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A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus
Author(s) -
Reeves Emer P.,
Reiber Kathrin,
Neville Claire,
Scheibner Olaf,
Kavanagh Kevin,
Doyle Sean
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05315.x
Subject(s) - aspergillus fumigatus , biology , nonribosomal peptide , virulence , microbiology and biotechnology , oxidative stress , mutant , gene , biochemistry , biosynthesis
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 (Δ pes1 ) of Aspergillus fumigatus strain 293.1 was generated and confirmed by Southern and western analysis, in addition to RT‐PCR. The Δ 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.