title: Anti-microbial properties of histone H2A from skin secretions of rainbow trout, Oncorhynchus mykiss.
abstract: Skin exudates of rainbow trout contain a potent 13.6 kDa anti-microbial protein which, from partial internal amino acid sequencing, peptide mass fingerprinting, matrix-associated laser desorption/ionization MS and amino acid analysis, seems to be histone H2A, acetylated at the N-terminus. The protein, purified to homogeneity by ion-exchange and reversed-phase chromatography, exhibits powerful anti-bacterial activity against Gram-positive bacteria, with minimal inhibitory concentrations in the submicromolar range. Kinetic analysis revealed that at a concentration of 0.3 microM all test bacteria lose viability after 30 min incubation. Weaker activity is also displayed against the yeast Saccharomyces cerevisiae. The protein is salt-sensitive and has no haemolytic activity towards trout erythrocytes at concentrations below 0.3 microM. Reconstitution of the protein in a planar lipid bilayer strongly disturbs the membrane but does not form stable ion channels, indicating that its anti-bacterial activity is probably not due to pore-forming properties. This is the first report to show that, in addition to its classical function in the cell, histone H2A has extremely strong anti-microbial properties and could therefore help contribute to protection against bacterial invasion.
authors.affiliation: Gatty Marine Laboratory, School of Biology, University of St Andrews, Fife KY16 8LB, Scotland, U.K.
authors.forename: Jorge M O
authors.initials: JM
authors.lastname: Fernandes
authors.forename: Graham D
authors.initials: GD
authors.lastname: Kemp
authors.forename: M Gerard
authors.initials: MG
authors.lastname: Molle
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006657:Histones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D006657:Histones; D008051:Lipid Bilayers; D012965:Sodium Chloride