Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TB10.4 is a newly identified antigen of Mycobacterium tuberculosis recognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization with Mycobacterium bovis BCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 peptide was identified as an immunodominant CD4+ T-cell epitope for H-2d mice. Since recent results, as well as the present study, have raised interest in TB10.4 as a subunit vaccine, we analyzed immune responses induced by this antigen delivered by a new vector, the adenylate cyclase (CyaA) of Bordetella pertussis. CyaA is able to target dendritic cells and to deliver CD4+ or CD8+ T-cell epitopes to the major histocompatibility complex class II/I molecule presentation pathways, triggering specific Th1 or cytotoxic T-lymphocyte (CTL) responses. Several CyaA harboring either the entire TB10.4 protein or various subfragments containing the TB10.4:20-28 CTL epitope were shown to induce TB10.4-specific Th1 CD4+ and CD8+ T-cell responses. However, none of the recombinant CyaA, injected in the absence of adjuvant, was able to induce protection against M. tuberculosis infection. In contrast, TB10.4 protein administered with a cocktail of strong adjuvants that triggered a strong Th1 CD4+ T-cell response induced significant protection against M. tuberculosis challenge. These results confirm the potential value of the TB10.4 protein as a candidate vaccine and show that the presence of high frequencies of CD4+ T cells specific to this strong immunogen correlates with protection against M. tuberculosis infection.
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PMID:High frequency of CD4+ T cells specific for the TB10.4 protein correlates with protection against Mycobacterium tuberculosis infection. 1671 70

The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.
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PMID:Antimicrobial peptides in the airway. 1690 21

Polymerase chain reaction protocols are now available for the diagnosis of all of the major bacterial respiratory tract pathogens. Molecular techniques are also being used to determine the susceptibility of Streptococcus pneumoniae and Mycobacterium tuberculosis. In addition, polymerase chain reaction-based diagnosis will find a place in the investigation of the epidemiology of some pathogens such as Bordetella pertussis and Chlamydia pneumoniae. The added sensitivity will allow the detection of mild or asymptomatic cases or carriers who may play a role in sustaining the pathogen in the community.
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PMID:New polymerase chain reaction-based diagnostic techniques for bacterial respiratory infection. 1703 78

The genetically detoxified Bordetella pertussis adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with Mycobacterium tuberculosis antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.
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PMID:Enhanced ex vivo stimulation of Mycobacterium tuberculosis-specific T cells in human immunodeficiency virus-infected persons via antigen delivery by the Bordetella pertussis adenylate cyclase vector. 1752 28

More than 4 million deaths per year are due to respiratory diseases. Although licensed vaccines are available, bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Bordetella pertussis and Neisseria meningiditis, among others, continue to be the major agents of diseases in young children, the elderly and/or immunocompromized individuals. Following respiratory tract infection, some microorganisms may also invade the epithelial tissue, achieving systemic circulation and/or other organs. Nasal administration of different antigen formulations has shown promising results in the induction of immune responses and the defeat of the pathogens at the site of infection. This review will focus on the main nasal vaccine strategies and technologies being investigated against the most common infections caused by respiratory bacteria.
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PMID:Intranasal vaccines for protection against respiratory and systemic bacterial infections. 1754 56

Bordetella pertussis is known to be a genotypically homogeneous pathogen but the extent of homogeneity at the genomic level is unknown. A currently circulating B. pertussis isolate from Australia was compared with the genome-sequenced Tohama I strain isolated in Japan in the 1950s from a distantly related lineage. Microarray-based comparative genome sequencing (CGS) was used to detect single nucleotide polymorphisms (SNPs) in a total of 1.4 Mb of the 4.09 Mb genome, including 1012 coding-regions, 217 pseudogenes and 268 intergenic regions. The CGS analysis, followed by validation using real-time PCR and DNA sequencing, identified 70 SNPs and five 1-3 bp indels, giving an overall frequency of base changes of 1 per 20 kb. Thirty-two of the 56 SNPs in coding regions were non-synonymous, including five located in virulence-associated genes. The data also allowed us to compare genomic diversity with other "clonal" human pathogens such as Mycobacterium tuberculosis and Yersinia pestis, showing that B. pertussis may be one of the least variable pathogenic bacterial species.
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PMID:Genome-wide analysis of single nucleotide polymorphisms in Bordetella pertussis using comparative genomic sequencing. 1879 49

Mucosal vaccination offers attractive advantages to conventional systemic vaccination, such as higher levels of antibodies and protection at the airway surface. This review gives an overview of recent experimental and clinical data on nasal, oral and sublingual vaccines against bacterial respiratory pathogens, such as Streptococcus pneumoniae , Haemophilus influenzae , Neisseria meningitidis , Moraxella catarrhalis , Bordetella pertussis , Pseudomonas aeruginosa and Mycobacterium tuberculosis . Subsequently, we discuss further vaccine development that opens the focus to clinical use.
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PMID:Mucosal vaccination against bacterial respiratory infections. 1884 98

Mycobacterium bovis BCG has long been investigated as a candidate for heterologous antigen presentation. We have previously described an rBCG-Pertussis that confers protection against challenge with Bordetella pertussis in neonate and adult mice. In order to obtain stable expression in vivo, we constructed an unmarked BCG lysine auxotrophic and a complementation vector containing the lysine and the genetically detoxified S1 pertussis toxin genes, both under control of the same promoter. Complemented BCG-Delta lysine growth and expression of the pertussis antigen were stable, without the use of an antibiotic marker. Our results show that the complemented rBCG-Delta lysA-S1PT-lysA(+)(kan(-)), which is now suitable to be evaluated in clinical trials, maintains similar characteristics of the original rBCG-pNL71S1PT strain, such as the antigen expression level, cellular immune response and protection against the same model challenge in neonatal-immunized mice.
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PMID:Construction of an unmarked recombinant BCG expressing a pertussis antigen by auxotrophic complementation: protection against Bordetella pertussis challenge in neonates. 1978 11

At 14:28 on 12 May 2008, Sichuan Province of China suffered a devastating earthquake measuring 8.0 on the Richter scale with more than 80 000 human lives lost and millions displaced. With inadequate shelter, poor access to health services, and disrupted ecology, the survivors were at enormous risk of infectious disease outbreaks. This work, believed to be unprecedented, was carried out to contain a possible outbreak through onsite monitoring of airborne biological agents in the high-risk areas. In such a mission, a mobile laboratory was developed using a customized vehicle along with state-of-art bioaerosol and molecular equipment and tools, and deployed to Sichuan 11 days after the earthquake. Using a high volume bioaerosol sampler (RCS High Flow) and Button Inhalable Aerosol Sampler equipped with gelatin filters, a total of 55 air samples, among which are 28 filter samples, were collected from rubble, medical centers, and camps of refugees, troops and rescue workers between 23 May and 9 June, 2008. After pre-treatment of the air samples, quantitative polymerase chain reaction (qPCR), gel electrophoresis, limulus amebocyte lysate (LAL) assay and enzyme-linked immunosorbent assay (ELISA) were applied to detect infectious agents and to quantify environmental toxins and allergens. The results revealed that, while high levels of endotoxin (180 approximately 975 ng/m3) and (1,3)-beta-d-glucans (11 approximately 100 ng/m3) were observed, infectious agents such as Bacillus anthracis, Bordetella pertussis, Neisseria meningitidis, Mycobacterium tuberculosis, influenza A virus, bird flu virus (H5N1), enteric viruses, and Meningococcal meningitis were found below their detection limits. The total bacterial concentrations were found to range from 250 to 2.5 x 10(5) DNA copies/L. Aspergillus fumigatus (Asp f 1) and dust mite allergens (Der p 1 and Der f 1) were also found below their detection limits.
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PMID:Onsite infectious agents and toxins monitoring in 12 May Sichuan earthquake affected areas. 1989 May 56

Changes in effective population size impinge on patterns of molecular evolution. Notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. This prediction has been validated empirically for several endosymbiont and island taxa. Here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidates for reduced effective population size: Bacillus anthracis, Bordetella parapertussis, Mycobacterium leprae, Salmonella enterica typhi, Shigella spp., and Yersinia pestis. Using closely related genomes to analyze substitution rate dynamics across six phylogenetically independent bacterial clades, we demonstrate that relative rates of coding sequence evolution are biased according to gene functional category. Notably, genes that buffer against slightly deleterious mutations, such as chaperones, experience stronger rate accelerations than other functional classes at both nonsynonymous and synonymous sites. Although theory predicts altered evolutionary dynamics for buffer loci in the face of accumulating deleterious mutations, to observe even stronger rate accelerations is surprising. We suggest that buffer loci experience elevated substitution rates because the accumulation of deleterious mutations in the remainder of the genome favors compensatory substitutions in trans. Critically, the hyper-acceleration is evident across phylogenetically independent clades, supporting the hypothesis that reductions in effective population size predictably induce epistatic responses in genes that buffer against slightly deleterious mutations.
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PMID:Function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size. 2134 81


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