title: Structural Relationship of the Lipid A Acyl Groups to Activation of Murine Toll-Like Receptor 4 by Lipopolysaccharides from Pathogenic Strains of Burkholderia mallei, Acinetobacter baumannii, and Pseudomonas aeruginosa.
abstract: Toll-like receptor 4 (TLR4) is required for activation of innate immunity upon recognition of lipopolysaccharide (LPS) of Gram-negative bacteria. The ability of TLR4 to respond to a particular LPS species is important since insufficient activation may not prevent bacterial growth while excessive immune reaction may lead to immunopathology associated with sepsis. Here, we investigated the biological activity of LPS from Burkholderia mallei that causes glanders, and from the two well-known opportunistic pathogens Acinetobacter baumannii and Pseudomonas aeruginosa (causative agents of nosocomial infections). For each bacterial strain, R-form LPS preparations were purified by hydrophobic chromatography and the chemical structure of lipid A, an LPS structural component, was elucidated by HR-MALDI-TOF mass spectrometry. The biological activity of LPS samples was evaluated by their ability to induce production of proinflammatory cytokines, such as IL-6 and TNF, by bone marrow-derived macrophages. Our results demonstrate direct correlation between the biological activity of LPS from these pathogenic bacteria and the extent of their lipid A acylation.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia ; Biological Faculty, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Korneev
authors.affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Arbatsky
authors.affiliation: Department of Chemical Sciences, Università di Napoli Federico II , Naples , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.affiliation: CNR Institute for Polymers Composites and Biomaterials , Catania , Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Palmigiano
authors.affiliation: State Research Centre of Applied Microbiology and Biotechnology , Obolensk , Russia.
authors.forename: Rima Z
authors.initials: RZ
authors.lastname: Shaikhutdinova
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Shneider
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
authors.affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Kondakova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia ; Biological Faculty, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: Ekaterina N
authors.initials: EN
authors.lastname: Sviriaeva
authors.affiliation: CNR Institute for Polymers Composites and Biomaterials , Catania , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.affiliation: CNR Institute for Polymers Composites and Biomaterials , Catania , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Garozzo
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia ; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Kruglov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia ; Biological Faculty, Lomonosov Moscow State University , Moscow , Russia ; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Drutskaya
authors.affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Moscow , Russia.
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Knirel
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia ; Biological Faculty, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kuprash
keywords: Gram-negative bacteria; acyl chains; innate immunity; lipid A; macrophages; proinflammatory cytokines