tailieunhanh - Báo cáo khoa học: A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus

Aspergillus fumigatusis an important human fungal pathogen. The Asper-gillus 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 fumigatuswas observed. | iFEBS Journal A nonribosomal peptide synthetase Pes1 confers protection against oxidative stress in Aspergillus fumigatus Emer P. Reeves1 Kathrin Reiber1 Claire Neville1 Olaf Scheibner2 Kevin Kavanagh1 and Sean Doyle1 1 National institute for Cellular Biotechnology Department of Biology National university of Ireland Maynooth Co. Kildare Ireland 2 Leibniz-Institute for NaturalProduct Research and Infection Biology Hans-Knoll-Institute Jena Germany Keywords chronic granulomatous disease Galleria mellonella nonrobosomalpeptide synthetase proteomics Correspondence S. Doyle NationalInstitute for Cellular Biotechnology Department of Biology National university of Ireland Maynooth Co. Kildare Ireland Fax 353 1 7083845 Tel 353 1 7083858 E-mail Website http Received 3 March 2006 revised 8 May 2006 accepted 10 May 2006 doi 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 pesl in four strains of Aspergillus fumigatus was observed. The pattern of pesl 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 pesl disruption mutant Dpesl of Aspergillus fumigatus strain was generated and confirmed by Southern and western analysis in addition to RT-PCR. The Dpesl mutant also showed significantly reduced virulence in the Galleria mellonella model system P and increased sensitivity to oxidative stress P in culture and during neutrophil-mediated phagocytosis.