title: Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus.
abstract: The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus.
authors.affiliation: Division of Life Science, Daejeon University, Daejeon, 300-716, Republic of Korea. Electronic address: shinks@dju.kr.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Shin
authors.affiliation: Biomedical Omics Team, Korea Basic Science Institute (KBSI), Ohcang, 368-883, Republic of Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea; Department of Bio-Analytical Science, University of Science and Technology, Daejeon, 305-333, Republic of Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Departments of Bacteriology and Genetics, The University of Wisconsin-Madison, Madison, WI, 53706, USA. Electronic address: jyu1@wisc.edu.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Yu
mesh_terms: D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005912:Gliotoxin / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000597190:BrlA protein, Aspergillus fumigatus; D005656:Fungal Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D005912:Gliotoxin; C552832:GliT protein, Aspergillus fumigatus; D010088:Oxidoreductases
keywords: 2-DE; Asexual development; Aspergillus fumigatus; Gliotoxin; Transcription factors