共查询到20条相似文献,搜索用时 15 毫秒
1.
Guangchun Bai Damen D. Schaak & Kathleen A. McDonough 《FEMS immunology and medical microbiology》2009,55(1):68-73
Adenosine 3',5'-cyclic monophosphate (cAMP)-mediated signal transduction is common in both prokaryotes and eukaryotes, and several bacterial pathogens modulate cAMP signaling pathways of their mammalian hosts during infection. In this study, cAMP levels associated with Mycobacterium tuberculosis and Mycobacterium bovis BCG were measured during macrophage infection. cAMP levels within both bacteria increased c . 50-fold during infection of J774.16 macrophages, relative to the cAMP levels within bacteria incubated in tissue culture media alone. cAMP levels also increased within the macrophage cytoplasm upon uptake of live, but not dead, mycobacteria. The presence of albumin in the absence of oleic acid significantly decreased cAMP secretion and production by both M. tuberculosis and M. bovis BCG. These results suggest that cAMP signaling plays a role in the interaction of tuberculosis-complex mycobacteria with macrophages during infection, and that albumin may be a physiological indicator differentiating host environments during infection. 相似文献
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Influence of BCG vaccine strain on the immune response and protection against tuberculosis 总被引:3,自引:0,他引:3
The Bacille Calmette–Guérin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifying BCG strains with superior protection would have a dramatic effect on tuberculosis control at a population level: a small increment in protection provided by BCG immunization will prevent large numbers of cases of severe tuberculosis and deaths, particularly in children. 相似文献
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Bosco Christiano Maciel da Silva Maria Fernanda Rios Grassi Raimundo Coutinho Rita Elizabeth Moreira Mascarenhas Viviana Nilla Olavarria Adriana Coutinho-Borgo Jorge Kalil Edecio Cunha Neto Simone Gon?alves Fonseca 《Memórias do Instituto Oswaldo Cruz》2014,109(8):999-1004
The interferon (IFN)-γ response to peptides can be a useful diagnostic marker of
Mycobacterium tuberculosis (MTB) latent infection. We identified promiscuous and
potentially protective CD4+ T-cell epitopes from the most conserved
regions of MTB antigenic proteins by scanning the MTB antigenic proteins GroEL2,
phosphate-binding protein 1 precursor and 19 kDa antigen with the TEPITOPE algorithm.
Seven peptide sequences predicted to bind to multiple human leukocyte antigen
(HLA)-DR molecules were synthesised and tested with IFN-γ enzyme-linked immunospot
(ELISPOT) assays using peripheral blood mononuclear cells (PBMCs) from 16 Mantoux
tuberculin skin test (TST)-positive and 16 TST-negative healthy donors. Eighty-eight
percent of TST-positive donors responded to at least one of the peptides, compared to
25% of TST-negative donors. Each individual peptide induced IFN-γ production by PBMCs
from at least 31% of the TST-positive donors. The magnitude of the response against
all peptides was 182 ± 230 x 106 IFN-γ spot forming cells (SFC) among
TST-positive donors and 36 ± 62 x 106 SFC among TST-negative donors (p =
0.007). The response to GroEL2 (463-477) was only observed in the TST-positive group.
This combination of novel MTB CD4 T-cell epitopes should be tested in a larger cohort
of individuals with latent tuberculosis (TB) to evaluate its potential to diagnose
latent TB and it may be included in ELISPOT-based IFN-γ assays to identify
individuals with this condition. 相似文献
4.
Guoqiang Zhang # Lingxia Zhang # Mingcheng Zhang Linlin Pan Fengyu Wang Jun Huang Guoli Li Jun Yu Songnian Hu* CAS Key Laboratory of Genome Sciences Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing China Graduate University of Chinese Academy of Sciences Beijing The Second Hospital Affiliated to the General Hospital of the People’s Liberation Army Beijing China. 《基因组蛋白质组与生物信息学报(英文版)》2009,7(3):107-115
Purified protein derivative (PPD) skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tuberculosis infection and Bacille Calmette-Guerin (BCG) vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames (ORFs) based on the genome sequences of M. tuberculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stim... 相似文献
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mpt64-卡介苗重组疫苗的构建、免疫原性及抗结核作用 总被引:1,自引:0,他引:1
通过基因工程重组技术将结核分枝杆菌保护性抗原MPT64的编码基因与穿梭质粒载体pYUB295重组,采用电穿孔技术将重组质粒导入到卡介苗中,应用聚合酶链反应(PCR)扩增、聚丙烯酰胺凝胶电泳(PAGE)对mpt64-卡介苗重组疫苗鉴定:成功地构建了MPT64基因pYUB295重组质粒,MPT64蛋白在卡介苗中能分泌表达.... 相似文献
8.
近年来,结核的发病率又呈上升趋势,传统的结核疫苗已无法起到有效的保护作用。结核分枝杆菌分泌蛋白由于具有良好的免疫保护性因而备受关注。结核分泌蛋白TB10.4是免疫主导的蛋白,能够激发有效的免疫反应,因而成为研究结核新疫苗靶抗原之一。本文就近几年结核分枝杆菌TB10.4的相关研究作一综述。 相似文献
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The tuberculosis (TB) vaccine strain Mycobacterium bovis BCG is unable to utilise alanine and this deficiency is thought to inhibit the growth of the vaccine in vivo and limit vaccine efficacy. In this report we demonstrate that L-alanine catabolism can be conferred on BCG by introduction of the gene encoding L-alanine dehydrogenase (Ald) of Mycobacterium tuberculosis. Restoration of Ald activity did not change the in vivo growth of BCG in macrophages or mice, and protection against aerosol M. tuberculosis infection was not altered by addition of ald to the BCG vaccine. These results demonstrate that the inability to utilise L-alanine is not a contributing factor to the attenuated phenotype of BCG and does not influence the protective efficacy of the vaccine against TB. 相似文献
11.
Manaswini Jagadeb Surya Narayan Rath 《Journal of biomolecular structure & dynamics》2019,37(13):3388-3398
The emergence of multidrug-resistant Mycobacterium tuberculosis (M.tb) has become one of the major hurdles in the treatment of tuberculosis (TB). Drug-resistant M.tb has evolved with various strategies to avoid killing by the anti-tubercular drugs. Thus, there is a rising need to develop effective anti-TB drugs to improve the treatment of these strains. Traditional drug design approach has earned little success due to time and the cost involved in the process of development of anti-infective drugs. Numerous reports have demonstrated that several mutations in the drug target sites cause emergence of drug-resistant M.tb strains. In this study, we performed computational mutational analysis of M.tb inhA, fabD, and ahpC genes, which are the primary targets for first-line isoniazid (INH) drug. In silico virtual drug screening was performed to identify the potent drugs from a ChEMBL compound library to improve the treatment of INH-resistant M.tb. Further, these compounds were analyzed for their binding efficiency against active drug binding cavity of M.tb wild-type and mutant InhA, FabD and AhpC proteins. The drug efficacy of predicted lead compounds was verified by molecular docking using M.tb wild-type and mutant InhA, FabD and AhpC protein template models. Different in silico and pharmacophore analysis predicted three potent lead compounds with better drug-like properties against both M.tb wild-type and mutant InhA, FabD, and AhpC proteins as compared to INH drug, and thus may be considered as effective drugs for the treatment of INH-resistant M.tb strains. We hypothesize that this work may accelerate drug discovery process for the treatment of drug-resistant TB.
Communicated by Ramaswamy H. Sarma 相似文献
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Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens causing tuberculosis (TB), a devastating infectious disease responsible for the highest human mortality and morbidity. The emergence of drug-resistant strains of the pathogen has increased the burden of TB tremendously and new therapeutics to overcome the problem of drug resistance are urgently needed. Metabolism of Mtb and its interactions with the host is important for its survival and virulence; this is an important topic of research where there is growing interest in developing new therapies and drugs that target these interactions and metabolism of the pathogen during infection. Mtb adapts its metabolism in its intracellular niche and acquires multiple nutrient sources from the host cell. Carbon metabolic pathways and fluxes of Mtb has been extensively researched for over a decade and is well-defined. Recently, there has been investigations and efforts to measure metabolism of nitrogen, which is another important nutrient for Mtb during infection. This review discusses our current understanding of the central carbon and nitrogen metabolism, and metabolic fluxes that are important for the survival of the TB pathogen. 相似文献
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Pulsed field gel electrophoresis of representatives of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains 总被引:1,自引:0,他引:1
Anne Varnerot Françoise Clément Marina Gheorghiu Véronique Vincent-Lévy-Frébault 《FEMS microbiology letters》1992,98(1-3):155-160
Abstract Using field inversion gel electrophoresis (FIGE), different Mycobacterium tuberculosis strains, such as phage prototypes, exhibit different DNA restriction patterns which are easy to compare. Virulent and avirulent variants of M. tuberculosis H37, as well as daughter strains of M. bovis BCG, display characteristic DNA profiles. BCG strains isolated from suppurative adenitis following vaccination of French patients showed patterns identical to the BCG Pasteur strain used for vaccination. These results demonstrate that FIGE of DNA restriction fragments generated by Dra I represents a suitable technique for the analysis of mycobacteria at a genomic level. The Dra I profiles allow the differentiation and precise identification of the BCG Pasteur, Glaxo, Russian and Japanese strains. 相似文献
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Several enzymes involved in central carbon metabolism and gluconeogenesisplay a critical role in survival and pathogenesis of Mycobacterium tuberculosis (Mtb). The only known functional fructose 1,6-bisphosphatase (FBPase) in Mtb is encoded by the glpX gene and belongs to the Class II sub-family of FBPase. We describe herein the generation of a ΔglpX strain using homologous recombination. Although the growth profile of ΔglpX is comparable to that of wild type Mtb when grown on the standard enrichment media, its growth is dysgonic with individual gluconeogenic substrates such as oleic acid, glycerol and acetate. In mice lung CFU titers of ΔglpX were 2–3 log10 lower than the wild-type Mtb strain. The results indicate that glpX gene encodes a functional FBPase and is essential for both in vitro and in vivo growth and survival of Mtb. Loss of glpX results in significant reduction of FBPase activity but not complete abolition. These findings verify that the glpX encoded FBPase II in Mtb can be a potential target for drug discovery. 相似文献
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结核分枝杆菌(Mycobacterium tuberculosis,MTB)是一种典型的胞内致病菌,巨噬细胞是MTB在体内的主要宿主细胞。巨噬细胞具有强大的吞噬功能,在机体固有免疫和适应性免疫中均发挥着重要作用,可有效保护宿主免受结核分枝杆菌的感染。MTB在与宿主巨噬细胞的长期相互作用过程中,逐渐形成多种逃避杀灭的有效策略,得以在宿主体内存活并增殖。该文从巨噬细胞抗MTB感染及MTB逃避巨噬细胞杀灭两个方面综述国内外的研究进展。 相似文献
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One of the challenges faced by Mycobacterium tuberculosis (M. tuberculosis) in dormancy is hypoxia. DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes. In this study, we have used DosR regulon proteins of M. tuberculosis H37Rv as the query set and performed a comprehensive homology search against the non-redundant database. Homologs were found in environmental mycobacteria, environmental bacteria and archaebacteria. Analysis of genomic context of DosR regulon revealed that they are distributed as nine blocks in the genome of M. tuberculosis with many transposases and integrases in their vicinity. Further, we classified DosR regulon proteins into eight functional categories. One of the hypothetical proteins Rv1998c could probably be a methylisocitrate lyase or a phosphonomutase. Another hypothetical protein, Rv0572 was found only in mycobacteria. Insights gained in this study can potentially aid in the development of novel therapeutic interventions. 相似文献
18.
Bruna Daniella Souza Silva Daniela Graner Schuwartz Tannus-Silva Marcelo Fouad Rabahi Andre Kipnis Ana Paula Junqueira-Kipnis 《Memórias do Instituto Oswaldo Cruz》2014,109(1):29-37
Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction
of articular cartilage and bone damage. The chronic treatment of RA patients causes a
higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of
the world’s population is latently infected (LTBI) with Mycobacterium
tuberculosis (Mtb). The tuberculin skin test is used to identify
individuals LTBI, but many studies have shown that this test is not suitable for RA
patients. The goal of this work was to test the specific cellular immune responses to
the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA
patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17
and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in
RA patients candidates for tumour necrosis factor-α blocker treatment. Our results
demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and
HspX. Patients were followed up over two years and 14.3% developed active TB. After
the development of active TB, RA patients had increased numbers of Th17 and Treg
cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen
assay can be used as a diagnostic test to identify LTBI RA patients. 相似文献
19.
通过比较基因组学的方法研究发现,牛分支杆菌与肺结核杆菌基因组的同源性为99.95%,但在牛分枝杆菌基因组中有11个缺失区,大小从1kb到12.7kb,遗传信息的缺失引起牛分枝杆菌的基因组减小;牛分枝杆菌与肺结核分枝杆菌H37Rv间存在着2437个单核苷酸多态性(SNPs),与肺结核分枝杆菌CDC1551间存在着2423个单核苷酸多态性(SNPs),牛分支杆菌与肺结核分枝杆菌在编码细胞壁和分泌蛋白上变异程度也是巨大的。研究结果揭示了牛分支杆菌与肺结核分枝杆菌的遗传关系,为研究分支杆菌疫苗和诊断试剂提供理论依据,对牛肺结核病的防治有着非常重要的意义。 相似文献
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Introduction of 65 kDa antigen of Mycobacterium tuberculosis to cancer cells enhances anti-tumor effect of BCG therapy 总被引:2,自引:0,他引:2
Hara I Sato N Miyake H Muramaki M Hikosaka S Kamidono S 《Microbiology and immunology》2004,48(4):289-295
Bacillus Calmette Guerin (BCG) immunotherapy has anti-tumorigenic effects against bladder cancer. To improve the efficacy of BCG therapy, we introduced the gene encoding the 65 kDa heat shock protein (hsp) of Mycobacterium tuberculosis into a mouse malignant melanoma cell line (B16). An expression vector harboring the 65 kDa antigen gene was transfected into B16 using Lipofectamine, then expression of the antigen was confirmed by RT-PCR and Western blotting. Several cell lines expressing 65 kDa antigen were established (B16/65 kDa). We also established a control cell line transfected with the vector alone (B16/con). All cell lines (B16, B16/con, B16/65 kDa) were injected intraperitoneally into syngeneic mice with or without BCG prior immunization and the development of tumor ascites was examined. To analyze the mechanism of the anti-tumor effect, CD4 T cells or CD8 T cells were depleted in vivo by administering the corresponding monoclonal antibody. B16/65k Da expressed the 65 kDa hsp of M. tuberculosis. The tumor growth of B16/65 kDa was slightly retarded in naive mice, but significantly inhibited by BCG. The anti-tumor effect was totally abrogated in mice deficient in CD4 T cells, suggesting that CD4 T cells are involved in this process. The 65 kDa hsp of M. tuberculosis was expressed after gene transduction in a malignant melanoma cell line and significantly enhanced the anti-tumor effect of BCG immunotherapy. CD4 T cells play an important role in this anti-tumor effect. 相似文献