title: N-terminal ArgD peptides from the classical Staphylococcus aureus Agr system have cytotoxic and proinflammatory activities.
abstract: AgrD is the precursor for the autoinducing peptide in a quorum-sensing system regulating virulence phenotypes of the preeminent pathogen Staphylococcus aureus. Mass spectrometry-based methods, including molecular networking, identified formylated and nonformylated peptide variants derived from the AgrD N-terminal leader domain in S. aureus cell-free culture supernatants. Functional assessment of these peptides revealed unexpected bioactivities, including human cell-line cytotoxicity, modulation of neutrophil chemotaxis, neutrophil extracellular trap formation, and the aggravation of skin lesions in vivo.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gonzalez
authors.forename: Ross
authors.initials: R
authors.lastname: Corriden
authors.forename: Kathryn
authors.initials: K
authors.lastname: Akong-Moore
authors.forename: Joshua
authors.initials: J
authors.lastname: Olson
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D018450:Disease Progression; D065206:Extracellular Traps / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013203:Staphylococcal Infections / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: C414532:AgrD protein, Staphylococcus; D001426:Bacterial Proteins; D010446:Peptide Fragments; D010455:Peptides; D010456:Peptides, Cyclic