title: Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners.
abstract: Lactobacillus iners is a common constituent of the human vaginal microbiota. This species was only recently characterized due to its fastidious growth requirements and has been hypothesized to play a role in the pathogenesis of bacterial vaginosis. Here we present the identification and molecular characterization of a protein toxin produced by L. iners. The L. iners genome encodes an open reading frame with significant primary sequence similarity to intermedilysin (ILY; 69.2% similarity) and vaginolysin (VLY; 68.4% similarity), the cholesterol-dependent cytolysins from Streptococcus intermedius and Gardnerella vaginalis, respectively. Clinical isolates of L. iners produce this protein, inerolysin (INY), during growth in vitro, as assessed by Western analysis. INY is a pore-forming toxin that is activated by reducing agents and inhibited by excess cholesterol. It is active across a pH range of 4.5 to 6.0 but is inactive at pH 7.4. At sublytic concentrations, INY activates p38 mitogen-activated protein kinase and allows entry of fluorescent phalloidin into the cytoplasm of epithelial cells. Unlike VLY and ILY, which are human specific, INY is active against cells from a broad range of species. INY represents a new target for studies directed at understanding the role of L. iners in states of health and disease at the vaginal mucosal surface.
authors.affiliation: Columbia University, New York, NY 10032, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Rampersaud
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Planet
authors.forename: Tara M
authors.initials: TM
authors.lastname: Randis
authors.forename: Ritwij
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Aguilar
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lehrer
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000528:radiation effects; D007778:Lactobacillus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D013312:Stress, Physiological; D014466:Ultraviolet Rays
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003603:Cytotoxins; D002784:Cholesterol