Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma-induced GTPases are key to the protective immunity against microbial and viral pathogens. As yet, the cell interior has been regarded as the exclusive residence of these proteins. Here we show that a member of this group, human guanylate binding protein-1 (hGBP-1), is secreted from cells. Secretion occurred in the absence of a leader peptide via a nonclassical, likely ABC transporter-dependent, pathway, was independent of hGBP-1 GTPase activity and isoprenylation, and did not require additional interferon-gamma-induced factors. Interestingly, hGBP-1 was only secreted from endothelial cells but not from any of the nine different cell types tested. Clinically most important was the detection of significantly (P<0.001, Mann-Whitney U-test) increased hGBP-1 concentrations in the cerebrospinal fluid of patients with bacterial meningitis (n=32) as compared to control patients (n=74). In this first report of a secreted GTPase, we demonstrate that secreted hGBP-1 may be a useful surrogate marker for diagnosis of bacterial meningitis.
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PMID:Human guanylate binding protein-1 is a secreted GTPase present in increased concentrations in the cerebrospinal fluid of patients with bacterial meningitis. 1693 81

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is a major cause of death and disability all over the world. From perinatal period to adult, four common organisms responsible for most of the bacterial meningitis are Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenza and Staphylococcus aureus. As the disease is caused by more organisms, currently available vaccines for bacterial meningitis are specific and restricted to some of the serogroups or serotypes of each bacterium. In an effort to design common vaccine against bacterial meningitis, proteomes of the four pathogens were compared to extract seven common surface exposed ABC transporter proteins. Pro-Pred server was used to investigate the seven surface exposed proteins for promiscuous T-cell epitopes prediction. Predicted 22 T-cell epitopes were validated through published positive control, SYFPEITHI and immune epitope database to reduce the epitope dataset into seven. T-cell epitope 162-FMILPIFNV-170 of spermidine/putrescine ABC transporter permease (potH) protein was conserved across the four selected pathogens of bacterial meningitis. Hence, structural analysis was extended for epitope 162-FMILPIFNV-170. Crystal structures of HLA-DRB alleles were retrieved and structure of potH was modeled using Prime v3.0 for structural analysis. Computational docking of HLA-DRB alleles and epitope 162-FMILPIFNV-170 of potH was performed using Glide v5.7. RMSD and RMSF of simulation studies were analyzed by Desmond v3.2. The docking and simulation results revealed that the HLA-DRB-epitope complex was stable with interaction repressive function of HLA. Thus, the epitope would be ideal candidate for T-cell driven subunit vaccine design against bacterial meningitis.
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PMID:Computational approaches to identify common subunit vaccine candidates against bacterial meningitis. 2374 Mar 98