title: Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection.
abstract: Competition for iron influences host-pathogen interactions. Pathogens secrete small iron-binding moieties, siderophores, to acquire host iron. In response, the host secretes siderophore-binding proteins, such as lipocalin 24p3, which limit siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest that bacteria use both mammalian and bacterial siderophores. In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro. In addition, mice lacking the mammalian siderophore resist E. coli infection. Finally, we show that the host responds to infection by suppressing siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Zhuoming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Scott
authors.initials: S
authors.lastname: Reba
authors.affiliation: Genetics Branch, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Suheel Kumar
authors.initials: SK
authors.lastname: Porwal
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Roxana
authors.initials: R
authors.lastname: Rojas
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Viswanathan
authors.affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106 lxd59@case.edu.
authors.forename: L
authors.initials: L
authors.lastname: Devireddy
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology / Q000502:physiology; D002177:Candidiasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D004758:Enterobactin / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005260:Female; D005841:Gentisates / Q000276:immunology* / Q000378:metabolism; D006884:Hydroxybutyrate Dehydrogenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D015151:Immunoblotting; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000276:immunology; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017262:Siderophores / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D005841:Gentisates; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C513258:Prdm1 protein, mouse; D011956:Receptors, Cell Surface; D017262:Siderophores; D014157:Transcription Factors; C029489:enterobactin receptor; C071332:Lcn2 protein, mouse; D004758:Enterobactin; D006884:Hydroxybutyrate Dehydrogenase; D000074462:Positive Regulatory Domain I-Binding Factor 1; C010925:2,5-dihydroxybenzoic acid