Cited by 70Microbial Natural Products and BiosynthesisFungal and yeast genetics researchAntifungal resistance and susceptibility

A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus

Reeves, Emer P., Reiber, Kathrin, Neville, Claire, Scheibner, Olaf, Kavanagh, Kevin, Doyle, Sean·2006·The FEBS Journal

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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Crossref · 10.1111/j.1742-4658.2006.05315.x

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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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