Centro Colombiano Of Investigacion En Tuberculosis

Medellín, Colombia

Centro Colombiano Of Investigacion En Tuberculosis

Medellín, Colombia

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Realpe T.,Corporacion para Investigaciones Biologicas | Realpe T.,Pontifical Bolivarian University | Realpe T.,Centro Colombiano Of Investigacion En Tuberculosis | Correa N.,Corporacion para Investigaciones Biologicas | And 29 more authors.
PLoS ONE | Year: 2014

Background: Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. Principal Findings: A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). Conclusions: This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage. © 2014 Realpe et al.


Sanchez D.,Institute Investigaciones Medicas | Sanchez D.,Centro Colombiano Of Investigacion En Tuberculosis | Sanchez D.,Louisiana State University | Lefebvre C.,Montreal Heart Institute | And 6 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

BACKGROUND: The molecular basis of genetic predisposition to pulmonary tuberculosis (PTB) in adults remains largely elusive. A chronic granulomatous inflammatory reaction is one of the main characteristics of the immune response to TB; however, a similar reaction is observed in other diseases, such as Crohn's disease. OBJECTIVE: To assess the association of genetic polymorphisms previously associated with Crohn's disease and PTB in a Colombian population of PTB patients and controls. DESIGN: A case-control study was performed among 500 newly diagnosed PTB patients and 320 healthy control subjects. Thirty-one single nucleotide polymorphisms (SNPs) identified in a previous meta-analysis of genome-wide association studies of Crohn's disease were used for genotyping using MassARRAY technology. RESULTS: In this study, we identified an association with borderline significance (P = 0.0009433 and P = 0.029 after multiple testing by Bonferroni's correction) of SNP rs10995271 with PTB. SNP rs10995271 is in linkage disequilibrium with SNPs belonging to the zinc finger protein (ZNF365) gene. CONCLUSIONS: Our results suggest that human PTB shares a genetic basis with Crohn's disease, and that SNPs in the ZNF365 gene would have a role in the occurrence of chronic granulomatous inflammatory reaction in TB as well as Crohn's disease. ©2014 The Union.


Cubillos-Ruiz A.,Corporacion Corpogen | Sandoval A.,Corporacion Corpogen | Ritacco V.,Instituto Nacional Of Enfermedades Infecciosas Anlis Carlos G Malbran | Lopez B.,Instituto Nacional Of Enfermedades Infecciosas Anlis Carlos G Malbran | And 8 more authors.
Journal of Clinical Microbiology | Year: 2010

Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Castano D.,University of Antioquia | Castano D.,Centro Colombiano Of Investigacion En Tuberculosis | Garcia L.F.,University of Antioquia | Garcia L.F.,Centro Colombiano Of Investigacion En Tuberculosis | And 2 more authors.
Tuberculosis | Year: 2011

Monocytes from tuberculosis patients exhibit functional and phenotypical alterations compared with healthy controls. To determine whether these discrepancies can be explained by changes in monocyte subsets, the expression of CD14 and CD16 was evaluated in tuberculosis patients and healthy controls; additionally, some markers related to the mononuclear phagocytes maturation, differentiation and function, such as CD1a, CD1c, CD11b, CD11c, CD13, CD33, CD36, CD40, CD64, CD68, CD80, CD83, CD86, HLA-DR, CCR2, CCR5, and non-specific esterases (NSE) were determined in monocyte subsets. Patients had increased percentage of circulating CD14 HiCD16 + and CD14 LoCD16 + monocytes. The percentage of monocytes expressing CD11b, CD36, CD64, CD68, CD80, CD86, CCR2 and NSE was lower in CD14 HiCD16 + and CD14 LoCD16 + cells than in CD14 HiCD16 - monocytes. M. tuberculosis infected CD16 + monocytes produced more TNF-α and less IL-10 than CD16 - cells at 6 h post-infection. Isolated CD16 + monocytes spontaneously underwent apoptosis during differentiation into macrophages; in contrast to CD16 - monocytes that became differentiated into monocyte-derived macrophages (MDM) with a minimal induction of cell death. In addition, there were more Annexin V and propidium iodide positive monocytes in the CD16 + subset infected with live M. tuberculosis at 24 h than CD16 - monocytes. Under the culture conditions established for this study, the monocyte subsets did not differentiate into dendritic cells. These results show that tuberculosis patients have an augmented frequency of CD16 + circulating monocytes which are more prone to produce TNF-α and to undergo cell death in response to M. tuberculosis infection. © 2011 Elsevier Ltd. All rights reserved.


Castano D.,University of Antioquia | Castano D.,Centro Colombiano Of Investigacion En Tuberculosis | Garcia L.F.,University of Antioquia | Garcia L.F.,Centro Colombiano Of Investigacion En Tuberculosis | And 2 more authors.
Tuberculosis | Year: 2014

The heterogeneity of mononuclear phagocytes, partially explained by cell differentiation, influences the activation of innate responses. It has been reported that Mycobacterium tuberculosis inhibits monocyte differentiation into either dendritic cells or macrophages. To evaluate whether the activation of effector mechanisms against M. tuberculosis differ between less and more differentiated mononuclear phagocytes, we compared monocytes differentiated in vitro for 24 h (MON24) and 120 h (MDM120) infected with M. tuberculosis H37Rv, H37Ra and the clinical isolate UT127 at different multiplicity of infection. MDM120 phagocytosed more M. tuberculosis, inhibited mycobacterial growth and did not die in response to the infection, compared with MON24. In contrast, MON24 become Annexin V and Propidium iodide positive after 36 h of M. tuberculosis infection. Although, there were striking differences between MON24 and MDM120, there were also some differences in the response to the mycobacterial strains used. Finally, in MDM120 infected with M. tuberculosis H37Rv, a lower percentage of mycobacterial phagosomes accumulated transferrin and a higher percentage co-localized with cathelicidin than in MON24. These results demonstrate that innate responses induced by M. tuberculosis depends upon the stage of differentiation of mononuclear phagocytes and support that terminally differentiated cells are more efficient anti-mycobacterial effectors than the less differentiated ones. © 2014 Elsevier Ltd. All rights reserved.


Cobat A.,McGill University | Orlova M.,McGill University | Barrera L.F.,University of Antioquia | Barrera L.F.,Centro Colombiano Of Investigacion En Tuberculosis | And 2 more authors.
Public Health Genomics | Year: 2013

Tuberculosis (TB), caused by the human pathogenic bacterium Mycobacterium tuberculosis, poses a major global health problem. The tubercle bacillus is transmitted from person to person by aerosol, but only a proportion of those in contact with infectious aerosol particles will become infected. If infection occurs, less than 10% of those infected will develop clinical signs of TB, while the majority will develop latent TB infection (LTBI). The identification and treatment of LTBI persons is a major aspect of TB control, especially in low-incidence, highly developed nations. In the absence of a gold standard test for latent TB, infection is inferred with the help of either the in vivo tuberculin skin test or in vitro interferon gamma release assays of anti-mycobacterial immunity. Recent work has observed high heritability of these immune assays indicating the critical role of the host genetic background on the establishment of infection and latency. Additional genetic studies have identified the host genetic background as an important covariate for the proper interpretation of the results obtained from LTBI assays. Taken together, these data suggest TB surveillance and control can likely be improved by including host genetic information into the interpretation of these widely used assays. Copyright © 2013 S. Karger AG, Basel.

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