Project description:Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all cause post-infectious morbidity and mortality. We show that TCA cycle also regulates epigenetics, specifically DNA methylation, after infection induced immune tolerance. This data from TB patients who received everolimus with standard of care antibiotics, and have less DNA hypermethylation demonstrating proof of concept that metabolic manipulation can mitigate epigenetic scars.
Project description:Tuberculosis (TB) is one of the top ten causes of death worldwide and the leading cause of death from a single infectious agent. Globally, an estimated of 10 million people developed TB in 2018 according to WHO report. An estimated one third of all TB cases are not diagnosed or notified, partly due to the major limitations of current diagnostic tools. To achieve the goals of the WHO’s End TB Strategy, which targets for 2030 a 90% reduction in the number of TB deaths and an 80% reduction in the TB incidence rate compared with levels in 2015, diagnostic tools are critically important. Among the three diagnostic priorities identified by the WHO and the TB community is the development of a point-of-care biomarker-based non-sputum-based test to diagnose pulmonary TB, and ideally also extrapulmonary TB. To be successfully implemented at point-of-cares, a new test should use an easily accessible sample, such as urine, blood or breath condensate. Here, we explored whether bacilli-derived molecules released in the extracellular milieu during infection could be detected in the exhaled breath condensate, allowing a specific diagnosis of TB. Interestingly, we detected by proteomic analysis a set of Mycobacterium tuberculosis proteins in all smear-positive and smear-negative adult patients, as well as of children with TB
Project description:Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) strains and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence data. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB (HR-MTB), 7 were resistant only to one antibiotic (3 were resistant only to ethambutol and 3 isolate to streptomycin while one isolate showed resistance to fluoroquinolones), 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB (pre-XDR). This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of TB infection.
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:We present the data obtained from high-resolution ribosome profiling analysis of Mycobacterium tuberculosis grown under standard conditions (log phase) and cells subjected to oxidative stress (50 µM cumene hydroperoxide) and pH stress (pH 4.5). Our data shows pervasive ribosome pausing in the M. tb translatome. A large number of genes show very high pause immediately downstream to the translation start site. Moreover, serines and alanines in the E site of the ribosome exhibit highest pause scores.