title: Apolipoprotein A-I exerts bactericidal activity against Yersinia enterocolitica serotype O:3.
abstract: Apolipoprotein A-I (apoA-I), the main protein component of high density lipoprotein (HDL), is well recognized for its antiatherogenic, antioxidant, and antiinflammatory properties. Here, we report a novel role for apoA-I as a host defense molecule that contributes to the complement-mediated killing of an important gastrointestinal pathogen, Gram-negative bacterium Yersinia enterocolitica. We specifically show that the C-terminal domain of apoA-I is the effector site providing the bactericidal activity. Although the presence of the lipopolysaccharide O-antigen on the bacterial surface is absolutely required for apoA-I to kill the bacteria, apoA-I does not interact with the bacteria directly. To the contrary, exposure of the bacteria by serum proteins triggers apoA-I deposition on the bacterial surface. As our data show that both purified lipid-free and HDL-associated apoA-I displays anti-bacterial potential, apoA-I mimetic peptides may be a promising therapeutic agent for the treatment of certain Gram-negative infections.
authors: Department of Chronic Disease Prevention, Public Health Genomics Research Unit, National Institute for Health and Welfare, and Institute for Molecular Medicine Finland (FIMM), 00290 Helsinki, Finland. Electronic address: marta.biedzka-sarek@thl.fi.
authors: Marta
authors: M
authors: Biedzka-Sarek
authors: Department of Chronic Disease Prevention, Public Health Genomics Research Unit, National Institute for Health and Welfare, and Institute for Molecular Medicine Finland (FIMM), 00290 Helsinki, Finland.
authors: Jari
authors: J
authors: Metso
authors: Department of Molecular Genetics, Boston University Medical Center, Boston, Massachusetts 02118.
authors: Andreas
authors: A
authors: Kateifides
authors: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland; Department of Laboratory Diagnostics, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors: Taru
authors: T
authors: Meri
authors: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.
authors: T Sakari
authors: TS
authors: Jokiranta
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602.
authors: Artur
authors: A
authors: Muszyński
authors: Institute of Microbiology, University of Silesia, 40 032 Katowice, Poland.
authors: Joanna
authors: J
authors: Radziejewska-Lebrecht
authors: Department of Molecular Genetics, Boston University Medical Center, Boston, Massachusetts 02118.
authors: Vassilis
authors: V
authors: Zannis
authors: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland; Department of Laboratory Diagnostics, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors: Mikael
authors: M
authors: Skurnik
authors: Department of Chronic Disease Prevention, Public Health Genomics Research Unit, National Institute for Health and Welfare, and Institute for Molecular Medicine Finland (FIMM), 00290 Helsinki, Finland.
authors: Matti
authors: M
authors: Jauhiainen
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001665:Binding Sites; D003165:Complement System Proteins; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D009154:Mutation; D019081:O Antigens / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature; D015008:Yersinia enterocolitica / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D016632:Apolipoprotein A-I; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D019081:O Antigens; D010455:Peptides; D003165:Complement System Proteins