A5040392483- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immunodeficiency and Autoimmune Disorders
- Immune responses and vaccinations
- Diagnosis and treatment of tuberculosis
- Bacteriophages and microbial interactions
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Antibiotic Resistance in Bacteria
- Pneumocystis jirovecii pneumonia detection and treatment
- X-ray Diffraction in Crystallography
- Salmonella and Campylobacter epidemiology
- Crystallization and Solubility Studies
- Pneumonia and Respiratory Infections
- Infectious Diseases and Tuberculosis
- Infectious Diseases and Mycology
- Microfluidic and Bio-sensing Technologies
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- 3D Printing in Biomedical Research
- interferon and immune responses
- Synthesis and biological activity
- Microbial Community Ecology and Physiology
- Health Systems, Economic Evaluations, Quality of Life
- Immune cells in cancer
Instituto de Salud Carlos III
2016-2025
Universidad de Zaragoza
2016-2025
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
2015-2024
Instituto de Investigación Sanitaria Aragón
2014-2024
Instituto de Biocomputación y Física de Sistemas Complejos
2015-2023
Centro Nacional de Microbiologia
2023
Hospital Universitario Miguel Servet
2011-2019
Centro Nacional de Biotecnología
2012-2013
Consejo Superior de Investigaciones Científicas
2012-2013
Instituto Aragonés de Ciencias de la Salud
2011
Significance In 1901, when Robert Koch proposed that the bacilli causing human and bovine tuberculosis were not identical, this view caused much controversy. Now, 113 y later, we know agent, Mycobacterium bovis , together with other animal strains, forms a separate phylogenetic lineage apart from lineages, but molecular reasons why strains only play minor roles in epidemiology remain unknown. Herein, show by genetic transfer virulence experiments specific mutations regulator contribute to...
Inactivation of the transcriptional regulator PhoP results in Mycobacterium tuberculosis attenuation. Preclinical testing has shown that attenuated M. phoP mutants hold promise as safe and effective live vaccine candidates. We focused this study to decipher virulence networks regulated by PhoP. A combined transcriptomic proteomic analysis revealed controls a variety functions including: hypoxia response through DosR crosstalking, respiratory metabolism, secretion major T-cell antigen ESAT-6,...
Two-component regulatory signal transduction systems are important elements of the adaptative response prokaryotes to a variety environmental stimuli. Disruption PhoP-PhoR in Mycobacterium tuberculosis dramatically attenuates virulence, implying that this system directly and/or indirectly coordinates expression virulence factors whose identity remains be established. Interestingly, knockingout two-component M. Mt103, dramatic changes colonial morphology, cording properties, and reactivity...
The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis over 11,000 Mycobacterium tuberculosis mutants. This very stringent makes use fluorescent staining for intracellular acidic compartments, and automated confocal microscopy...
The PhoPR two-component system is essential for virulence in Mycobacterium tuberculosis where it controls expression of approximately 2% the genes, including those ESX-1 secretion apparatus, a major determinant. Mutations phoP lead to compromised production pathogen-specific cell wall components and attenuation both ex vivo vivo. Using antibodies against native protein ChIP-seq experiments (chromatin immunoprecipitation followed by high-throughput sequencing) we demonstrated that PhoP binds...
Abstract MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens ESAT6 and CFP10. These are absent from current BCG. Here we compare protection induced by BCG in several mouse strains naturally express different MHC haplotypes differentially recognizing induces improved C3H mice, only of three tested reactive to both Deletion reduces its efficacy levels, supporting link between greater CFP10- ESAT6-specific...
Abstract Human and animal tuberculosis is caused by the Mycobacterium Complex (MTBC), which has evolved a genomic decay of cobalamin (vitamin B12) biosynthetic genes. Accordingly, in sharp contrast to environmental, opportunistic ancestor mycobacteria; we demonstrate that M. ( Mtb ), africanum , animal-adapted lineages, lack endogenous production cobalamin, yet they retain capacity for exogenous uptake. A B12 anemic model immunocompromised immunocompetent mice, demonstrates improved...
The ESX-1 secreted virulence factor ESAT-6 is one of the major and most well-studied factors Mycobacterium tuberculosis, given that its inactivation severely attenuates virulent mycobacteria. In this work, we show clinical isolates M. tuberculosis produce secrete larger amounts than widely used H37Rv laboratory strain. A search for genetic polymorphisms underlying observation showed whiB6 (rv3862c), a gene upstream locus has not previously been found to be implicated in regulation secretory...
The insertion Sequence IS6110, only present in the pathogens of Mycobacterium tuberculosis Complex (MTBC), has been gold-standard epidemiological marker for TB more than 25 years, but biological implications IS6110 transposition during MTBC adaptation to humans remain elusive. By studying 2,236 clinical isolates typed by IS6110-RFLP and covering MTBC, we remarked a lineage-specific content being higher modern globally distributed strains. Once observed distribution selected representative...
In addition to antibiotics, vaccination is considered among the most efficacious methods in control and potential eradication of infectious diseases. New safe effective vaccines against tuberculosis (TB) could be a very important tool are called play significant role fight TB resistant antimicrobials. Despite extended use current vaccine Bacillus Calmette-Guérin (BCG), continues transmitted actively one 10 causes death world. last 20 years, different have entered clinical trials. this paper,...
At its 100th birthday of first administration to a newborn, BCG has been (and continues being) an inspiration for the construction and development hundreds new TB vaccine candidates in last two half decades. Today, 14 are clinical inside global pipeline. MTBVAC is one these candidates. Based on live-attenuated Mycobacterium tuberculosis isolate, MTBVAC's 25 years discovery, characterisation have followed Pasteur principles, process, served as reference gold standard establishing safety...
Similarities between Mycobacterium tuberculosis phoP-phoR mutants and the attenuated laboratory strain M. H37Ra in terms of morphological cytochemical properties, lipid content, gene expression virulence attenuation prompted us to analyze functionality this two-component regulator latter strain. Sequence analysis revealed a base substitution resulting one-amino-acid change likely DNA-binding region PhoP relative H37Rv. Using gel-shift assays, we show that mutation abrogates ability protein...
Small non-coding regulatory RNAs (sRNAs) have been studied in many bacterial pathogens during infection. However, few studies focused on how intracellular modulate sRNA expression inside eukaryotic cells. Here, we monitored of all known sRNAs Salmonella enterica serovar Typhimurium (S. Typhimurium) bacteria located fibroblasts, a host cell type which this pathogen restrains growth. sequences S. and Escherichia coli were searched the genome virulent strain SL1344, subject study. Expression 84...
BackgroundHuman tuberculosis (TB) is caused by a plethora of Mycobacterium complex (MTBC) strains belonging to seven phylogenetic branches. Lineages 2, 3 and 4 are considered "modern" branches the MTBC responsible for majority worldwide TB. Since current BCG vaccine confers variable protection against pulmonary TB, new candidates investigated. MTBVAC unique live attenuated based on M. in human clinical trials.MethodsMTBVAC was originally constructed unmarked phoP fadD26 deletions isolate L4....
The attenuated Mycobacterium tuberculosis H37Ra strain is an isogenic counterpart of the virulent paradigm H37Rv. Recently, a link between point mutation in PhoP transcriptional regulator and avirulence was established. Remarkably, previous study demonstrated negative autoregulation phoP gene H37Ra. These findings led us to H37Rv strain. In contrast previously published for H37Ra, our experiments using promoter-lacZ fusion showed that positively autoregulated both compared with deletion...