title: Activation of neutrophils by the two-component leukotoxin LukE/D from Staphylococcus aureus: proteomic analysis of the secretions.
abstract: Staphylococcus aureus is responsible for severe bacterial infections in hospitals and healthcare facilities. It produces single and bicomponent toxins (leukotoxins and hemolysins) that hinder innate immune function. Leukotoxin subunits bind to leukocyte cell membrane thus inducing transmembrane pores and subsequently, cell lysis. Leukotoxin LukE/D is a member of the bicomponent toxin family, but to date, no study concerning its involvement in host-pathogen interactions has been reported. In the present study, we performed the proteomic analysis of the secretions recovered after activation of human neutrophils by leukotoxin LukE/D. The neutrophil secretions were purified by RP-HPLC and different fractions were analyzed by Edman sequencing, LC-MS/MS, immunoblotted for chromogranin-derived peptides and further analyzed for antimicrobial properties. Proteomic analysis revealed that neutrophil secretions constitute a large number of proteins related with immune boosting mechanisms, proteolytic degradation, inflammatory process and antioxidant reactions.
authors.affiliation: Inserm UMR 1121, Université de Strasbourg, Strasbourg F-67000, France.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Aslam
authors.forename: Benoît-Joseph
authors.initials: BJ
authors.lastname: Laventie
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.forename: Gilles
authors.initials: G
authors.lastname: Prévost
authors.forename: Daniel
authors.initials: D
authors.lastname: Keller
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Strub
authors.forename: Alain van
authors.initials: Av
authors.lastname: Dorsselaer
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haikel
authors.forename: Corinne
authors.initials: C
authors.lastname: Taddei
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
mesh_terms: D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D002853:Chromatography, Liquid; D002864:Chromogranins / Q000737:chemistry; D005098:Exotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016982:Micrococcus luteus / Q000187:drug effects / Q000254:growth & development; D058977:Molecular Sequence Annotation; D009492:Neurospora crassa / Q000187:drug effects / Q000254:growth & development; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis*; D020543:Proteome / Q000032:analysis*; D013211:Staphylococcus aureus / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D023084:alpha-Defensins / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D002864:Chromogranins; D005098:Exotoxins; D010446:Peptide Fragments; D020543:Proteome; D023084:alpha-Defensins; C018579:leukotoxin