Project description:Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health burden, characterized by complex host–pathogen interactions that drive heterogeneous clinical outcomes. While pulmonary epithelial cells are increasingly recognized as active participants in innate immunity during Mtb infection, how host defences are altered when the epithelial barrier is compromised remains unclear . In this study, we developed a murine model combining naphthalene-induced airway epithelial injury with Mtb infection, and found a pronounced impairment in pulmonary bacterial clearance. Through single-cell RNA sequencing (scRNA-seq), we mapped the pulmonary cells landscape and identified widespread suppression of epithelial immune functions. Notably, we observed macrophages transition from an antimicrobial to an antigen-presenting phenotype, indicating waning pulmonary innate defenses and heightened adaptive immune activation. These findings highlight the pivotal role of pulmonary epithelial integrity in shaping host immunity against Mtb and offer new insights into potential therapeutic strategies targeting barrier–immune crosstalk.
Project description:Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA of Mtb, using tRNA sequencing (tRNA-seq). Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion of Mtb genes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species.
Project description:We have performed parallel ribosome profiling and RNA sequencing to determine which mRNAs are being translated during exponential growth and following 24 hours of nutrient starvation in the human pathogen Mycobacterium tuberculosis.
Project description:The aim of this study was to extend our analysis to the obligate human pathogen M. tuberculosis, which has to deal with a more restricted set of environmental variables in terms of nitrogen sources, and to delineate the GlnR regulon, by peforming global analysis of GlnR-DNA interactions by Chromatin Immunoprecipitation and high-throughput sequencing (ChIP-seq) over nitrogen run-out.
Project description:We report a pilot investigation for poly-A RNAs differentially expressed during Mycobacterium tuberculosis infection. Participation in this investigation from March 2010 to July 2013 was voluntary, only subjects that were >18 years old and that informed written consent were considered eligible. The recruitment of tuberculosis (TB) patients was done at public hospitals in Rio de Janeiro, Brazil. The diagnostic criteria for active pulmonary tuberculosis was at least one AFB (acid-fast bacilli) -positive sputum sample for M. tuberculosis and/or positive sputum culture and/or compatible clinical evolution for pulmonary TB and less than 15 days of anti-TB treatment and was in accordance with those of the Brazilian Ministry of Health. Blood was collected from recent close contacts (rCt) and active tuberculosis (TB) index cases (n=6). Latent TB infection (LTBI) was accessed by both tuberculin skin test (TST, cut-off = 5mm) and in house interferon-gamma release assays (IGRA, cut-off = 100 pg/ml), therefore, 12 rCt were classified as uninfected controls and 16 with LTBI. Subsequently, the sequencing was performed following the standard protocols on Illumina HiSeq® 2500 Sequencing System (Illumina, San Diego, CA) running 100 bp paired-end reads (PE100) and generating approximately 30 million reads passing filter for each sample to produce the mRNA reads. Mining these RNAseq data, highly prominent modulation of DOCK9, EPHA4, and NPC2 mRNA expression was observed in the TB samples, indicating that they might have a role in TB pathogenesis. These differential modulations upon M. Tuberculosis infection were further validated by additional evidences in larger cohorts from different geographical areas.
Project description:Pulmonary tuberculosis is a multigene disease, and some of the genes affect the development of Pulmonary tuberculosis. The study wants to find different expression genes in blood from Pulmonary tuberculosis patient and normal people who have genetic relationship wtih each other. We used microarrays to detail the global programme of gene expression in the blood between Pulmonary tuberculosis patient's and normal people's who have genetic relationship wtih each other.
Project description:To understand the host-pathogen association by determining the patient SNPs associated with Mycobacterium tuberculosis genotypes in the Ugandan population. by analysing the relationship between the SNPs and different Mtb genotypes, the study seeks to explain why the Mtb Ugandan genotype is prevalent in Uganda and uncover host pathogen related therapies towards that are increasing being discussed as possible adjunct treatments for tuberculosis.
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.