Search results for "TUBERCULOSIS"

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…

Splenic tuberculosis in a patient with Crohn's disease on infliximab: Case report

2010

Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+T cells

2018

HLA-E presented antigens are interesting targets for vaccination given HLA-Es’ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector T 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+T 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

Caracterización epidemiológica, clínica, microbiológica y genómica de Mycobacterium tuberculosis en el Departamento de Salud La Fe de Valencia

2017

Tesis doctoral, 152 págs

Intestinal tuberculosis as a cause of chronic diarrhoea among patients with human immunodeficiency virus infection: report of two cases.

2001

In Western countries human immunodeficiency virus infection is considered the main risk factor of tuberculous disease, its incidence being 500 times higher in HIV-infected patients than in the general population. Despite the disease frequently present in these patients with extraintestinal manifestations, intestinal localization is rarely observed and often as a consequence of complications such as acute gastrointestinal bleeding or perforation. The diagnosis of intestinal tuberculosis is difficult and is often delayed due to the lack of specific signs and symptoms as well as the low sensitivity of routine methods. A review of the literature is made and personal experience in the diagnosis …