title: Above and beyond C5a Receptor Targeting by Staphylococcal Leucotoxins: Retrograde Transport of Panton-Valentine Leucocidin and γ-Hemolysin.
abstract: Various membrane receptors associated with the innate immune response have recently been identified as mediators of the cellular action ofStaphylococcus aureusleucotoxins. Two of these, the Panton-Valentine leucotoxin LukS-PV/LukF-PV and the γ-hemolysin HlgC/HlgB, bind the C5a complement-derived peptide receptor. These leucotoxins utilize the receptor to induce intracellular Ca2+release from internal stores, other than those activated by C5a. The two leucotoxins are internalized with the phosphorylated receptor, but it is unknown whether they divert retrograde transport of the receptor or follow another pathway. Immunolabeling and confocal microscopic techniques were used to analyze the presence of leucotoxins in endosomes, lysosomes, endoplasmic reticulum, and Golgi. The two leucotoxins apparently followed retrograde transport similar to that of the C5a peptide-activated receptor. However, HlgC/HlgB reached the Golgi network very early, whereas LukS-PV/LukF-PV followed slower kinetics. The HlgC/HlgB leucotoxin remained in neutrophils 6 h after a 10-min incubation of the cells in the presence of the toxin with no signs of apoptosis, whereas apoptosis was observed 3 h after neutrophils were incubated with LukS-PV/LukF-PV. Such retrograde transport of leucotoxins provides a novel understanding of the cellular effects initiated by sublytic concentrations of these toxins.
authors.affiliation: Fédération de Médecine Translationnelle de Strasbourg (FMTS), VBP EA7290, Institut de Bactériologie, Université de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France. zimmermann.gaelle@gmail.com.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Zimmermann-Meisse
authors.affiliation: Fédération de Médecine Translationnelle de Strasbourg (FMTS), VBP EA7290, Institut de Bactériologie, Université de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France. prevost@unistra.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Prévost
authors.affiliation: Fédération de Médecine Translationnelle de Strasbourg (FMTS), VBP EA7290, Institut de Bactériologie, Université de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France. jover@unistra.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jover
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D001692:Biological Transport; D020013:Calcium Signaling; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology; D011992:Endosomes / Q000378:metabolism / Q000382:microbiology; D005098:Exotoxins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism / Q000382:microbiology; D006460:Hemolysin Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007700:Kinetics; D007956:Leukocidins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C488033:C5AR1 protein, human; D005098:Exotoxins; D006460:Hemolysin Proteins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D044087:Receptor, Anaphylatoxin C5a; C037956:gamma-hemolysin, Staphylococcus aureus; C018579:leukotoxin
keywords: C5aR binding leucotoxins; Fura-2 Calcium fluorimetry; Staphylococcus aureus; confocal microscopy; human neutrophils; retrograde transport