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)

The epidemiological situation of bacterial meningitis is increasing dramatically. There is no doubt that the lack of proper animal models has hampered the achievement of effective prophylactic and therapeutic means. We report the characterization of the experimental disease caused by Haemophilus influenzae type b (Hib) in mice, taking into account its importance as an etiological agent of such a type of meningitis. The high resistance of C57BL/6, CBA/ J and BALB/cJ mice to Hib infection was proven. LD50 of Hib using trypsin or iron dextran as virulence enhancement factors (VEF), both being similar and more than 1000 times lower than that without any VEF, were determined. Lesions of CNS compatible with meningitis were found in about one third of specimens. Hair bristling, conjunctivitis, diarrhea, depression and prostration were the most characteristic symptoms. The proportion of animals which die is highest on the first day, lower on the second and almost zero after 48 h of infection. Water and food intake was higher in control than in infected animals; nevertheless, there were no differences in body weight increase among the mice after 5 days post-infection. Microorganisms were isolated from CSF and blood after 6 h of infection and positive results remained according to the size of the inoculum. Despite the acuteness of the experimental disease, antibiotic treatment with internationally recommended drugs was shown to be effective. Similar results were achieved when hyperimmune serum vs. Hib was applied.
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PMID:Experimental infection by Haemophilus influenzae type b in inbred mice. 869 54

A 61-year-old male fell from a position 1 m high when building a house. An iron rod, which protruded upward from a solid base in cement, penetrated this patient's neck 15 cm to the head and was successfully extracted by himself. On admission, he complained of headache and vomiting. General examination disclosed nasal bleeding, intraoral bleeding, and L figured skin laceration in the left side of his neck at the level of the thyroid cartilage. Mild disorientation (JCS2) was noted. Otolaryngological examination disclosed hyperemia on the left side of the vocal cord as well as at the dome of the superior pharynx. Plain skull film disclosed pneumocephalus and that a piece of bone fragment of the planum sphenoidale had penetrated the brain. CT demonstrated air in the subarachnoid space, ventricular hemorrhage, intracerebral hematoma in the right frontal lobe, and subarachnoid hemorrhage in the anterior interhemispheric fissure. CAG detected neither cerebral vascular abnormalities nor cerebral aneurysm. While staying in our department, he developed mild fever and CSF rhinorrhea. The diagnosis of bacterial meningitis was made from the CSF finding and was well controlled with conservative therapy. CSF rhinorrhea stopped spontaneously with conservative treatment. Sagittal MRI continuously demonstrated contusional hematoma in the base of the right frontal lobe just above the fractured planum sphenoidale and genu of the corpus callosum following the course of the intracranially invading iron rod. The right CAG on Day 10 demonstrated vasospasm on the A1 and a 1 cm sized saccular cerebral aneurysm at the proximal right fronto-polar artery. CAG on Day 17 again showed the persistent presence of the aneurysm. For the purpose of preventing delayed rupture of the aneurysm, radical surgical treatment was planned. Microsurgical dissection disclosed that the aneurysm was located just behind the elevated fracture of the planum sphenoidale. Severe arachnoid adhesion was noted around the aneurysm. The aneurysm was successfully clipped with preservation of the parent artery without inducing new neurological deficits. From the general, otolaryngological, neuroradiological, and operative findings, this aneurysm was diagnosed as a traumatic cerebral artery aneurysm following the penetration of the skull base by the iron rod. The CAG performed at 8 months postoperatively demonstrated the patency of the parent artery and that there was no recurrence of the aneurysm. An unusual case of a traumatic cerebral artery aneurysm following the penetration of the skull base by an iron rod was thus reported.
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PMID:[A case of a traumatic anterior cerebral artery aneurysm following the penetration of the skull base by an iron rod]. 1039 43

To detect endogenous nitric oxide (NO) produced in a rat bacterial meningitis model, the authors applied an electron paramagnetic resonance (EPR) NO-trapping technique. Iron complex with N,N-diethyldithiocarbamate were used as a trapping agent. Experimental meningitis was induced by a mixture of lipopolysaccharide and interferon-gamma. Sequential changes of NO formation under meningitis were observed in rat brain tissue by using X-band (9 GHz) EPR spectroscopy, and endogenous NO was detected in the head of a living rat with a 700-MHz EPR system. Inducible NO synthase mRNA expression in the brain tissues also was proven by using a reverse transcriptase-polymerase chain reaction technique.
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PMID:Direct evidence of in vivo nitric oxide production and inducible nitric oxide synthase mRNA expression in the brain of living rat during experimental meningitis. 1056 63

Neisseria meningitidis, a causative agent of bacterial meningitis and septicemia, obtains transferrin-bound iron by expressing two outer membrane-located transferrin-binding proteins, TbpA and TbpB. A novel system was developed to investigate the interaction between Tbps and human transferrin. Copurified TbpA-TbpB, recombined TbpA-TbpB, and individual TbpA and TbpB were reconstituted into liposomes and fused onto an HPA chip (BIAcore). All preparations formed stable monolayers, which, with the exception of TbpB, could be regenerated by removing bound transferrin. The ligand binding properties of these monolayers were characterized with surface plasmon resonance and shown to be specific for human transferrin. Kinetic data for diferric human transferrin binding showed that recombined TbpA-TbpB had K(a) and K(d) values similar to those of copurified TbpA-TbpB. Individual TbpA and TbpB also displayed K(a) values similar to those of copurified TbpA-TbpB, but their K(d) values were one order of magnitude higher. Chemical cross-linking studies revealed that TbpA and TbpB, in the absence of human transferrin, formed large complexes with TbpA as the predominant species. Upon human transferrin binding, a complex was formed with a molecular mass corresponding to that of a TbpB-human transferrin heterodimer as well as a higher-molecular-mass complex of this heterodimer cross-linked to TbpA. This indicates that TbpA and TbpB form a functional meningococcal receptor complex in which there is cooperativity in the human transferrin binding kinetics. However, iron loss from the diferric human transferrin-TbpA-TbpB complex was not greater than that from human transferrin alone, suggesting that additional meningococcal transport components are involved in the process of iron removal.
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PMID:Meningococcal transferrin-binding proteins A and B show cooperation in their binding kinetics for human transferrin. 1566 36

Neisseria meningitidis, a causative agent of bacterial meningitis, obtains transferrin-bound iron by expressing two outer membrane located transferrin-binding proteins, TbpA and TbpB. TbpA is thought to be an integral outer membrane pore that facilitates iron uptake. Evidence suggests that TbpA is a useful antigen for inclusion in a vaccine effective against meningococcal disease, hence the identification of regions involved in ligand binding is of paramount importance to design strategies to block uptake of iron. The protein shares sequence and functional similarities to the Escherichia coli siderophore receptors FepA and FhuA, whose structures have been determined. These receptors are composed of two domains, a 22-stranded beta-barrel and an N-terminal plug region that sits within the barrel and occludes the transmembrane pore. A three-dimensional TbpA model was constructed using FepA and FhuA structural templates, hydrophobicity analysis and homology modelling. TbpA was found to possess a similar architecture to the siderophore receptors. In addition to providing insights into the highly immunogenic nature of TbpA and allowing the prediction of potentially important ligand-binding epitopes, the model also reveals a narrow channel through its entire length. The relevance of this channel and the spatial arrangement of external loops, to the mechanism of iron translocation employed by TbpA is discussed.
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PMID:Homology modelling of transferrin-binding protein A from Neisseria meningitidis. 1582 Sep 75

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.
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PMID:Structural basis for iron piracy by pathogenic Neisseria. 2232 95

Neisseria meningitidis, the causative agent of bacterial meningitis, acquires the essential element iron from the host glycoprotein transferrin during infection through a surface transferrin receptor system composed of proteins TbpA and TbpB. Here we present the crystal structures of TbpB from N. meningitidis in its apo form and in complex with human transferrin. The structure reveals how TbpB sequesters and initiates iron release from human transferrin.
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PMID:The structural basis of transferrin sequestration by transferrin-binding protein B. 2234 19

Neutrophil gelatinase-associated lipocalin (NGAL), an essential component of the antimicrobial innate immune system, is present in neutrophils and multiple other tissues. It prevents iron acquisition by microorganisms by sequestering iron-loaded bacterial siderophores. NGAL also modulates neutrophil functions. Its production is inducible following Toll-like receptor 4 activation and release of pro-inflammatory cytokines. NGAL is employed clinically in the diagnosis of acute kidney injury and may be useful in general in the differential diagnosis of a bacterial-mediated infectious process. Elevated levels of NGAL have been detected in the blood of patients with bacterial urinary tract infection, community-acquired pneumonia, sepsis, as well as in the cerebrospinal fluid and peritoneal fluid of patients with bacterial meningitis and peritonitis. Some bacteria have developed resistance to NGAL-mediated iron sequestration by production of modified siderophores that are not recognized by NGAL.
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PMID:Neutrophil gelatinase-associated lipocalin and innate immune responses to bacterial infections. 2571 57

Most bacterial small RNAs (sRNAs) are post-transcriptional regulators involved in adaptive responses, controlling gene expression by modulating translation or stability of their target mRNAs often in concert with the RNA chaperone Hfq. Neisseria meningitides, the leading cause of bacterial meningitis, is able to adapt to different host niches during human infection. However, only a few sRNAs and their functions have been fully described to date. Recently, transcriptional expression profiling of N. meningitides in human blood ex vivo revealed 91 differentially expressed putative sRNAs. Here we expanded this analysis by performing a global transcriptome study after exposure of N. meningitides to physiologically relevant stress signals (e.g. heat shock, oxidative stress, iron and carbon source limitation). and we identified putative sRNAs that were differentially expressed in vitro. A set of 98 putative sRNAs was obtained by analyzing transcriptome data and 8 new sRNAs were validated, both by Northern blot and by primer extension techniques. Deletion of selected sRNAs caused attenuation of N. meningitides infection in the in vivo infant rat model, leading to the identification of the first sRNAs influencing meningococcal bacteremia. Further analysis indicated that one of the sRNAs affecting bacteremia responded to carbon source availability through repression by a GntR-like transcriptional regulator. Both the sRNA and the GntR-like regulator are implicated in the control of gene expression from a common network involved in energy metabolism.
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PMID:Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia. 2595 Oct 61

Neonatal Meningitis Escherichia coli (NMEC) is one of the most common causes of neonatal bacterial meningitis in the US and elsewhere resulting in mortality or neurologic deficits in survivors. Large plasmids have been shown experimentally to increase the virulence of NMEC in the rat model of neonatal meningitis. Here, 9 ExPEC-like plasmids were isolated from NMEC and sequenced to identify the core and accessory plasmid genes of ExPEC-like virulence plasmids in NMEC and create an expanded plasmid phylogeny. Results showed sequenced virulence plasmids carry a strongly conserved core of genes with predicted functions in five distinct categories including: virulence, metabolism, plasmid stability, mobile elements, and unknown genes. The major functions of virulence-associated and plasmid core genes serve to increase in vivo fitness by adding multiple iron uptake systems to the genetic repertoire to facilitate NMEC's survival in the host's low iron environment, and systems to enhance bacterial resistance to host innate immunity. Phylogenetic analysis based on these core plasmid genes showed that at least two lineages of ExPEC-like plasmids could be discerned. Further, virulence plasmids from Avian Pathogenic E. coli and NMEC plasmids could not be differentiated based solely on the genes of the core plasmid genome.
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PMID:Genetic Characterization of ExPEC-Like Virulence Plasmids among a Subset of NMEC. 2680 Feb 68


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