Disease relevance of FTL_0137

• This review summarizes what is known about the pathogenesis of tularemia with a focus on bacterial surface components such as lipopolysaccharide and capsule as well as information obtained from the F. tularensis subsp. tularensis SCHU S4 genome [1].
• Phase variation in Francisella tularensis affecting intracellular growth, lipopolysaccharide antigenicity and nitric oxide production [2].
• Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria [3].
• Purified F. tularensis LPS did not show an agonistic or antagonistic effect on the E. coli LPS-induced activation of the J774 cells [4].
• Furthermore, F. tularensis LPS did not compete with a radiolabeled lipooligosaccharide from Neisseria meningitidis for binding to LBP or to the closely related PMN granule protein, bactericidal/permeability-increasing protein [5].

High impact information on FTL_0137

• However, spontaneous variants of F. tularensis expressing an antigenically distinct LPS induce rat macrophages to produce increased levels of NO, thereby suppressing microbial intramacrophage growth [2].
• The lipid A region of LPS stimulates the immune system in a structure-dependent manner [3].
• We screened a bank of transposon insertion mutants of F. tularensis subsp. holarctica LVS for colony morphology alterations and selected a mutant with a transposon insertion in wbtA, the first gene of the predicted lipopolysaccharide O-antigen gene cluster [6].
• Basis for the failure of Francisella tularensis lipopolysaccharide to prime human polymorphonuclear leukocytes [5].
• Previous studies using mononuclear leukocytes have shown that the lipopolysaccharide (LPS) of F. tularensis is neither a typical proinflammatory endotoxin nor an endotoxin antagonist [5].

Chemical compound and disease context of FTL_0137

• A method for the partial restoration of the antibody binding capacity of Francisella tularensis lipopolysaccharide (LPS) following denaturation (dissociation) in boiling sodium dodecyl sulfate (SDS) is described [7].
• The O-specific polysaccharide, obtained by mild acid degradation of the lipopolysaccharide of Francisella tularensis strain 15, contained 2-acetamido-2,6-dideoxy-D-glucose (D-QuiNAc), 4,6-dideoxy-4-formamido-D-glucose (D-Qui4NFm), and 2-acetamido-2-deoxy-D-galacturonamide (D-GalNAcAN) in the ratios 1:1:2 [8].
• Characterization of the lipopolysaccharide and beta-glucan of the fish pathogen Francisella victoria [9].

Biological context of FTL_0137

• Also the LPS- or BLP-induced phosphorylation of the mitogen-activated protein kinase p38 and the transcription factor c-Jun was inhibited by F. tularensis LVS but not by the 23 kDa protein mutant [4].
• Immunization of mice with purified LVS LPS induced a weak specific anti-LPS immunoglobulin M (IgM) response and very little IgG; however, infection of mice with LVS bacteria resulted in vigorous IgM and IgG, particularly IgG2a, anti-LPS antibody responses [10].
• However, neither the free Lipid A nor core-O-chain produced by mild acid hydrolysis of LPS appeared able to elicit this host defense mechanism [11].
• It shows that treating mice with sub-immunogenic amounts of intact F. tularensis LPS rapidly induces an enhanced resistance to intradermal or aerogenic challenge with strains of the pathogen of varying virulence [11].
• The Yersinia enterocolitica O:9 LPS is able to induce serological cross-reactions indistinguishable from brucellosis due to a similar immunodominant epitope in the Brucella O-polysaccharide [12].

Anatomical context of FTL_0137

• Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon [10].
• Microbial ligands, including lipopolysaccharide (LPS) and bacterial lipoproteins, activate Toll-like receptors (TLR) of mononuclear phagocytes, thereby inducing proinflammatory cytokines and antimicrobial activity [4].
• By contrast, the 40 kDa protein and the two LPS preparations did not stimulate any detectable lymphocyte proliferation [13].
• Outer membranes of a lipopolysaccharide-protein complex (LPS-17 kDa protein) as chemical tularemia vaccines [14].
• We have shown by combining lipopolysaccharide (LPS) extracted and purified from Francisella tularensis live vaccine strain (LVS) with normal complement and back titrating with sensitised sheep red blood cells that the LPS activates complement [15].

Associations of FTL_0137 with chemical compounds

• Similar to the modification of lipid A with arabinosamine, lipopolysaccharide species from F. tularensis containing a phosphate-linked galactosamine could potentially influence its intracellular survival by conferring resistance to antimicrobial peptides [16].
• Lipopolysaccharide (LPS) is the major component of Gram-negative bacterial outer membrane [17].
• This simple modification to the immunoblot procedure proved helpful in identifying a monoclonal antibody specific to hot phenol-extracted F. tularensis LPS [7].
• F. tularensis LPS, which had lost its earlier capacity to bind to a particular monoclonal antibody in the normal blot procedure, did bind following the addition of the zwitterionic detergent to the polyacrylamide gel and transfer buffer [7].
• The polysaccharide part of the LPS was found to contain a nonrepetitive sequence of 20 monosaccharides as well as alanine, 3-aminobutyric acid, and a novel branched amino acid, thus confirming F. victoria as a unique species [9].

Analytical, diagnostic and therapeutic context of FTL_0137

• Enzyme-linked immunosorbent assay (ELISA) with bacterial sonicate antigen for IgM, IgA, and IgG antibodies to Francisella tularensis: comparison with bacterial agglutination test and ELISA with lipopolysaccharide antigen [18].
• Furthermore, repetitive extragenic palindromic sequences-polymerase chain reaction amplified a 4-kb DNA fragment from TI0902 that was characteristic of F. tularensis type A but not type B. The electrophoretic profile of the lipopolysaccharide of strain TI0902 was identical to that of the LVS by Western blotting with antiserum to LVS [19].
• Vaccination caused a significant rise (P < 0.01) in IgA, IgG, and IgM titers to all antigens tested, except for the IgG response to LPS [20].
• Immunoblotting indicated that the F. tularensis lipopolysaccharide is a major target for antibodies in both groups of sera [21].

References