosis. In addition, the mutant exhibited altered conidial surface morphology and hydrophilicity, compared to Aspergillus fumigatus 293.1. It is concluded that pes1 contributes to improved fungal tolerance against oxidative stress, mediated by the conidial phenotype, during the infection process.
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Besides srbA itself, the gene with the highest fold difference in expression in SDW1 is a non-ribosomal peptide synthetase, AFUA_1g10380 (NRPS1 or pes1).
“Interestingly, besides srbA itself, the gene with the highest fold difference in expression in SDW1 is a non-ribosomal peptide synthetase, AFUA_1g10380 (NRPS1 or pes1) [43],[44].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [44]
NRPS1 (or pes1) had the highest change in expression between wild type and the SrbA null mutant.
“For example, a non-ribosomal peptide synthetase, NRPS1 (or pes1), had the highest change in expression between wild type and the SrbA null mutant [43],[44].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [44]
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- Authors
- Reeves, E. P., Reiber, K., Neville, C., Scheibner, O., Kavanagh, K., & Doyle, S.
- Affiliations
- National University of Ireland, Maynooth (IE)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2006-06-06
- Volume
- 273
- Issue
- 13
- Pages
- 3038-3053
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W1992074789
- Cited by
- 70
- References
- 58
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Maynooth University ePrints and eTheses Archive (Maynooth University) (acceptedVersion)
- Funders
- Wellcome Trust
- National Institute of Allergy and Infectious Diseases (U01 AI48830, U01AI048830)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Aspergillus fumigatus, nonribosomal peptide synthetase, PES1, oxidative stress resistance, fungal virulence, Galleria mellonella, iron acquisition, fungal pathogens
- MeSH terms
- Aspergillus fumigatus, Base Sequence, Cloning, Molecular, Fungal Proteins, Genes, Fungal, Molecular Sequence Data, Peptide Synthases, Phenotype, Time Factors, Genome, Fungal, Oxidative Stress, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction
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