Search results for "MYCOBACTERIUM TUBERCULOSIS"
showing 10 items of 159 documents
Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infe…
2008
D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6(-/-) mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor alpha, int…
Towards next generation diagnostics for tuberculosis: identification of novel molecular targets by large-scale comparative genomics
2019
AbstractTuberculosis remains one of the main causes of death worldwide. The long and cumbersome process of culturingMycobacterium tuberculosiscomplex (MTBC) bacteria has encouraged the development of specific molecular tools for detecting the pathogen. Most of these tools aim to become novel tuberculosis diagnostics, and big efforts and resources are invested in their development, looking for the endorsement of the main public health agencies. Surprisingly, no study had been conducted where the vast amount of genomic data available is used to identify the best MTBC diagnostic markers. In this work, we use large-scale comparative genomics to provide a catalog of 30 characterized loci that ar…
Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells
2018
HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector TÂ cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+TÂ cells in the circulation of patients with active tubercu…
Fast and low-cost decentralized surveillance of transmission of tuberculosis based on strain-specific PCRs tailored from whole genome sequencing data…
2015
Molecular epidemiology has transformed our knowledge of how tuberculosis (TB) is transmitted. Whole genome sequencing (WGS) has reached unprecedented levels of accuracy. However, it has increased technical requirements and costs, and analysis of data delays results. Our objective was to find a way to reconcile speed and ease of implementation with the high resolution of WGS. The targeted regional allele-specific oligonucleotide PCR (TRAP) assay presented here is based on allele-specific PCR targeting strain-specific single nucleotide polymorphisms, identified from WGS, and makes it possible to track actively transmitted Mycobacterium tuberculosis strains. A TRAP assay was optimized to track…
Sequence diversity in the pe_pgrs genes of Mycobacterium tuberculosis is independent of human T cell recognition.
2014
ABSTRACT The Mycobacterium tuberculosis genome includes the large family of pe_pgrs genes, whose functions are unknown. Because of precedents in other pathogens in which gene families showing high sequence variation are involved in antigenic variation, a similar role has been proposed for the pe_pgrs genes. However, the impact of immune selection on pe_pgrs genes has not been examined. Here, we sequenced 27 pe_pgrs genes in 94 clinical strains from five phylogenetic lineages of the M. tuberculosis complex (MTBC). We found that pe_pgrs genes were overall more diverse than the remainder of the MTBC genome, but individual members of the family varied widely in their nucleotide diversity and in…
Characterisation of rpsL, rrs and embB mutations associated with streptomycin and ethambutol resistance in Mycobacterium tuberculosis.
2003
In order to characterise molecular mechanisms of first-line drug resistance in Mycobacterium tuberculosis and to evaluate the use of molecular markers of resistance (gene point mutations), we analysed 66 multi-drug-resistant (MDR) isolates from Latvian tuberculosis patients. They were all resistant to rifampin (RIF), isoniazid (INH) and streptomycin (SM), and 33 were resistant to ethambutol (EMB). Enzymatic digestion by MboII and nucleotide sequencing of the rpsL gene fragment detected a single nucleotide substitution K43R in 40 (61%) of the 66 SM-resistant M. tuberculosis isolates. Of the other 26 SM-resistant isolates, 16 (24%) had mutations at positions 513A--C and 516C--T of the rrs gen…
Whole genome sequencing analysis of intrapatient microevolution in Mycobacterium tuberculosis: potential impact on the inference of tuberculosis tran…
2013
Background. It has been accepted that the infection by Mycobacterium tuberculosis (M. tuberculosis) can be more heterogeneous than considered. The emergence of clonal variants caused by microevolution events leading to population heterogeneity is a phenomenon largely unexplored. Until now, we could only superficially analyze this phenomenon by standard fingerprinting (RFLP and VNTR).Methods. In this study we applied whole genome sequencing for a more in-depth analysis of the scale of microevolution both at the intrapatient and interpatient scenarios.Results. We found that the amount of variation accumulated within a patient can be as high as that observed between patients along a chain of t…
Genomic determinants of speciation and spread of the Mycobacterium tuberculosis complex
2019
14 páginas, 6 figuras
The zebrafish embryo as an in vivo model for screening nanoparticle-formulated lipophilic anti-tuberculosis compounds.
2021
ABSTRACT With the increasing emergence of drug-resistant Mycobacterium tuberculosis strains, new and effective antibiotics against tuberculosis (TB) are urgently needed. However, the high frequency of poorly water-soluble compounds among hits in high-throughput drug screening campaigns is a major obstacle in drug discovery. Moreover, in vivo testing using conventional animal TB models, such as mice, is time consuming and costly, and represents a major bottleneck in lead compound discovery and development. Here, we report the use of the zebrafish embryo TB model for evaluating the in vivo toxicity and efficacy of five poorly water-soluble nitronaphthofuran derivatives, which were recently id…
Nanocarriers for respiratory diseases treatment: Recent advances and current challenges
2014
Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to…