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Bueno J.,Instituto Nacional Of Salud | Bueno J.,Centro Colombiano Of Investigacion En Tuberculosis Ccitb | David Coy E.,National University of Colombia | Stashenko E.,Industrial University of Santander
Revista Espanola de Quimioterapia | Year: 2011

It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug-resistance. For over 50 years, natural products have served us well on combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites have helped to double our life span, reduced pain and suffering, and revolutionized medicine. Colombia is a megadiverse country with enormous potential to offer leads for new antimycobacterial drugs. The principal aim of this article is to show a state of the art on antimycobacterial natural products research in Colombia compared to the rest of the world, in order to develop programs for bioprospecting with a view to determining the biological activity for pharmaceutical and industrial application of natural products in our country. Source

Quiroga J.,University of Valle | Diaz Y.,University of Valle | Bueno J.,Centro Colombiano Of Investigacion En Tuberculosis Ccitb | Insuasty B.,University of Valle | And 4 more authors.
European Journal of Medicinal Chemistry | Year: 2014

Three series of novel 4-arylbenzo[h]pyrazolo[3,4-b]quinolin-5,6-diones 4, 7 and 9 have been efficiently obtained in good yields by three-component microwave assisted reaction between aminopyrazoles 1 or 6 (both 1-phenyl and 1-H substituted), 2-hydroxynaphthoquinone 2 and benzaldehydes 3. Compounds 4, 7 and 9 have been evaluated against fifteen Mycobacterium spp strains, and six of them have shown antimycobacterial activity. The highest inhibitory activity with MIC ≤2 μg/mL for three of these compounds (4a, 4b and 4g) was related with their highest lipophilicity and lesser polarity within these series. © 2014 Elsevier Masson SAS. All rights reserved. Source

Reyes A.,University of Washington | Sandoval A.,Molecular Genetics | Cubillos-Ruiz A.,Molecular Genetics | Varley K.E.,University of Washington | And 14 more authors.
BMC Genomics | Year: 2012

Background: The insertion element IS6110 is one of the main sources of genomic variability in Mycobacterium tuberculosis, the etiological agent of human tuberculosis. Although IS 6110 has been used extensively as an epidemiological marker, the identification of the precise chromosomal insertion sites has been limited by technical challenges. Here, we present IS-seq, a novel method that combines high-throughput sequencing using Illumina technology with efficient combinatorial sample multiplexing to simultaneously probe 519 clinical isolates, identifying almost all the flanking regions of the element in a single experiment.Results: We identified a total of 6,976 IS6110 flanking regions on the different isolates. When validated using reference strains, the method had 100% specificity and 98% positive predictive value. The insertions mapped to both coding and non-coding regions, and in some cases interrupted genes thought to be essential for virulence or in vitro growth. Strains were classified into families using insertion sites, and high agreement with previous studies was observed.Conclusions: This high-throughput IS-seq method, which can also be used to map insertions in other organisms, extends previous surveys of in vivo interrupted loci and provides a baseline for probing the consequences of disruptions in M. tuberculosis strains. © 1900 Reyes et al.; licensee BioMed Central Ltd. Source

Sanchez D.,University of Antioquia | Sanchez D.,Centro Colombiano Of Investigacion En Tuberculosis Ccitb | Lefebvre C.,Montreal Heart Institute | Lefebvre C.,University of Notre Dame | And 5 more authors.
International Journal of Immunogenetics | Year: 2012

Immunological studies have supported the idea that innate immunity is critical for the control of Mycobacterium tuberculosis (Mtb) infection in humans. Despite the overwhelming evidence showing the critical role of Toll-like receptors (TLRs) in the in vitro recognition of Mtb, the in vivo significance of individual TLRs has been more difficult to demonstrate consistently. We were interested in examining the role of genes of TLRs and molecules involved in their signalling cascades, and a case-control study was designed to test the association of polymorphisms of these innate immune genes with pulmonary tuberculosis (TB) in a Colombian population. In this study, we did not find an association with TLR2, TLR4, TLR9, MyD88 or MAL/TIRAP polymorphic variants. These findings suggest that those genes are not involved as risk factors for pulmonary TB in our population. © 2012 Blackwell Publishing Ltd. Source

Rueda C.M.,University of Antioquia | Marin N.D.,University of Antioquia | Garcia L.F.,University of Antioquia | Garcia L.F.,Centro Colombiano Of Investigacion En Tuberculosis Ccitb | And 2 more authors.
Tuberculosis | Year: 2010

Patients with pulmonary tuberculosis (PTB) frequently have reduced IFN-γ production in response to mycobacterial antigens, compared to individuals with latent Mycobacterium tuberculosis infection (LTBi). However, it is not clear whether this reduced responsiveness is restricted to a particular T cell subset. Herein, PBMCs from 26 PTB patients, 30 household contacts (HHCs) of PTB, and 30 tuberculin positive (TST+) healthy subjects not recently exposed to PTB, were stained with CFSE and stimulated non-specific (PPD) for 120 h, and specific (CFP-10/ESAT-6) and latency (HSpX) mycobacterial antigens for 144 h and the percentage of CD4 + and CD8 +IFN-γ + T cells responding determined by flow cytometry, in addition to their memory phenotype by the CD45RO and CD27 expression. PTB had decreased frequency of both CD4 + and CD8 + precursor cells, as well as decreased number of CD4 +IFN-γ + cells in response to all antigens, whereas CD8 +IFN-γ + cells were decreased in response to PPD and ESAT-6, but not to CFP-10 and HSpX. HHCs exhibited the highest precursor frequencies and IFN-γ responses, irrespective of the antigen employed. The CD4 +/CD8 + cell ratios showed that in response to PPD CD4 + precursor and IFN-γ-producer cells are more frequent than their CD8 + counterparts, and that PTB have a decreased CD4 +IFN-γ +/CD8 +IFN- γ + ratio in response to PPD, CFP-10, and ESAT-6. CD4 +IFN-γ + and CD8 +IFN-γ + cells exhibited a central memory phenotype (CD45RO +CD27 +), irrespective of the group of subjects and the antigen used for stimulation. In conclusion, PTB patients had a decreased percentage of CD4 + and CD8 + precursor cells and CD4 +IFN-γ +. HHCs exhibited the highest frequency of CD4 + and CD8 + precursors and CD4 +IFN-γ +-producing cells. © 2010 Elsevier Ltd. All rights reserved. Source

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