title: The human antimicrobial protein psoriasin acts by permeabilization of bacterial membranes.
abstract: Psoriasin, a member of the S100 family of calcium-binding proteins (S100A7) is highly upregulated in the skin of psoriasis patients. As it has recently been found to exhibit antimicrobial activity, an important role of psoriasin in surface defence has been suggested. The similarity of the three-dimensional structures of psoriasin and amoebapore A, an ancient antimicrobial, pore-forming peptide from Entamoeba histolytica, intrigued us to investigate whether the human psoriasin is also able to permeabilize bacterial membranes. Here, we demonstrate that psoriasin exerts pore-forming activity at pH values below 6 demonstrating that disruption of microbial membranes is the basis of its antimicrobial activity at low pH. Furthermore, the killing activity of psoriasin shows pH-dependent target specificity. At neutral pH, the Gram-negative bacterium E. coli is killed apparently without compromising its membrane, whereas at low pH exclusively the Gram-positive bacterium B. megaterium is killed by permeabilization of its cytoplasmic membrane.
authors.affiliation: Institute of Biochemistry, University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Michalek
authors.forename: Christoph
authors.initials: C
authors.lastname: Gelhaus
authors.forename: Oliver
authors.initials: O
authors.lastname: Hecht
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D001410:Bacillus megaterium / Q000187:drug effects* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002473:Cell Wall / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000494:pharmacology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins
chemical_list: D002135:Calcium-Binding Proteins; D011994:Recombinant Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human