title: A Salmonella SipB-derived polypeptide blocks the 'trigger' mechanism of bacterial entry into eukaryotic cells.
abstract: Entry into non-phagocytic mammalian cells by the invasive pathogens Salmonella and Shigella is triggered by the delivery of bacterial virulence effector proteins into the host cell. This is dependent upon Salmonella SipB or its Shigella homologue IpaB, which insert into the eukaryotic cell plasma membrane. Here we show that a SipB-derived 166 residue alpha-helical polypeptide is a potent inhibitor of SipB-directed liposome fusion in vitro, preventing the membrane-associated form of SipB from inserting deeply into the bilayer. This polypeptide blocks Salmonella entry into cultured mammalian cells at 10(-10) M, and is a heterologous inhibitor of analogous IpaB activity and Shigella cell entry. These findings reveal a potential strategy to identify inhibitors of the 'trigger' mechanism underlying cell entry by these major invasive pathogens.
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005057:Eukaryotic Cells / Q000382:microbiology*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012475:Salmonella / Q000472:pathogenicity*; D012760:Shigella / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D008081:Liposomes; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; C094579:invasion protein B, Salmonella typhimurium; C087447:ipaB protein, Shigella