Tuberculosis最新文献

{"title":"The immunomodulatory effects of Mesenchymal stem cells on THP-1-derived macrophages against Mycobacterium tuberculosis H37Ra infection.","authors":"Qianwei Yang, Yiqun Zhou, Waqas Farooq, Qimiao Liu, Jinhui Duan, Li Xing, Changxin Wu, Li Dong","doi":"10.1016/j.tube.2024.102593","DOIUrl":"10.1016/j.tube.2024.102593","url":null,"abstract":"<p><strong>Background: </strong>Immune imbalance is crucial in tuberculosis pathogenesis and may be modulated by mesenchymal stem cells (MSCs). However, how MSCs regulate the host's response to Mycobacterium tuberculosis (Mtb) is unclear.</p><p><strong>Methods: </strong>Human umbilical cord-derived MSCs were co-cultured with Mtb-infected THP-1 macrophages. The intracellular release of ROS in macrophages was measured by DCFH-DA. Cytokine expression was measured by RT-qPCR, apoptosis by Annexin V/PI assay, and pyroptosis markers by Western blotting. Differentially expressed genes (DEGs) in Mtb-infected THP-1 co-cultured with or without MSCs were identified by RNA-seq and potential signaling pathways were analyzed through bioinformatics.</p><p><strong>Results: </strong>The fibroblastic morphology of MSCs exhibited 95 % positivity for CD73, CD90, and CD105, while the positivity rate for negative marker HLA-DR was less than 2 %. In Mtb-infected THP-1 macrophages, co-culturing with MSCs increased ROS release, cytokines expression (IL-1β, IL-6, TNF-α), apoptosis, and pyroptosis markers (NLRP3, Caspase-1, and GSDMD). Comparative transcriptome analysis identified 347 up-regulated and 291 down-regulated DEGs, primarily associated with receptor-ligand interactions and enriched in cytokine signaling pathways including JAK-STAT, TNF, ferroptosis, and autophagy.</p><p><strong>Conclusion: </strong>MSCs could enhance the macrophages' immune response to Mtb by activating immune receptors and inflammatory signaling pathways.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"102593"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Study on the role and molecular mechanism of METTL3-mediated miR-29a-3p in the inflammatory response of spinal tuberculosis\" [Tuberculosis 148 (2024) 102546].","authors":"Xiaojun Ma, Yuxin Gao, Zhibo Ren, Hui Dong, Xu Zhang, Ningkui Niu","doi":"10.1016/j.tube.2024.102590","DOIUrl":"10.1016/j.tube.2024.102590","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":" ","pages":"102590"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of tetracycline analogues with increased aqueous stability for the treatment of mycobacterial infections.","authors":"Jiuyu Liu, Gregory A Phelps, Christine M Dunn, Patricia A Murphy, Laura A Wilt, Victoria Loudon, Robin B Lee, Dinesh Fernando, Lei Yang, Kristina N Tran, Brennen T Troyer, Andres Obregon-Henao, Richard E Lee","doi":"10.1016/j.tube.2024.102592","DOIUrl":"10.1016/j.tube.2024.102592","url":null,"abstract":"<p><p>Tetracycline analogs from the minocycline family have recently shown promise for the treatment of non-tuberculous mycobacterial infections. However, current tetracycline and minocycline therapeutics can be limited by tolerability, stability, or inactivation by TetX. In this study, a series of novel 9-heteroaryl substituted minocycline analogs were designed and synthesized, which resulted in analogs with good in vitro activity against Mycobacterium tuberculosis and Mycobacterium abscessus, stability in water for more than 7 days, avoidance of TetX inactivation in M. abscessus, and a lack of cytotoxicity in HepG2 mammalian cells. In vivo efficacy was confirmed for the tetracycline analogs in an acute model of GM-CSF KO mice infected with M. abscessus, displaying superior efficacy to standard-of-care antibiotic clarithromycin. Molecular modeling and potentiation assays demonstrate avoidance of MabTetX, and the structure-activity relationships of the series are discussed herein for M. tuberculosis and M. abscessus.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"102592"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of pleural fluid-derived extracellular vesicles as a source of Mycobacterium tuberculosis antigens MPT51 and MPT64 for pleural TB diagnosis: a proof-of-concept study.","authors":"Neha Jindal, Pratibha Sharma, Sachin Punia, Manisha Dass, Divya Anthwal, Rakesh Kumar Gupta, Manpreet Bhalla, Ritu Singhal, Ashish Behera, Rakesh Yadav, Sunil Sethi, Sahajal Dhooria, Ashutosh Nath Aggarwal, Sagarika Haldar","doi":"10.1016/j.tube.2024.102578","DOIUrl":"10.1016/j.tube.2024.102578","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have recently emerged as a source of microbe-specific biomarkers for disease diagnosis. In the present study, we evaluated the utility of pleural fluid-derived extracellular vesicles (pEVs) as a source of Mycobacterium tuberculosis (M. tb.) antigens for pleural TB (pTB) diagnosis. EVs were isolated from pleural fluid (PF) samples and were characterized by scanning electron microscopy, and immunoblotting by targeting CD63 and LAMP2 markers. Antigen-detection ELISAs were developed for 2 M.tb.-specific antigens, MPT51 and MPT64 in pEVs (pEV-ELISA) and direct PF samples (PF-ELISA), and were evaluated on n = 86 samples in a blinded manner. Cut-off values were calculated by ROC-curve analysis to achieve 90 % (95%CI:73.47-97.89) and 86.67 % (95%CI:69.28-96.24) specificity for MPT51 and MPT64 pEV-ELISA respectively. The sensitivity of pEV-ELISA was 71.43 % (95%CI; 29.04-96.33) for MPT51 antigen and 57.14 % (95%CI; 18.41-90.1) for MPT64 antigen in the 'Definite' pTB group, while in the 'Definite and Probable' pTB group, the sensitivity was 62.86 % (95%CI:44.92-78.53) for MPT51 and 65.71 % (95%CI:47.79-80.87) for MPT64. The performance of PF-ELISA was sub-optimal, with 28.57 % (95%CI:3.67-70.96) and 14.29 % (95%CI:0.36-57.87) sensitivity for MPT51 and MPT64 in 'Definite' pTB group respectively. We conclude that M. tb.-antigens are concentrated in the EV-fraction of PF samples and EVs can be utilized for antigen-detection assays for pTB diagnosis.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"102578"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A survey of physicians, biomedical researchers and college-educated adults in urban north India about inhaled therapies.","authors":"Khushboo Verma, Amit Misra","doi":"10.1016/j.tube.2024.102591","DOIUrl":"10.1016/j.tube.2024.102591","url":null,"abstract":"<p><p>We surveyed 15 persons with a medical qualification, 133 graduate students doing biomedical research and 56 students or working people with a college education in any discipline. Questions were designed to gauge awareness about inhaled therapies for tuberculosis (TB), non-tubercular mycobacterial lung disease (NTM-LD) and idiopathic pulmonary fibrosis (IPF). Respondents from six cities in North India, aged between 21 and 57 years answered 20 questions. All physicians, 99.25 % of graduate students and 85.71 % of the rest were aware and positive about inhalations for asthma, but these proportions fell to 69.92 and 66.07 in respect of other diseases. All respondents in the first two categories agreed that it was easy to train patients in the use of inhalation devices, while the third group was unanimous that there would be no aversion to using inhalation devices. A question asking whether the respondent would prescribe or opt for inhaled therapies for own use elicited an affirmative answer only from 40.00 % of physicians, 43.61 % of researchers and 23.21 % of college-educated persons (overall: 37.56 %). We concluded that inhaled therapies for diseases other than asthma are not well known and find limited acceptance among the populations sampled.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"102591"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analogue of the natural product ecumicin causes sustained growth inhibition of Mycobacterium tuberculosis under multiple growth conditions.","authors":"Maxwell T Stevens, Paige M E Hawkins, Trixie Wang, Richard J Payne, Warwick J Britton","doi":"10.1016/j.tube.2024.102594","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102594","url":null,"abstract":"<p><p>Multi-drug-resistant Mycobacterium tuberculosis is an escalating global health problem, and a strong pipeline of novel compounds is needed to combat rising antimicrobial resistance. Ecumicin is a novel analogue of the natural antimycobacterial cyclic peptide ecumicin, with selective activity against Mycobacterium species. The activity of ecumicin∗ was compared to that of frontline tuberculosis therapies under in vitro conditions representative of niches where M. tuberculosis resides in the human lung. M. tuberculosis expressing luciferase was cultured in defined 7H9-based media containing glucose, butyrate, valerate, acidified glucose, low or high cholesterol concentrations, or intracellularly in human THP-1 and mouse RAW264.7 macrophages. Ecumicin∗ effectively killed M. tuberculosis under all assay conditions. The IC₉₀ of ecumicin∗ was increased in acidified 7H9 media, and both IC₉₀ and AUC₉₀ values were increased in valerate, cholesterol, high cholesterol culture media. In time-kill assays, anti-M. tuberculosis activity of ecumicin∗ was sustained for 28 days. By comparison, IC₅₀ and IC₉₀ of isoniazid were decreased in butyrate and cholesterols medias, and mycobacterial regrowth occurred in glucose and cholesterol culture medias within 14 days at high isoniazid concentrations. Ecumicin∗ inhibited M. tuberculosis growth in THP-1 macrophages, and at higher IC₉₀ in mouse RAW264.7 macrophages. Drug testing under disease-relevant conditions is important prior to in vivo examination, and ecumicin∗ has proven effective in multiple in vitro conditions typical of the lung environment of tuberculosis patients.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"102594"},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy.","authors":"Petter Holmberg, Martina Janoušková, Tobias Schmidt, Ariane Neumann, Oskar Olsson, Per-Erik Isberg, Maja Reimann, Kristian Riesbeck, Sten Skogmar, Per Björkman","doi":"10.1016/j.tube.2024.102595","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102595","url":null,"abstract":"<p><strong>Background: </strong>Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT).</p><p><strong>Methods: </strong>Individuals with likelihood of recent Mtb exposure, aged 15-25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included. Persons with TBI were sampled prior to TPT (IGRA + pre-treatment, n = 15) or after completion of TPT (IGRA + post-treatment, n = 15). Five persons without TBI were included as controls (IGRA-). Levels of 40 mediators related to TB immune control in blood incubated with Mtb antigens in the QuantiFERON-TB Plus® kit were assessed with electrochemiluminescence assay and compared between participant categories.</p><p><strong>Results: </strong>The concentration of 10 mediators (GM-CSF, interferon-γ, IL-2, I-TAC, IL-12, IP-10, I-309, MCP-2, MIG, and VEGF) significantly differed between IGRA + pre-treatment and IGRA-. A non-significant trend in levels of these markers was observed between IGRA + pre-treatment, IGRA + post-treatment and IGRA-. Based on these mediators two clusters were identified: A (n = 16), including 5 IGRA-, 4 IGRA + pre-treatment, 7 IGRA + post-treatment and B (n = 19), including 11 IGRA + pre-treatment and 8 IGRA + post-treatment.</p><p><strong>Conclusion: </strong>Plasma levels of several Mtb-triggered mediators differed with regard to TBI status among persons recently exposed to TB, suggesting the potential for alternative markers to assess TBI status. Longitudinal analysis of these mediators during TPT is warranted to explore whether these markers can be used to assess likelihood of persistence of viable bacilli in Mtb-exposed individuals.</p><p><strong>Clinicaltrials: </strong>govID:NCT05621343.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"102595"},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of BCG scar among vaccinated children and its correlation with Mantoux skin test at Omdawanban area, Sudan.","authors":"Sabir Awad Mustafa","doi":"10.1016/j.tube.2024.102596","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102596","url":null,"abstract":"<p><strong>Purpose: </strong>Tuberculosis (TB) remains a significant public health concern globally. Bacille Calmette-Guérin (BCG) vaccination is widely used, but scar formation post-vaccination is not universal, which raises concerns about its efficacy. The Mantoux test is used to assess the immune response following BCG vaccination. This study aims to evaluate the prevalence of BCG scar formation among vaccinated children and its correlation with Mantoux test reactions.</p><p><strong>Methods: </strong>This quantitative, cross-sectional descriptive study was conducted among children aged 3 months to 9 years at the vaccination office in Omdawanban, Sudan, from September to October 2021. Data were collected using structured surveys and the Mantoux skin test.</p><p><strong>Results: </strong>Out of 350 vaccinated children, 285 (81.4 %) exhibited a visible BCG scar, while 65 (18.6 %) did not. Mantoux test positivity was observed in 132 children (37.7 %). A significant association was found between the presence of a BCG scar and a positive Mantoux test result (p < 0.05), with 39.3 % of children with a visible scar showing positive Mantoux results compared to 30.8 % of children without a scar. The likelihood of a positive Mantoux test was 3.2 times higher in children with a visible BCG scar (OR = 3.2, 95 % CI [1.8-5.8]). Mantoux positivity also varied by age, with the highest rate (41.2 %) observed among children aged 5-9 years (p = 0.03).</p><p><strong>Conclusions: </strong>There is a significant association between BCG scar formation and Mantoux test positivity. Improved training for healthcare workers and better education for mothers about vaccination are recommended.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"102596"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired control of Mycobacterium tuberculosis infection in mast cell-deficient KitW-sh/W−sh mice","authors":"Berenice Villareal-Rivota ,&nbsp;Yatsiri G. Meneses-Preza ,&nbsp;Marcia Campillo-Navarro ,&nbsp;Bibiana Patricia Ruiz-Sánchez ,&nbsp;Rodolfo Soria-Castro ,&nbsp;Jorge Barrios-Payán ,&nbsp;Dulce Mata-Espinosa ,&nbsp;Luis Donis-Maturano ,&nbsp;Sonia M. Pérez-Tapia ,&nbsp;Alma D. Chávez-Blanco ,&nbsp;Sergio Estrada-Parra ,&nbsp;Rogelio Hernández-Pando ,&nbsp;Rommel Chacón-Salinas","doi":"10.1016/j.tube.2024.102587","DOIUrl":"10.1016/j.tube.2024.102587","url":null,"abstract":"<div><div>Tuberculosis (TB) is a global health problem with diverse clinical manifestations. Different cells of the immune response participate in containing the infection, mainly through the development of granulomas. Mast cells (MCs) are hematopoietic cells that participate in the immune response to different pathogens, and <em>in vitro</em> evidence indicates that they can be activated by <em>Mycobacterium tuberculosis</em> (Mtb). The aim of this study was to evaluate the role of MCs in a murine TB model. We observed that Kit^W-sh/W−sh mast cell-deficient mice showed increased bacterial load in the lungs and the spleen compared to wild-type C57BL/6 mice. Furthermore, MC-deficient mice showed fewer pulmonary granulomas but an early higher inflammatory infiltrate. Interestingly, serum cytokine levels were altered in MC-deficient mice, which showed increased levels of IL-4, IL-5, and IL-22 during the early phase of the infection but increased levels of IFN-γ, IL-9, IL-10, and IL-21 during the late phase of the infection. These results show that mast cells play an important role during Mtb infection by modulating the immune response to the bacteria.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102587"},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of BMVC-8C3O as a novel Pks13 inhibitor with anti-tuberculosis activity","authors":"Tianjun Liu ,&nbsp;Jianzhou Meng ,&nbsp;Bin Wang ,&nbsp;Xiaohui Li ,&nbsp;Qian Wang ,&nbsp;Sihan Liu ,&nbsp;Yan Guan ,&nbsp;Xiao Wang ,&nbsp;Yishuang Liu","doi":"10.1016/j.tube.2024.102579","DOIUrl":"10.1016/j.tube.2024.102579","url":null,"abstract":"<div><div>Given the increasing prevalence of drug-resistant tuberculosis (TB), there is an urgent demand in developing novel anti-TB medications with highly effective, safe, and utilize innovative mechanisms of action. Blocking the mycolic acid synthesis pathway is well-established to be a significant strategy in developing anti-TB drugs, and Pks13 was identified as a crucial enzyme in this process. Importantly, the modes of action of recognized Pks13 inhibitors differ from traditional anti-TB medications, highlighting Pks13 as a potential and promising target in drug development within TB treatment. In this study, we discovered a compound named BMVC-8C3O that effectively inhibited the activity of Pks13 with a 6.94 μM IC₅₀ value. The binding between BMVC-8C3O and Pks13 was validated through surface plasmon resonance (SPR) assay as well as molecular docking analysis. Moreover, the SPR assay showed that the mutation of Asn1640 and Ser1533 resulted in decreased affinity of BMVC-8C3O to Pks13. Additionally, BMVC-8C3O not only exhibited activity against <em>Mycobacterium tuberculosis</em> (MTB), but also displayed potential intracellular anti-TB activity in macrophages. In summary, our findings indicate that BMVC-8C3O holds great potential as a lead compound against TB.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102579"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}