title: A macrophage-stimulating compound from a screen of microbial natural products.
abstract: Rising rates of antibiotic resistance in bacterial pathogens is a medical crisis of global concern that necessitates the development of new treatment strategies. We have isolated a natural product with macrophage-stimulating activity from a screen of microbially produced bioactive molecules. Streptazolin increased bacterial killing and elaboration of immunostimulatory cytokines by macrophages in vitro. Furthermore, we show that streptazolin stimulates the macrophage nuclear factor κB (NF-κB) pathway via phosphatidylinositide 3-kinase (PI3K) signaling, and that the conjugated diene moiety is essential for stimulatory activity. Immunostimulatory molecules like streptazolin represent entries into new treatment paradigms to address the challenge of antibiotic resistance.
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, Hamilton, Ontario, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Perry
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, Hamilton, Ontario, Canada.
authors.forename: Kalinka
authors.initials: K
authors.lastname: Koteva
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Verschoor
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, Hamilton, Ontario, Canada.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Dawn M E
authors.initials: DM
authors.lastname: Bowdish
authors.affiliation: 1] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada [2] Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, Hamilton, Ontario, Canada [3] Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gerry D
authors.initials: GD
authors.lastname: Wright
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods; D024881:Drug Resistance, Bacterial; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D016207:Cytokines; D016328:NF-kappa B; D010880:Piperidines; C428165:streptazolin; D058539:Phosphatidylinositol 3-Kinase