Tuberculosis最新文献

{"title":"Serodiagnosis of paucibacillary and multibacillary leprosy using a recombinant chimeric protein composed of specific B-cell epitopes derived from Mycobacterium leprae proteins","authors":"Bárbara P.N. Assis ,&nbsp;Ana T. Chaves ,&nbsp;Daniela P. Lage ,&nbsp;Mariana M. Cardoso ,&nbsp;Camila S. Freitas ,&nbsp;Isabela A.G. Pereira ,&nbsp;Raquel S.B. Câmara ,&nbsp;Vívian T. Martins ,&nbsp;Ana Laura G. de Oliveira ,&nbsp;Ricardo A. Machado-de-Ávila ,&nbsp;Alexsandro S. Galdino ,&nbsp;Miguel A. Chávez-Fumagalli ,&nbsp;Myron Christodoulides ,&nbsp;Denise U. Gonçalves ,&nbsp;Lílian L. Bueno ,&nbsp;Ricardo T. Fujiwara ,&nbsp;Eduardo A.F. Coelho ,&nbsp;Manoel O. da Costa Rocha","doi":"10.1016/j.tube.2024.102505","DOIUrl":"10.1016/j.tube.2024.102505","url":null,"abstract":"<div><p>Leprosy diagnosis is difficult due to the clinical similarity with other infectious diseases, and laboratory tests presents problems related to sensitivity and/or specificity. In this study, we used bioinformatics to assess <em>Mycobacterium leprae</em> proteins and formulated a chimeric protein that was tested as a diagnostic marker for the disease. The amino acid sequences from ML0008, ML0126, ML0308, ML1057, ML2028, ML2038, ML2498 proteins were evaluated, and the B-cell epitopes QASVAYPATSYADFRAHNHWWNGP, SLQRSISPNSYNTARVDP and QLLGQTADVAGAAKSGPVQPMGDRGSVSPVGQ were considered <em>M. leprae-</em>specific and used to construct the gene encoding the recombinant antigen. The gene was constructed, the recombinant protein was expressed, purified and tested in ELISA using 252 sera, which contained samples from multibacillary (MB) or paucibacillary (PB) leprosy patients, from their household contacts and healthy individuals, as well as from patients with Chagas disease, visceral and tegumentary leishmaniases (VL/TL), malaria, tuberculosis, and HIV. Sensitivity (Se) and specificity (Sp) for MB and PB samples compared to sera from both healthy subjects and individuals with cross-reactive diseases were 100%. The Se value for MB and PB samples compared to sera from household contacts was 100%, but Sp was 64%. In conclusion, data suggest that this protein could be considered in future studies for leprosy diagnosis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102505"},"PeriodicalIF":3.2,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403957","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":"Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis","authors":"Kusum Sharma ,&nbsp;Megha Sharma ,&nbsp;Ritu Shree ,&nbsp;Neeraj Singla ,&nbsp;Himanshu Joshi ,&nbsp;Tanish Modi ,&nbsp;Manoj Goyal ,&nbsp;Aman Sharma ,&nbsp;Navneet Sharma ,&nbsp;Manish Modi","doi":"10.1016/j.tube.2024.102513","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102513","url":null,"abstract":"<div><h3>Setting and objective</h3><p>To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB.</p></div><div><h3>Design</h3><p>93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing.</p></div><div><h3>Results</h3><p>Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA.</p></div><div><h3>Conclusion</h3><p>The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102513"},"PeriodicalIF":3.2,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308954","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":"In vitro stimulation with nontuberculous mycobacteria induced a stronger cytokine response in leukocytes isolated from individuals with latent tuberculosis compared to those isolated from active tuberculosis or cystic fibrosis patients","authors":"Hardis Rabe ,&nbsp;Elisabeth Lönnermark ,&nbsp;Ewa Johansson ,&nbsp;Marita Gilljam ,&nbsp;Bodil Jönsson","doi":"10.1016/j.tube.2024.102504","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102504","url":null,"abstract":"<div><p><em>Mycobacterium tuberculosis</em> and opportunistic environmental non-tuberculous mycobacteria (NTM) can cause severe infection. Why latent tuberculosis infection advances to active disease, and why some individuals with cystic fibrosis (CF) develop pulmonary infections with NTM is still poorly understood. The aim of this study was to investigate the effector function of peripheral blood mononuclear cells (PBMC) from individuals with active or latent tuberculosis, individuals with CF with or without pulmonary NTM-infection and healthy controls, by measuring cytokine response to <em>in vitro</em> stimulation with different species of NTMs. The cytokine concentrations of IL-17A, IL-22, IL-23, IL-10, IL12p70 and IFN-γ were measured in PBMC-culture supernatants after stimulation with NTMs. PBMCs from individuals with latent tuberculosis infection showed strong IL-17A, IL-22, and IFN-γ responses compared to individuals with active tuberculosis or CF. IL-10 production was low in both tuberculosis groups compared to the CF groups and controls. This study suggests that IL-17A and IL-22 might be important to keep tuberculosis in a latent phase and that individuals with CF with an ongoing NTM infection seem to have a low cytokine response.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102504"},"PeriodicalIF":3.2,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000301/pdfft?md5=9b6f3279dfc539f0537568007303db8f&pid=1-s2.0-S1472979224000301-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations","authors":"Véronique Dartois ,&nbsp;Tracey L. Bonfield ,&nbsp;Jim P. Boyce ,&nbsp;Charles L. Daley ,&nbsp;Thomas Dick ,&nbsp;Mercedes Gonzalez-Juarrero ,&nbsp;Shashank Gupta ,&nbsp;Igor Kramnik ,&nbsp;Gyanu Lamichhane ,&nbsp;Barbara E. Laughon ,&nbsp;Nicola I. Lorè ,&nbsp;Kenneth C. Malcolm ,&nbsp;Kenneth N. Olivier ,&nbsp;Katherine L. Tuggle ,&nbsp;Mary Jackson","doi":"10.1016/j.tube.2024.102503","DOIUrl":"10.1016/j.tube.2024.102503","url":null,"abstract":"<div><p><em>Mycobacterium abscessus</em>, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. <em>M. abscessus</em> infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs. Current standard-of-care chemotherapy is long, includes multiple oral and parenteral repurposed drugs, and is associated with significant toxicity. The development of more effective oral antibiotics to treat <em>M. abscessus</em> infections has thus emerged as a high priority. While murine models have proven instrumental in predicting the efficacy of therapeutic treatments for <em>M. tuberculosis</em> infections, the preclinical evaluation of drugs against <em>M. abscessus</em> infections has proven more challenging due to the difficulty of establishing a progressive, sustained, pulmonary infection with this pathogen in mice. To address this issue, a series of three workshops were hosted in 2023 by the Cystic Fibrosis Foundation (CFF) and the National Institute of Allergy and Infectious Diseases (NIAID) to review the current murine models of <em>M. abscessus</em> infections, discuss current challenges and identify priorities toward establishing validated and globally harmonized preclinical models. This paper summarizes the key points from these workshops. The hope is that the recommendations that emerged from this exercise will facilitate the implementation of informative murine models of therapeutic efficacy testing across laboratories, improve reproducibility from lab-to-lab and accelerate preclinical-to-clinical translation.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102503"},"PeriodicalIF":3.2,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140197273","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":"Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis","authors":"Lihui Guo ,&nbsp;Stefan-Dan Zaharie ,&nbsp;A. Marceline van Furth ,&nbsp;Nicole N. van der Wel ,&nbsp;Anita E. Grootemaat ,&nbsp;Lin Zhang ,&nbsp;Marianna Bugiani ,&nbsp;Mariana Kruger ,&nbsp;Martijn van der Kuip ,&nbsp;René Lutter","doi":"10.1016/j.tube.2024.102495","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102495","url":null,"abstract":"<div><p>In about 1% of tuberculosis (TB) patients, <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%.</p><p>Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of <em>M. tuberculosis</em> as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with <em>M. tuberculosis</em>. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102495"},"PeriodicalIF":3.2,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000210/pdfft?md5=337589fce39eab955de28d4c7c4fb647&pid=1-s2.0-S1472979224000210-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of MicroRNAs as post transcription regulators of matrix metalloproteinases and their association in tuberculous meningitis","authors":"Apoorva Aggarwal ,&nbsp;Neeraj Singla ,&nbsp;Monidipa Konar ,&nbsp;Maninder Kaur ,&nbsp;Kusum Sharma ,&nbsp;Kajal Jain ,&nbsp;Manish Modi ,&nbsp;Sadhna Sharma","doi":"10.1016/j.tube.2024.102501","DOIUrl":"10.1016/j.tube.2024.102501","url":null,"abstract":"<div><p>Matrix metalloproteinases (MMPs) have a role in driving neuroinflammation in infectious as well as non-infectious diseases; however, recent reports have potentiated the role of microRNAs in regulating MMPs at post-transcriptional levels, leading to dysregulation of crucial MMP functions like tissue remodelling, blood brain barrier integrity, etc. In present study, microRNAs regulating MMPs (MMP2 and MMP3) were selected from database search followed by literature support. Expression of these microRNAs i.e., hsa-miR-495-3p, hsa-miR-132-3p and hsa-miR-21-5p was assessed by RT-PCR and the protein levels of MMPs were assessed by ELISA in the cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) patients, healthy controls (HC) and non-infectious neuroinflammatory disease (NID) patients. The expression of hsa-miR-495-3p and hsa-miR-132-3p showed downregulation in TBM while hsa-miR-21-5p was overexpressed as compared to healthy controls. Moreover, MMP levels were found to be deranged with a significant increase in MMP3 levels in the TBM and NID patients compared to HC group. These observations highlight dysregulated microRNAs (hsa-miR-495-3p, hsa-miR-21-5p and hsa-miR-132-3p) levels might impair the levels of MMPs (MMP2 and MMP3) leading to neuroinflammation in TBM and NID population. These findings can further be applied to target these microRNAs for developing newer treatment modalities for better complication management.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102501"},"PeriodicalIF":3.2,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140071605","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":"METTL3-deficiency m6A-dependently degrades MALAT1 to suppress NLRP3-mediated pyroptotic cell death and inflammation in Mycobacterium tuberculosis (H37Ra strain)-infected mouse macrophages","authors":"Limei Han,&nbsp;Nueramina Tieliwaerdi,&nbsp;Xin Li","doi":"10.1016/j.tube.2024.102502","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102502","url":null,"abstract":"<div><p><em>Mycobacterium tuberculosis</em> (Mtb)-infected macrophages aggravated the development of pulmonary tuberculosis, but its detailed molecular mechanisms are still largely unknown. Here, the mouse primary peritoneal macrophages were infected with the attenuated strain of Mtb H37Ra, and we firstly verified that targeting a novel METTL3/N6-Methyladenosine (m6A)/LncRNA MALAT1/miR-125b/TLR4 axis was effective to suppress pyroptotic cell death in the Mtb-infected macrophages. Specifically, through performing Real-Time qPCR and Western Blot analysis, we validated that METTL3, LncRNA MALAT1 and TLR4 were elevated, whereas miR-125b and the anti-oxidant agents (Nrf2 and HO-1) were downregulated in Mtb-infected mouse macrophages. In addition, functional experiments confirmed that both ROS scavenger NAC and METTL3-ablation downregulated NLRP3, GSDMD-C, cleaved Caspase-1 and ASC to restrain pyroptotic cell death and decreased the expression levels of IL-1β, IL-18, IL-6 and TNF-α to restrain inflammatory cytokines expression in Mtb-infected macrophages. Next, METTL3-ablation induced m6A-demethylation and instability in LncRNA MALAT1, and low-expressed LncRNA MALAT1 caused TLR4 downregulation through sponging miR-125b, resulting in the inactivation of NLRP3 inflammasome. Finally, silencing of METTL3-induced protective effects in Mtb-infected macrophages were all abrogated by overexpressing LncRNA MALAT1 and downregulating miR-125b. Thus, we concluded that targeting METTL3-mediated m6A modifications suppressed Mtb-induced pyroptotic cell death in mouse macrophages, and the downstream LncRNA MALAT1/miR-125b/TLR4 axis played critical role in this process.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102502"},"PeriodicalIF":3.2,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062965","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":"Trends of type 2 diabetes with pulmonary tuberculosis patients,2013–2022, and changes after the coronavirus disease 2019 (COVID-19) pandemic","authors":"Zijian Wang ,&nbsp;Sheng Zhao ,&nbsp;Aiping Zhang ,&nbsp;Bin Quan,&nbsp;Chun Duan,&nbsp;Manman Liang,&nbsp;Janghua Yang","doi":"10.1016/j.tube.2024.102499","DOIUrl":"10.1016/j.tube.2024.102499","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;To describe the trends of Type 2 Diabetes with Pulmonary Tuberculosis (T2DM-TB) patients from 2013 to 2022 and to investigate the impact of COVID-19 lockdown on glycemic control and associated factors in T2DM-TB.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this population-based study of the First Affiliated Yijishan Hospital of Wannan Medical College in China, we described the 10-year trends of patients diagnosed with T2DM-TB. We included patients diagnosed with TB, T2DM-TB and T2DM-TB patients for comparative analysis, aged 15 years or older. Data were missing, and both multidrug-resistant (MDR) TB patients and non-T2DM patients were excluded from our study.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We pooled Type 2 Diabetes (T2DM) and Tuberculosis (TB) data from The First Affiliated Yijishan Hospital of Wannan Medical College in China, gathered between January 1, 2013, and December 31, 2022. The data included 14,227 T2DM patients, 6130 TB patients, and 982 T2DM-TB patients. During the past 10 years, the number of inpatients with TB decreased, while the number of patients with T2DM and T2DM-TB increased year by year. To rule out any influence factors, we analyzed the ratio of the three groups. The ratio of TB/T2DM decreased year by year (p &lt; 0.05), while the ratio of TB-T2DM/TB increasing year by year (p = 0.008). During the COVID-19 epidemic period, there was no significant change in the ratio of TB-T2DM/T2DM (p = 0.156). There was no significant change in the proportion of male patients with TB and TB-T2DM (p = 0.325; p = 0.190), but the proportion of male patients with T2DM showed an increasing trend (p &lt; 0.001). The average age of TB patients over the past 10 years was 54.5 ± 18.4 years and showed an increasing trend year by year (p &lt; 0.001). However, there was no significant change in the age of T2DM or TB-T2DM patients (p = 0.064; p = 0.241). Patients data for the first (2013–2017) and the last (2018–2022) five years were compared. We found that the number of T2DM and TB-T2DM in the last five years was significantly higher than in the first five years, but the number of TB was significantly lower than in the first five years. There is a significant statistical difference in the proportion of TB/T2DM and TB-T2DM/TB, which is similar to the previous results. The average age (56.0 ± 17.6 years) of TB patients in the last five years is significantly higher than in the first five years (53.1 ± 18.9) (p &lt; 0.001). The number of male patients with T2DM in the last five years is higher than that in the first five years, with significant difference (p &lt; 0.001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The trends of T2DM-TB among hospitalized TB patients have increased significantly over the past 10 years, which may be related to the increase in the number of T2DM cases. The COVID-19 pandemic has been effective in controlling the transmission of TB, but it has been detrimental to the control of T2DM. Male patients with T2DM and el","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102499"},"PeriodicalIF":3.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000258/pdfft?md5=f6763ace09806162da3a641c584d5040&pid=1-s2.0-S1472979224000258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational drug repositioning identifies niclosamide and tribromsalan as inhibitors of Mycobacterium tuberculosis and Mycobacterium abscessus","authors":"Jeremy J. Yang ,&nbsp;Aaron Goff ,&nbsp;David J. Wild ,&nbsp;Ying Ding ,&nbsp;Ayano Annis ,&nbsp;Randy Kerber ,&nbsp;Brian Foote ,&nbsp;Anurag Passi ,&nbsp;Joel L. Duerksen ,&nbsp;Shelley London ,&nbsp;Ana C. Puhl ,&nbsp;Thomas R. Lane ,&nbsp;Miriam Braunstein ,&nbsp;Simon J. Waddell ,&nbsp;Sean Ekins","doi":"10.1016/j.tube.2024.102500","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102500","url":null,"abstract":"<div><p>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 <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>). 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. <em>Mycobacterium abscessus (M. abscessus)</em> 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 (<em>M. tuberculosis</em> IC₉₀ 2.95 μM; <em>M. abscessus</em> IC₉₀ 59.1 μM) and tribromsalan (<em>M. tuberculosis</em> IC₉₀ 76.92 μM; <em>M. abscessus</em> IC₉₀ 147.4 μM) inhibit <em>M. tuberculosis</em> and <em>M. abscessus in vitro</em>. To investigate the mode of action, we determined the transcriptional response of <em>M. tuberculosis</em> and <em>M. abscessus</em> to both compounds in axenic log phase, demonstrating a broad effect on gene expression that differed from known <em>M. tuberculosis</em> inhibitors. Both compounds elicited transcriptional responses indicative of respiratory pathway stress and the dysregulation of fatty acid metabolism.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102500"},"PeriodicalIF":3.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S147297922400026X/pdfft?md5=55713d804b4f2ee2b52938a2411c9b61&pid=1-s2.0-S147297922400026X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment","authors":"Febriana Catur Iswanti ,&nbsp;Kurnia Maidarmi Handayani ,&nbsp;Ardiana Kusumaningrum ,&nbsp;Tomohiko Yamazaki ,&nbsp;Diah Handayani ,&nbsp;Mohamad Sadikin","doi":"10.1016/j.tube.2024.102498","DOIUrl":"10.1016/j.tube.2024.102498","url":null,"abstract":"<div><p>Drug resistance to tuberculosis (TB) has become an obstacle in eliminating tuberculosis. The transmission of drug-resistant TB from patients increases the incidence of primary drug-resistant (DR) TB in individuals who are in close contact. Therefore, it is necessary to incorporate an immunological approach into preventive therapy. This study focuses on the activity of lysosomal enzymes, oxygen bursts, and the attachment ability of macrophages among individuals diagnosed with active drug-resistant TB compared with close contacts with latent TB or healthy cases. We measured macrophage oxygen burst ability (Water-soluble tetrazolium salt (WST) test, Nitric Oxide production, and myeloperoxidase activity) and the degradative ability of lysosomes (activity of the β-glucuronidase and acid phosphatase enzymes). Six active DR-TB patients and 18 close-contact cases (8 Latent Tuberculosis Infection (LTBI); 10 healthy) were recruited at Universitas Indonesia Hospital. The macrophage attachment of the LTBI group was higher than in the other groups. NO production, myeloperoxidase activity, β-glucuronidase, and acid phosphatase were higher in the active DR-TB group. A negative correlation was uncovered between phagocytosis and NO production, myeloperoxidase activity, and lysosomal enzymes. The difference in macrophage function is expected to be a further reference in active DR-TB treatment or preventive therapy.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102498"},"PeriodicalIF":3.2,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000246/pdfft?md5=15ba43fa91118601eebf75ab840f7b87&pid=1-s2.0-S1472979224000246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}