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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparison of relative levels of autoantibodies (Abs) to both native (n) and denatured (d) DNA in the blood of 55 patients with tick-borne encephalitis (TBE) was carried out. 31% of patients with TBE was shown to have an increased level Abs to nDNA and 40% of patients demonstrate increased level of Abs to dDNA. The percent of TBE patients with increased concentration of anti-nDNA Abs higher then that in patients with multiple sclerosis (18%) and some other autoimmune diseases (6-18%), but comparable with that for patients with systemic lupus erythematosus (38%) and polymyositis (42%). In contrast to patients with systemic lupus erythematosus and multiple sclerosis, the level of Abs to nDNA in patients with TBE is higher than the level of Abs to dDNA. Correlation coefficients of Ab levels to both n- and dDNA were estimated for group of patients in whole and for separate subgroups with different type of disease (temperature reaction, feverishness and meningitis). Analysis of correlation between titres of anti-DNA Abs and three standard biochemical markers of TBE (activity of aspartate- and alanine-aminotransferases, and concentration of whole bilirubin) for 22 patients with TBE was carried out. Statistically significant correlation was revealed only between the level of Abs to nDNA and activities of aspartate- and alanine-aminotransferases, correlation coefficients are equal to +0.44 and +0.48, respectively.
Mol Biol (Mosk)
PMID:[Antibodies to DNA in the blood of patients with tick-borne encephalitis]. 1545 45

Patterns of genetic diversity within populations of human pathogens, shaped by the ecology of host-microbe interactions, contain important information about the epidemiological history of infectious disease. Exploiting this information, however, requires a systematic approach that distinguishes the genetic signal generated by epidemiological processes from the effects of other forces, such as recombination, mutation, and population history. Here, a variety of quantitative techniques were employed to investigate multilocus sequence information from isolate collections of Neisseria meningitidis, a major cause of meningitis and septicemia world wide. This allowed quantitative evaluation of alternative explanations for the observed population structure. A coalescent-based approach was employed to estimate the rate of mutation, the rate of recombination, and the size distribution of recombination fragments from samples from disease-associated and carried meningococci obtained in the Czech Republic in 1993 and a global collection of disease-associated isolates collected globally from 1937 to 1996. The parameter estimates were used to reject a model in which genetic structure arose by chance in small populations, and analysis of molecular variation showed that geographically restricted gene flow was unlikely to be the cause of the genetic structure. The genetic differentiation between disease and carriage isolate collections indicated that, whereas certain genotypes were overrepresented among the disease-isolate collections (the "hyperinvasive" lineages), disease-associated and carried meningococci exhibited remarkably little differentiation at the level of individual nucleotide polymorphisms. In combination, these results indicated the repeated action of natural selection on meningococcal populations, possibly arising from the coevolutionary dynamic of host-pathogen interactions.
Mol Biol Evol 2005 Mar
PMID:The influence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis. 1553 8

We determined the molecular sequence of monoclonal antibodies (mAbs) to serogroups B and C capsular polysaccharides (PS) of Neisseria meningitidis. N. meningitidis infections are a leading cause of bacterial septicemia and meningitis in humans. Antibodies to PS are fundamental to host defense and diagnostics. The polysaccharide capsule of group B N. meningitidis is poorly immunogenic and thus is an important model for studying pathogen-host co-evolution through understanding the molecular basis of the host immune response. We used a modified reverse-transcriptase PCR to amplify and sequence the V-genes of murine hybridomas produced against types B and C capsular PS. Databank analysis of the sequences encoding the V-genes of type C capsular PS mAb, 4-2-C, reveal that heavy chain alleles are recurrently used to encode this specificity in mice. Interestingly, a V-gene from the same germline family also encodes the V-domain of mAbs 2-2-B, which targets the antigenically distinct serogroup B capsular PS. Somatic mutation, junctional diversity and alternative light chains collectively impart the specificity for these serologically distinct epitopes. Knowledge of the specific immunoglobulin genes used to target common bacterial virulence factors may lead to insights on pathogen-host co-evolution, and the potential use of this information in pre-symptomatic diagnosis is discussed.
Mol Immunol 2005 Feb
PMID:Molecular analysis of monoclonal antibodies to group variant capsular polysaccharide of Neisseria meningitidis: recurrent heavy chains and alternative light chain partners. 1558 22

Neisseria meningitidis is a human pathogen, which is a major cause of sepsis and meningitis. The bacterium colonizes the upper respiratory tract of approximately 10% of humans where it lives as a commensal. On rare occasions, it crosses the epithelium and reaches the bloodstream causing sepsis. From the bloodstream it translocates the blood-brain barrier, causing meningitis. Although all strains have the potential to cause disease, a subset of them, which belongs to hypervirulent lineages, causes disease more frequently than others. Recently, we described NadA, a novel antigen of N. meningitidis, present in three of the four known hypervirulent lineages. Here we show that NadA is a novel bacterial invasin which, when expressed on the surface of Escherichia coli, promotes adhesion to and invasion into Chang epithelial cells. Deletion of the N-terminal globular domain of recombinant NadA or pronase treatment of human cells abrogated the adhesive phenotype. A hypervirulent strain of N. meningitidis where the nad A gene was inactivated had a reduced ability to adhere to and invade into epithelial cells in vitro. NadA is likely to improve the fitness of N. meningitidis contributing to the increased virulence of strains that belong to the hypervirulent lineages.
Mol Microbiol 2005 Feb
PMID:Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells. 1566 Sep 96

Cryptococcus neoformans is the leading cause of fungal meningitis in humans. Production of a polysaccharide capsule is a key virulence property for the fungus and capsule synthesis is regulated by iron levels. Given that iron acquisition is an important aspect of virulence for many pathogens, we employed serial analysis of gene expression (SAGE) to examine the transcriptome under iron-limiting and iron-replete conditions. Initially, we demonstrated by SAGE and Northern analysis that iron limitation results in an elevated transcript level for the CAP60 gene that is required for capsule production. We also identified genes encoding putative components for iron transport and homeostasis, including the FTR1 (iron permease) gene, with higher transcript levels in the low-iron condition. An FTR1 disruption mutant grows more slowly than wild-type cells in low-iron medium, and shows delayed growth and altered capsule regulation in iron-replete medium. Iron deprivation also resulted in elevated SAGE tags for putative extracellular mannoproteins and the GPI8 gene encoding a glycosylphosphatidylinositol (GPI) transamidase. The GPI8 gene appears to be essential while disruption of the CIG1 gene encoding a mannoprotein resulted in impaired growth in low-iron medium and altered capsule response to the iron-replete condition. Additionally, we found that iron-replete conditions led to elevated transcripts for genes for iron storage, nitrogen metabolism, glycolysis, mitochondrial function, lipid metabolism and calmodulin-calcineurin signalling. Overall, these studies provide the first view of the C. neoformans transcriptional response to different iron levels.
Mol Microbiol 2005 Mar
PMID:Iron-regulated transcription and capsule formation in the fungal pathogen Cryptococcus neoformans. 1572 May 53

Group B Streptococcus (GBS) is a common constituent of the vaginal microflora, but its transmission to newborns can cause life-threatening sepsis, pneumonia and meningitis. Energy metabolism of this opportunist pathogen has been deduced to be strictly fermentative. We discovered that GBS undergoes respiration metabolism if its environment supplies two essential respiratory components: quinone and haem. Respiration metabolism led to significant changes in growth characteristics, including a doubling of biomass and an altered metabolite profile under the tested conditions. The GBS respiratory chain is inactivated by: (i) withdrawing haem and/or quinone, (ii) treating cultures with a respiration inhibitor or (iii) inactivating the cydA gene product, a subunit of cytochrome bd quinol oxidase, in all cases resulting in exclusively fermentative growth. cydA inactivation reduced GBS growth in human blood and strongly attenuated virulence in a neonatal rat sepsis model, suggesting that the animal host may supply the components that activate GBS respiration. These results suggest a role of respiration metabolism in GBS dissemination. Our findings show that environmental factors can increase the flexibility of GBS metabolism by activating a newly identified respiration chain. The need for two environmental factors may explain why GBS respiration metabolism was not found in previous studies.
Mol Microbiol 2005 Apr
PMID:Respiration metabolism of Group B Streptococcus is activated by environmental haem and quinone and contributes to virulence. 1581 41

Group B streptococci (GBS) are the principal causal agents of human neonatal pneumonia, sepsis and meningitis. We had previously described the existence of a eukaryotic-type serine/threonine kinase (Stk1) and phosphatase (Stp1) in GBS that regulate growth and virulence of the pathogen. Our previous results also demonstrated that these enzymes reversibly phosphorylated an inorganic pyrophosphatase. To understand the role of these eukaryotic-type enzymes on growth of GBS, we assessed the stk1-mutants for auxotrophic requirements. In this report, we describe that in the absence of the kinase (Stk1), GBS are attenuated for de novo purine biosynthesis and are consequently growth arrested. During growth in media lacking purines, the intracellular G nucleotide pools (GTP, GDP and GMP) are significantly reduced in the Stk1-deficient strains, while levels of A nucleotides (ATP, ADP and AMP) are marginally increased when compared with the isogenic wild-type strain. We provide evidence that the reduced pools of G nucleotides result from altered activity of the IMP utilizing enzymes, adenylosuccinate synthetase (PurA) and IMP dehydrogenase (GuaB) in these strains. We also demonstrate that Stk1 and Stp1 reversibly phosphorylate and consequently regulate PurA activity in GBS. Collectively, these data indicate the novel role of eukaryotic-type kinases in regulation of metabolic processes such as purine biosynthesis.
Mol Microbiol 2005 Jun
PMID:Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae. 1588 24

Noninvasive real-time in vivo bioluminescent imaging was used to assess the spread of Streptococcus pneumoniae throughout the spinal cord and brain during the acute stages of bacterial meningitis. A mouse model was established by lumbar (LP) or intracisternal (IC) injection of bioluminescent S. pneumoniae into the subarachnoid space. Bacteria replicated initially at the site of inoculation and spread progressively from the spinal cord to the brain or from the brain down to the cervical part of the spinal column and to the lower vertebral levels. After 24 hr, animals showed strong bioluminescent signals throughout the spinal canal, indicating acute meningitis of the intracranial and intraspinal meninges. A decline in bacterial cell viability, as judged by a reduction in the bioluminescent signal, was observed over time in animals treated with ceftriaxone, but not in untreated groups. Mice treated with the antibiotic survived infection, whereas all mice in untreated groups became moribund, first in the IC group then in the LP group. No untreated animal survived beyond 48 hr after induction of infection. Colony counts of infected cerebrospinal fluid (CSF) correlated positively with bioluminescent signals. This methodology is especially appealing because it allows detecting infected mice as early as 3 hr after inoculation, provide temporal, sequential, and spatial distribution of bacteria within the brain and spinal cord throughout the entire disease process and the rapid monitoring of treatment efficacy in a nondestructive manner. Moreover, it avoids the need to sacrifice the animals for CSF sampling and the potential manipulative damage that can occur with other conventional methods.
Mol Imaging
PMID:Noninvasive monitoring of pneumococcal meningitis and evaluation of treatment efficacy in an experimental mouse model. 1610 11

Enterobacter sakazakii has been implicated in a several form of neonatal meningitis with a high mortality rate. In the present study, the species-specific PCR and oligonucleotide array assays were developed to detect the 16S-23S rDNA internal transcribed spacer (ITS) of E. sakazakii. Two pairs of specific PCR primers and 10 oligonucleotide probes were designed by sequencing the ITS of six strains of E. sakazakii and BLAST of GenBank. The specificity and efficiency of the PCR and oligonucleotide array methods were tested against a panel of numerous strains from 88 different bacterial strains. All of the E. sakazakii strains generated positive signal, and no cross-reaction was observed with non-E. sakazakii strains in the PCR and oligonucleotide array detections based on ITS sequences. Sensitivity of the detections is 1.3 CFU/100 g infant formula with the selective enrichment. Both of the PCR and oligonucleotide array procedures take only 48 h including the enrichment culture, whereas the conventional methods required at least 5 days. This study demonstrated that both of the pathogenic detections are time-saved and reliable.
Mol Cell Probes 2006 Feb
PMID:PCR and oligonucleotide array for detection of Enterobacter sakazakii in infant formula. 1622 71

Group B streptococci (GBS), mainly serotype III, are the major cause of neonatal pneumonia, sepsis and meningitis. Virulence potential of GBS strains may determine the outcome of host colonization or infection. Because the lung constitutes a first step in GBS systemic invasion processes, we investigated the adherence and invasion mechanisms of GBS-III clinical isolates to non-polarized human bronchial epithelial 16 HBE 14o- cell line. The presence of genotypic 162-kb and 183-kb virulence markers in all strains was also examined by PFGE. The 162-kb fragment was detected in both liquor (GBS-III 90356) and vagina (GBS-III 39A) isolates, while 183-kb fragment was only observed in strains (GBS-III 39A, 89A, and 80340) isolated from vagina of asymptomatic carriers. The actin-dependent ability to internalize within non-polarized epithelial respiratory cells was demonstrated only by GBS-III clinical isolates presenting the 162-kb virulence marker. GBS-III 39A strain isolated from vagina exhibiting both 183-kb and 162-kb fragments showed a more efficient adherence and invasion properties than GBS-III 90356 isolated from liquor (P<0.001). Our data suggest the expression of additional bacterial virulence factors that may favor adherence and survival to non-polarized respiratory epithelial cells with consequent development of systemic diseases by GBS-III, including some strains isolated from asymptomatic carriers.
Int J Mol Med 2006 Mar
PMID:Intracellular viability in human non-polarized respiratory epithelial 16 HBE 14o- cells by group B Streptococcus serotype III clinical isolates presenting 162-kb and 183-kb virulence markers. 1646 4


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