Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus fumigatus

被引:51
作者
Lin, Chi-Jan [1 ]
Sasse, Christoph [1 ]
Gerke, Jennifer [1 ]
Valerius, Oliver [1 ]
Irmer, Henriette [1 ]
Frauendorf, Holm [2 ]
Heinekamp, Thorsten [3 ,4 ]
Strassburger, Maria [3 ,4 ]
Van Tuan Tran [1 ]
Herzog, Britta [1 ]
Braus-Stromeyer, Susanna A. [1 ]
Braus, Gerhard H. [1 ]
机构
[1] Univ Gottingen, Inst Microbiol & Genet, Dept Mol Microbiol & Genet, D-37073 Gottingen, Germany
[2] Univ Gottingen, Inst Organ & Biomol Chem, D-37073 Gottingen, Germany
[3] Leibniz Inst Nat Prod Res & Infect Biol HKI, Mol & Appl Microbiol, Jena, Germany
[4] Univ Jena, Inst Microbiol, Jena, Germany
关键词
PROTEIN-KINASE-A; SACCHAROMYCES-CEREVISIAE; ASEXUAL DEVELOPMENT; GENE-EXPRESSION; SIGNALING PATHWAYS; HYPHAL DEVELOPMENT; CATALYTIC SUBUNIT; FUNGAL PATHOGENS; CELL-ADHESION; IDENTIFICATION;
D O I
10.1371/journal.ppat.1005205
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The transcription factor Flo8/Som1 controls filamentous growth in Saccharomyces cerevisiae and virulence in the plant pathogen Magnaporthe oryzae. Flo8/Som1 includes a characteristic N-terminal LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain and is activated by the cAMP dependent protein kinase A signaling pathway. Heterologous SomA from Aspergillus fumigatus rescued in yeast flo8 mutant strains several phenotypes including adhesion or flocculation in haploids and pseudohyphal growth in diploids, respectively. A. fumigatus SomA acts similarly to yeast Flo8 on the promoter of FLO11 fused with reporter gene (LacZ) in S. cerevisiae. FLO11 expression in yeast requires an activator complex including Flo8 and Mfg1. Furthermore, SomA physically interacts with PtaB, which is related to yeast Mfg1. Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development. Only aerial hyphae without further differentiation could be formed. The deletion phenotype was verified by a conditional expression of somA using the inducible Tet-on system. A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation. A ptaB deletion strain showed a similar phenotype supporting that the SomA/PtaB complex controls A. fumigatus biofilm formation. Transcriptional analysis showed that SomA regulates expression of genes for several transcription factors which control conidiation or adhesion of A. fumigatus. Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity. These data corroborate a complex control function of SomA acting as a central factor of the transcriptional network, which connects adhesion, spore formation and virulence in the opportunistic human pathogen A. fumigatus.
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页数:34
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共 93 条
[11]  
Braus GH, 2003, MOL BIOL CELL, V14, P4272, DOI 10.1091/mbc.E03-01-0042
[12]   Choosing the right lifestyle: adhesion and development in Saccharomyces cerevisiae [J].
Brueckner, Stefan ;
Moesch, Hans-Ulrich .
FEMS MICROBIOLOGY REVIEWS, 2012, 36 (01) :25-58
[13]   The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans [J].
Cao, F ;
Lane, S ;
Raniga, PP ;
Lu, Y ;
Zhou, Z ;
Ramon, K ;
Chen, JY ;
Liu, HP .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (01) :295-307
[14]   FungalRV: adhesin prediction and immunoinformatics portal for human fungal pathogens [J].
Chaudhuri, Rupanjali ;
Ansari, Faraz Alam ;
Raghunandanan, Muthukurussi Varieth ;
Ramachandran, Srinivasan .
BMC GENOMICS, 2011, 12
[15]   MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification [J].
Cox, Juergen ;
Mann, Matthias .
NATURE BIOTECHNOLOGY, 2008, 26 (12) :1367-1372
[16]   Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick [J].
de Groot, Piet W. J. ;
Bader, Oliver ;
de Boer, Albert D. ;
Weig, Michael ;
Chauhan, Neeraj .
EUKARYOTIC CELL, 2013, 12 (04) :470-481
[17]   Identification of a cAMP-dependent protein kinase catalytic subunit required for virulence and morphogenesis in Ustilago maydis [J].
Dürrenberger, F ;
Wong, K ;
Kronstad, JW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5684-5689
[18]   StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans [J].
Dutton, JR ;
Johns, S ;
Miller, BL .
EMBO JOURNAL, 1997, 16 (18) :5710-5721
[19]   Differential Flo8p-dependent regulation of FLO1 and FLO11 for cell-cell and cell-substrate adherence of S-cerevisiae S288c [J].
Fichtner, Lars ;
Schulze, Florian ;
Braus, Gerhard H. .
MOLECULAR MICROBIOLOGY, 2007, 66 (05) :1276-1289
[20]   Galactosaminogalactan, a New Immunosuppressive Polysaccharide of Aspergillus fumigatus [J].
Fontaine, Thierry ;
Delangle, Aurelie ;
Simenel, Catherine ;
Coddeville, Bernadette ;
van Vliet, Sandra J. ;
van Kooyk, Yvette ;
Bozza, Silvia ;
Moretti, Silvia ;
Schwarz, Flavio ;
Trichot, Coline ;
Aebi, Markus ;
Delepierre, Muriel ;
Elbim, Carole ;
Romani, Luigina ;
Latge, Jean-Paul .
PLOS PATHOGENS, 2011, 7 (11)