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Lab of Industrial Microbiology, Korea university 2010010566 Hyeon Jeong Eun Introduction • Adhesion & Flocculation - One of the most critical functions of the cell surface - Prevents cells from being washed away - Allows them to form biofilms that offer protection ability Fungal (Yeast) Adhesion 1) Adhere to abiotic surfaces such as plastic 2) Cell-Cell adhesion ( Flocculation ) =>Phenotypic variability and plasticity Introduction • Biofilm - A complex aggregation of microorganisms marked by the excretion of a protective and adhesive matrix -J. Valle et al., “Broad-spectrum biofilm inhibition by a secreted bacterial polysaccharide,” PNAS 103(33): 1255812563. 2006. Medical and industrial relevance of fungal adhesion 1) The remarkable plasticity -> New drugs 2) Separate biomass from various fermentation products • Adhesins or Flocculins ; Specialized cell-surface proteins - Bind specific amino acid or sugar residues A common three-domain structure 1) C-terminal : Glycosylphosphatidylinositol (GPI)-anchor 2) N-terminal : Carbohydrate or peptide binding domain 3) Middle domain : Multiple serine and threonine-rich repeats • Fig1. Secretion and cell-surface anchoring of fungal adhesins • FigS1. Phylogenetic tree of cellular adhesins and mucins • Fig2. Cell-cell and cell-surface adhesion associated with the S. cerevisiae FLO genes [1] Expresses the FLO1 [2] Does not express any FLO gene [3] Overexpresses FLO11 • Different of mechanisms of adhesion 1) Lectin-like adhesion (sugar sensitive) • N-terminus : lectin-like carbohydrate binding domain • Two sub-categories - Flo1 group : only binds mannose sugars - NewFlo group : binds various sugars 2) Sugar-insensitive adhesion • bind peptides or increase the cell-surface hydrophobicity • Controlled by several signaling pathways - Triggered by certain stress factors and/or nutrient limitation FLO11-mediated cell-surface adhesion 1) Ras-cAMP pathway 2) MAP kinase-dependent filamentous growth pathway 3) The main glucose repression pathway ( not yet known ) 4) Target of Rapamycin (TOR) pathway – nitrogen starvation 5) Transcription factors Sok2, Phd1, Adh1 – Epistatic pathway • Fig3A. The MAPK-dependent filamentous growth pathway Ste11, Ste7 : Central kinase Msb2 : mucin-like transmembrane protein Mep2 : Ammonium permease • Fig3B. The Ras/cAMP/PKA pathway Cyr1 : adenylate cyclase PKA : Protein kinase A complex Sfl1 : Suppressor of flocculation • Fig3B. The main glucose repression pathway Hxt : Hexose transporters Hxk : Hexokinases Sfl1 : Suppressor of flocculation • Controlled epigenetically 1) Cells regulary switch between the states ( transcribed <-> silent ) 2) Stochastic switching mechanism ( Nonsense mutation ) 3) Chromatin remodeling Goals of adhesins silencing 1) Balance between adhering, colonizing cells and non-adhering cells 2) Proactively anticipate new conditions in fluctuating environments 3) Allowing them to adhere to specific surfaces only 4) Different subsets may allow evasion of the host immune system • Recombination of Intragenic repeats ; Novel adhesins - Fastest expanding group of paralogues in the genomes The driving force behind the creation of novel adhesins 1) Trigger frequent slippage, recombination events - Longer adhesins generally confer greater adherence 2) Recombination events between repeats of different genes - Generate chimeirc forms • Fig4. Box plot of the S. cerevisiae FLO1 nucleotide sequence Conclusion • Fungal adhesion is an unusually complex and variable phenotype 1) Quickly adapt their adhesive properties to a particular environments 2) Many different genetic and epigenetic signaling cascades 3) The internal tandem repeats trigger frequent recombination events • For Industrial applications, the instability of the flocculation profile is a true nightmare Recombinant DNA techniques • For Medical applications, the remarkable plasticity of fungal adhesion also causes concern Targets for new drugs