title: Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.
abstract: Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hollands
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093.
authors.forename: Ross
authors.initials: R
authors.lastname: Corriden
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gysler
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Samira
authors.initials: S
authors.lastname: Dahesh
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Joshua
authors.initials: J
authors.lastname: Olson
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Syed
authors.initials: S
authors.lastname: Raza Ali
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093.
authors.forename: Maya T
authors.initials: MT
authors.lastname: Kunkel
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Lin
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: Stefano
authors.initials: S
authors.lastname: Forli
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Newton
authors.affiliation: School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India.
authors.forename: Geetha B
authors.initials: GB
authors.lastname: Kumar
authors.affiliation: School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India.
authors.forename: Bipin G
authors.initials: BG
authors.lastname: Nair
authors.affiliation: School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India; Department of Biochemistry, University of California, Riverside, California 92521.
authors.forename: J Jefferson P
authors.initials: JJP
authors.lastname: Perry
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 920934; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093,. Electronic address: vnizet@ucsd.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D031021:Anacardium / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D065206:Extracellular Traps / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D016897:Respiratory Burst; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D048729:Anacardic Acids; D000900:Anti-Bacterial Agents; D008246:Lysophospholipids; C088115:anacardic acid; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Anacardic Acid; Neutrophil extracellular traps; PI3 kinase; antibiotic resistance; innate immunity; neutrophil; reactive oxygen species (ROS); sphingosine-1-phosphate (S1P)