Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.
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PMID:Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. 812 42

Based on monosaccharide analysis and 1H- and 13C-NMR spectroscopy, the following structure of the O-specific polysaccharide chain of Proteus vulgaris OX2 lipopolysaccharide (LPS), which defines the O2 specificity of Proteus, was established: [formula: see text] where L-QuiNAc is N-acetyl-L-quinovosamine (2-acetamido-2,6-dideoxy-L-glucose). Various strains of P. vulgaris OX2 used in the Weil-Felix test for serodiagnosis of rickettsiosis (spotted fevers, except for Rocky Mountain spotted fever) were shown to produce LPS with the same O-specific polysaccharide, which differs structurally and serologically from LPS of P. vulgaris OX19 used as antigen for serodiagnosis of typhus and Rocky Mountain spotted fever. O-Acetyl groups present in the polysaccharide are not important for manifesting the immunospecificity. ELISA confirmed that the epitope responsible for the cross-reactivity between sera from patients with Japanese spotted fever and P. vulgaris OX2 cells is located on the P. vulgaris LPS. At the same time, no cross-reaction was observed between rabbit anti-P. vulgaris OX2 antibodies and the spotted fever group (SFG) rickettsial cells. Therefore, human anti-SFG rickettsial antibodies and rabbit anti-P. vulgaris OX2 antibodies may bind to distinct epitopes on P. vulgaris OX2 LPS, and no epitope recognized by rabbit anti-P. vulgaris OX2 antibodies is present on the LPS or any other surface antigen of SFG rickettsiae.
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PMID:Structural and serological studies of the O-antigen of the bacterium Proteus vulgaris OX2 (serogroup O2) used in the Weil-Felix test. 911 24

Cutaneous biopsies of five eschars and two rash lesions from five patients from New York City with documented rickettsialpox were examined by immunohistochemical methods with a monoclonal antibody directed against spotted fever group rickettsial lipopolysaccharide for the presence and cellular location of Rickettsia akari Rickettsiae were identified in all of the five patients, with good concordance of results for the same biopsy tissues with previously reported results by the direct immunofluorescence method. In contrast with immunofluorescence, which did not reveal the location of the organisms, immunohistochemical examination demonstrated R. akari to be in perivascular cells, morphologically resembling macrophages. Evaluation with double staining for rickettsiae and either CD68 or Factor VIII-related antigen revealed that the predominant infected cell type was CD68-positive macrophages, and only a rare rickettsia was detected in vascular endothelium, the major target cell for other rickettsioses. These results provide a diagnostic method for rickettsialpox and other spotted fever group rickettsioses and indicate that the elucidation of the pathogenesis of rickettsialpox must take into account that its target cell differs from that of Rocky Mountain spotted fever, boutonneuse fever, louse-borne typhus fever, and murine typhus.
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PMID:Monoclonal antibody-based immunohistochemical diagnosis of rickettsialpox: the macrophage is the principal target. 1034 92

Members of the Rickettsia genus are obligate intracellular, Gram-negative coccobacilli that infect mammalian and arthropod hosts. Several rickettsial species are human pathogens and are transmitted by blood-feeding arthropods. In Gram-negative parasites, the outer membrane (OM) sits at the nexus of the host-pathogen interaction and is rich in lipopolysaccharide (LPS). The lipid A component of LPS anchors the molecule to the bacterial surface and is an endotoxic agonist of Toll-like receptor 4 (TLR4). Despite the apparent importance of lipid A in maintaining OM integrity, as well as its inflammatory potential during infection, this molecule is poorly characterized in Rickettsia pathogens. In this work, we have identified and characterized new members of the recently discovered LpxJ family of lipid A acyltransferases in both Rickettsia typhi and Rickettsia rickettsii, the etiological agents of murine typhus and Rocky Mountain spotted fever, respectively. Our results demonstrate that these enzymes catalyze the addition of a secondary acyl chain (C14/C16) to the 3'-linked primary acyl chain of the lipid A moiety in the final steps of the Raetz pathway of lipid A biosynthesis. Since lipid A architecture is fundamental to bacterial OM integrity, we believe that rickettsial LpxJ may be important in maintaining membrane dynamics to facilitate molecular interactions at the host-pathogen interface that are required for adhesion and invasion of mammalian cells. This work contributes to our understanding of rickettsial outer membrane physiology and sets a foundation for further exploration of the envelope and its role in pathogenesis.IMPORTANCE Lipopolysaccharide (LPS) triggers an inflammatory response through the TLR4-MD2 receptor complex and inflammatory caspases, a process mediated by the lipid A moiety of LPS. Species of Rickettsia directly engage both extracellular and intracellular immunosurveillance, yet little is known about rickettsial lipid A. Here, we demonstrate that the alternative lipid A acyltransferase, LpxJ, from Rickettsia typhi and R. rickettsii catalyzes the addition of C16 fatty acid chains into the lipid A 3'-linked primary acyl chain, accounting for major structural differences relative to the highly inflammatory lipid A of Escherichia coli.
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PMID:Rickettsia Lipid A Biosynthesis Utilizes the Late Acyltransferase LpxJ for Secondary Fatty Acid Addition. 3001 28