Ontology highlight
ABSTRACT:
PROVIDER: PRJNA633380 | ENA |
REPOSITORIES: ENA
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Project description:Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role.
2022-10-23 | GSE203037 | GEO
Project description:Aging has a significant impact on the immune system, leading to a gradual decline in immune function and changes in the body's ability to respond to bacterial infections. Non-tuberculous mycobacteria (NTM), also known as atypical mycobacteria or environmental mycobacteria, are commonly found in soil, water, and various environmental sources. While many NTM species are considered opportunistic pathogens, some can cause significant infections, particularly in individuals with compromised immune systems, such as the elderly. When mycobacteria enter the body, macrophages are among the first immune cells to encounter them, and attempt to engulf mycobacteria through a process called phagocytosis. Some NTM species, including Mycobacterium avium (M.avium) can survive and replicate within macrophages. However, little is known about the interaction between NTM and macrophages in the elderly. In this study, we investigated the mouse bone marrow-derived macrophage (BMMs) response to M. avium serotype 4, one of the main NTM species in patients with pulmonary NTM diseases. Our results demonstrated that old mouse BMMs have an increased level of intracellular iron and are more susceptible to M. avium serotype 4 infection compared to young mouse BMMs. The whole-cell proteomic analysis indicated a dysregulated expression of iron homeostasis-associated proteins in old mouse BMMs regardless of mycobacterial infection. Deferoxamine, an iron chelator, significantly rescued mycobacterial killing and phagolysosome maturation in old mouse BMMs. Therefore, our data indicate that an intracellular iron overload improves NTM survival within macrophages, and suggest a potential application of iron chelating drugs as a host-directed therapy for pulmonary NTM infection in the elderly
2024-05-24 | PXD045821 | Pride
Project description:Sequence and Analysis of Non-tuberculous Mycobacteria (NTM) strains
| PRJNA305922 | ENA
Project description:Background: Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Currently, there is no method to predict whether patients with cystic fibrosis will develop disease related to non-tuberculous mycobacteria. In non cystic fibrosis populations, several genetic susceptibility factors have been described. In this study, we examined whether patients with cystic fibrosis demonstrate a similar pattern of genetic susceptibility and explored host immune-related biomarkers predictive of NTM pulmonary disease (NTM-PD). Methods: We evaluated whole blood gene expression using bulk RNA-seq in a cohort of CF patients at the time of first isolation of NTM. Differential gene expression was compared in patients who did (n = 12) vs. did not (n= 30) develop NTM-PD following first NTM growth. Results: No differences in demographics or composition of white blood cell sample populations at the time of sample collection were identified between groups. There were no significant differences in the expression of genes previously reported to confer susceptibility to NTM-PD in non-CF populations. However, CF patients who went on to develop NTM-PD had higher expression of genes involved in the interferon ( and ), tumor necrosis factor, and IL6 STAT3 JAK pathways. Conclusion: Patients with CF who develop NTM-PD have increased expression of genes involved in innate immunity, in contrast to non-CF populations where these responses seem to be suppressed.
2022-12-14 | GSE205161 | GEO
Project description:Tuberculosis (TB) is still a major global health challenge, killing over 1.5 million people each year, and hence, there is a need to identify and develop novel treatments for Mycobacterium tuberculosis (M. tuberculosis). The prevalence of infections caused by nontuberculous mycobacteria (NTM) is also increasing and has overtaken TB cases in the United States and much of the developed world. Mycobacterium abscessus (M. abscessus) is one of the most frequently encountered NTM and is difficult to treat. We describe the use of drug-disease association using a semantic knowledge graph approach combined with machine learning models that has enabled the identification of several molecules for testing anti-mycobacterial activity. We established that niclosamide (M. tuberculosis IC90 2.95 μM; M. abscessus IC90 59.1 μM) and tribromsalan (M. tuberculosis IC90 76.92 μM; M. abscessus IC90 147.4 μM) inhibit M. tuberculosis and M. abscessus in vitro. To investigate the mode of action, we determined the transcriptional response of M. tuberculosis and M. abscessus to both compounds in axenic log phase, demonstrating a broad effect on gene expression that differed from known M. tuberculosis inhibitors. Both compounds elicited transcriptional responses indicative of respiratory pathway stress and the dysregulation of fatty acid metabolism. Further testing against drug-resistant isolates and other NTM is warranted to clarify the usefulness of these repurposed drugs for mycobacteria.
2024-03-01 | E-MTAB-13761 | biostudies-arrayexpress