Disease relevance of Spirochaetales

• Fibronectin tetrapeptide is target for syphilis spirochete cytadherence [1].
• Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) in human peripheral blood mononuclear cells [2].
• The Lyme disease spirochete Borrelia burgdorferi has bundles of periplasmic flagella subpolarly located at each cell end [3].
• Bell's palsy and secondary syphilis: CSF spirochetes detected by immunofluorescence [4].
• An endopeptidase was purified to homogeneity from the cell extracts of Treponema denticola ATCC 35405 (a human oral spirochete) by a procedure that comprised dialysis, anion exchange fast protein liquid chromatography (FPLC), hydroxylapatite FPLC, immobilized metal affinity FPLC, FPLC chromatofocusing, and two consecutive gel permeation FPLC steps [5].

Psychiatry related information on Spirochaetales

• It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition [6].

High impact information on Spirochaetales

• PLG was not detected in spirochetes from unfed ticks, but binding occurred as ticks fed on the host's blood [7].
• Acetogenesis from H2 plus CO2 by spirochetes from termite guts [8].
• Mice given both P35 and P37 antisera were protected from challenge with 10(2) B. burgdorferi, and P35 and P37 antisera also afforded protection when administered 24 hr after spirochete challenge [9].
• They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins [10].
• In immunocompetent mice, spirochetes that did not express ospC (the outer-surface protein C gene) were selected within 17 d after inoculation, concomitantly with the emergence of anti-OspC antibody [11].

Chemical compound and disease context of Spirochaetales

• Moreover, results from three independent methodologies, i.e., (a) indirect immunofluorescence analysis of agarose-encapsulated organisms, (b) proteinase K treatment of intact spirochetes, and (c) Triton X-114 phase partitioning of T. pallidum conclusively demonstrated that native TprK is entirely periplasmic [12].
• Accordingly, we determined whether antigenically variable spirochetes delivered by naturally infected ticks, collected from a site where transmission is intense, may fail to infect mice actively immunized with recombinant glutathione transferase outer surface fusion proteins A or B (OspA and OspB) [13].
• Subcutaneous inoculation of 10(4) spirochetes resulted in a peak spirochetemia five days after infection with 20-23 x 10(6) organisms per milliliter of whole blood in all mice, indicating that the PAS had no effect on the development of this phase of the infection [14].
• The spirochetes were eliminated upon treatment with neomycin and bacitracin, but the symptoms of the patients remained unchanged [15].
• This contrasted with the intense fluorescence observed when encapsulated spirochetes were probed in the presence of 0.06% Triton X-100, which selectively removed outer membranes [16].

Biological context of Spirochaetales

• This is, to our knowledge, the first description of the targeted disruption of a candidate B. burgdorferi virulence factor with a known biochemical function that can be quantified, and demonstrates the importance of B. burgdorferi P66 in the attachment of this pathogenic spirochete to a human cell-surface receptor [17].
• The results indicate that asymmetrical rotation of the flagellar bundles of spirochetes does not depend upon the chemotaxis system but rather upon differences between the two flagellar bundles [3].
• Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to avoid the immune response [18].
• Coiling phagocytosis discriminates between different spirochetes and is enhanced by phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor [19].
• Consistent with this, the spirochete bound to immobilized heparin, and soluble heparin inhibited bacterial adhesion to mammalian cells [20].

Anatomical context of Spirochaetales

• While macrophages from TLR2(-/-) mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes [21].
• These observations suggest that synovial V delta 1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes [22].
• The ability to agglutinate erythrocytes was associated with the ability of the spirochete to bind to the sulfated polysaccharide dextran sulfate and to mammalian cells [20].
• Outer membrane destabilization by Fab-CB2, but not cell wall or cytoplasmic membrane alterations, was demonstrated experimentally by the sequential treatment of spirochetes with Fab-CB2 and monoclonal antibodies to flagellin and DnaK [23].
• Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro [24].

Gene context of Spirochaetales

• IL-1 beta synthesis increased in response to increasing numbers of spirochetes, whereas IL-1ra synthesis did not [2].
• These studies indicate opposing roles for IL-4 and IFN-gamma in the modulation of spirochete growth and disease development in B. burgdorferi-infected mice and suggest that differential cytokine production early in infection may contribute to strain-related differences in susceptibility [25].
• Overall, these data indicated that the p38 MAP kinase pathway plays an important role in B. burgdorferi-elicited inflammation and point to potential new therapeutic approaches to the treatment of inflammation induced by the spirochete [26].
• The results are consistent with a major role played by IL-10 in controlling the initial phase of infection with this spirochete [27].
• No TNF-alpha or IL-1beta were produced by LN cells from infected mice of either strain in response to lipoprotein or B. burgdorferi spirochetes [28].

Analytical, diagnostic and therapeutic context of Spirochaetales

• By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse [29].
• The expression of VspB by spirochetes in the blood was demonstrated in Coomassie blue-stained polyacrylamide gels and Western blots with a specific monoclonal antibody [30].
• When 10 spirochetes per endothelial cell were added, IL-8 was detected after 4 h of coculture [31].
• The titration of spirochetes revealed a dose-independent cytokine response, where 10(3) to 10(7) B. burgdorferi organisms induced similar TNF-like activities but only 10(7) spirochetes induced measurable IL-1-like activities [32].
• Similar results were achieved for actively immune mice challenged by transplantation and by passive immunization with sera from mice infected with each of the Borrelia species and then challenged with cultured spirochetes [33].

References