A5101751948- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Immunodeficiency and Autoimmune Disorders
- Diagnosis and treatment of tuberculosis
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Infectious Diseases and Tuberculosis
- Asthma and respiratory diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Bacterial Genetics and Biotechnology
- Inhalation and Respiratory Drug Delivery
- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- RNA and protein synthesis mechanisms
- Neonatal Respiratory Health Research
- Respiratory viral infections research
- Influenza Virus Research Studies
- Cystic Fibrosis Research Advances
- Bladder and Urothelial Cancer Treatments
- Respiratory and Cough-Related Research
- Bacterial Infections and Vaccines
- interferon and immune responses
Universidad de Zaragoza
2016-2025
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
2016-2025
Instituto de Investigación Sanitaria Aragón
2016-2025
Instituto de Salud Carlos III
2016-2025
Hospital Universitari Sant Joan D'Alacant
1996-2025
University of Concepción
2025
Home and Community Care Support Services
2024
Mayo Clinic
2024
WinnMed
2024
Guelph General Hospital
2024
DNA fingerprinting of Mycobacterium tuberculosis has been shown to be a powerful epidemiologic tool. We propose standardized technique which exploits variability in both the number and genomic position IS6110 generate strain-specific patterns. General use this will permit comparison results between different laboratories. Such comparisons facilitate investigations into international transmission may identify specific strains with unique properties such as high infectivity, virulence, or drug...
Abstract Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping widely used PCR-based reverse-hybridization blotting technique that assays genetic diversity this and useful both for clinical laboratory, molecular epidemiology, evolutionary population genetics. It easy, robust, cheap, produces highly diverse portable numerical results, as result...
ABSTRACT In this study, the currently known typing methods for Mycobacterium tuberculosis isolates were evaluated with regard to reproducibility, discrimination, and specificity. Therefore, 90 M. complex strains, originating from 38 countries, tested in five restriction fragment length polymorphism (RFLP) seven PCR-based assays. all methods, one or more repetitive DNA elements targeted. The strain fingerprint analysis performed laboratory most experienced respective method. To examine...
Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two the most widely used attenuated history research are Mycobacterium bovis BCG (BCG) H37Ra (H37Ra), which both during vitro serial passage. Whereas attenuation due mainly loss ESAT-6 secretion system, ESX-1, reason why remained unknown. However, here we show point mutation (S219L) predicted DNA...
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...
Two‐component regulatory proteins function in bacteria as sensory and adaptive factors response to a wide range of environmental stimuli. Some two‐component systems, such PhoP/PhoQ, control transcription key virulence genes essential for survival host cells diverse intracellular bacterial pathogens, including Salmonella sp., Shigella sp. Yersinia In this study, we have disrupted the phoP gene from Mycobacterium tuberculosis , which codes putative regulator factor system PhoP/PhoR. The mutant...
Abstract Alterations in genes involved the repair of DNA mutations (mut genes) result an increased mutation frequency and better adaptability bacterium to stressful conditions. W-Beijing genotype strains displayed unique missense alterations three putative mut genes, including two mutT type (Rv3908 mutT2) ogt. These polymorphisms were found be characteristic phylogenetic lineage. Analysis 55 representative isolates suggests a sequential acquisition mutations, elucidating plausible pathway...
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...
Background Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better regimes. Relevant models are required to downselect most promising vaccines entering clinical testing identify correlates protection. Methods Findings Here, we evaluated immunogenicity protection against in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen...
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...
Precision-cut lung slices (PCLS) allow comparison of the airway responses different species under identical experimental conditions. The aim this study was to establish and characterise PCLS from guinea pigs (GPs) compare them with human PCLS. GP were prepared according previously published procedures exception that agarose solution initial incubation medium contained isoproterenol avoid post mortem contraction. median effective concentrations (EC50, expressed as nM) for agonist-induced...
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...
Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of infection. Nevertheless, role apoptosis during infection with Mycobacterium tuberculosis, causative agent human subject an intense debate and still remains unclear. In this work, we describe that induction in host cells clearly restricted virulent M. tuberculosis strains, associated capacity mycobacteria secrete 6 kDa early secreted antigenic target ESAT-6 bothunder vitro vivo conditions....
Klebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that might be able to persist intracellularly within a vacuolar compartment. This study was designed investigate the interaction between macrophages. Engulfment K. dependent on host cytoskeleton, cell plasma membrane lipid rafts activation phosphoinositide 3-kinase (PI3K). Microscopy studies revealed resides compartment, Klebsiella-containing vacuole (KCV), which traffics vacuoles...
Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking natural route infection. In this work, we have compared pulmonary and subcutaneous delivery BCG in tuberculosis-susceptible DBA/2 mouse strain, a model which parenterally administered does not protect against tuberculosis. Our data show that intranasally but subcutaneously confers robust protection challenge. addition, our results indicate vaccination...
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...
Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects Bacillus Calmette-Guerin (BCG), current vaccine against tuberculosis, have been related not only to specific induction T-cell immunity, but also with long-term epigenetic metabolic reprogramming cells from innate immune system through process termed trained immunity. Here we show that MTBVAC, live attenuated strain...
BCG vaccination can strengthen protection against pathogens through the induction of epigenetic and metabolic reprogramming innate immune cells, a process called trained immunity. We others recently demonstrated that mucosal or intravenous better protects rhesus macaques from Mycobacterium tuberculosis infection TB disease than standard intradermal vaccination, correlating with local adaptive signatures. In line prior mouse data, here, we show in enhances cytokine production associated...