title: Distinct biological activity of lipopolysaccharides with different lipid A acylation status from mutant strains of Yersinia pestis and some members of genus Psychrobacter.
abstract: Correlation between the chemical structure of lipid A from various Gram-negative bacteria and biological activity of their lipopolysaccharide (LPS) as an agonist of the innate immune receptor Toll-like receptor 4 was investigated. Purified LPS species were quantitatively evaluated by their ability to activate the production of tumor necrosis factor (TNF) by murine bone marrow-derived macrophages in vitro. Wild-type LPS from plague-causing bacteria Yersinia pestis was compared to LPS from mutant strains with defects in acyltransferase genes (lpxM, lpxP) responsible for the attachment of secondary fatty acid residues (12:0 and 16:1) to lipid A. Lipid A of Y. pestis double ΔlpxM/ΔlpxP mutant was found to have the chemical structure that was predicted based on the known functions of the respective acyltransferases. The structures of lipid A from two members of the ancient psychrotrophic bacteria of the genus Psychrobacter were established for the first time, and biological activity of LPS from these bacteria containing lipid A fatty acids with shorter acyl chains (C10-C12) than those in lipid A from LPS of Y. pestis or E. coli (C12-C16) was determined. The data revealed a correlation between the ability of LPS to activate TNF production by bone marrow-derived macrophages with the number and the length of acyl chains within lipid A.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. marinadru@gmail.com.
authors.forename: K V
authors.initials: KV
authors.lastname: Korneev
authors.forename: A N
authors.initials: AN
authors.lastname: Kondakova
authors.forename: N P
authors.initials: NP
authors.lastname: Arbatsky
authors.forename: K A
authors.initials: KA
authors.lastname: Novototskaya-Vlasova
authors.forename: E M
authors.initials: EM
authors.lastname: Rivkina
authors.forename: A P
authors.initials: AP
authors.lastname: Anisimov
authors.forename: A A
authors.initials: AA
authors.lastname: Kruglov
authors.forename: D V
authors.initials: DV
authors.lastname: Kuprash
authors.forename: S A
authors.initials: SA
authors.lastname: Nedospasov
authors.forename: Yu A
authors.initials: YA
authors.lastname: Knirel
authors.forename: M S
authors.initials: MS
authors.lastname: Drutskaya
mesh_terms: D000215:Acylation; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D008050:Lipid A / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D044096:Psychrobacter / Q000737:chemistry*; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015010:Yersinia pestis / Q000737:chemistry* / Q000235:genetics*
chemical_list: D008050:Lipid A; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha