TuberculosisPub Date : 2025-03-01DOI: 10.1016/j.tube.2025.102626
Weile Xie , Dan Luo , Mingqing Wu , Yicheng Sun , Zhe Wang
{"title":"The evaluation of Phenylalanine-tRNA ligase beta unit (PheT), as a potential target in Mycobacterium abscessus","authors":"Weile Xie , Dan Luo , Mingqing Wu , Yicheng Sun , Zhe Wang","doi":"10.1016/j.tube.2025.102626","DOIUrl":"10.1016/j.tube.2025.102626","url":null,"abstract":"<div><div><em>Mycobacterium abscessus</em> (<em>M. abscessus</em>) is an emerging pathogenic mycobacterium that mainly causes pulmonary infections, especially in immunocompromised patients. This bacterium shows exhibits intrinsic resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and clinicians, thereby raising the need for innovative drug discovery. In this study, we selected phenylalanine-tRNA ligase beta unit (<em>PheT</em>) as a model target and used CRISPR interference to evaluate its essentiality as a therapeutic target against <em>M. abscessus</em>. The results show that genetically disruption of <em>PheT</em> leads to clear growth inhibitory phenotypes both <em>in vitro</em> and <em>in vivo</em>. Further transcriptome analysis revealed differential expression of host genes in response to <em>PheT</em> gene silencing, including genes involved in the cell cycle, apoptotic signaling, and inflammatory responses. Overall, <em>PheT</em> gene plays a crucial role in <em>M. abscessus</em> infection, and its silencing may represent a druggable therapeutic strategy for treating this infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102626"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534828","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}
TuberculosisPub Date : 2025-02-24DOI: 10.1016/j.tube.2025.102619
Katharina Budde , Christoph Lange , Maja Reimann , Nika Zielinski , Lennard Meiwes , Niklas Köhler
{"title":"A novel method for detecting Lipoarabinomannan in urine with the promise of meeting the WHO target product profile for the diagnosis of tuberculosis","authors":"Katharina Budde , Christoph Lange , Maja Reimann , Nika Zielinski , Lennard Meiwes , Niklas Köhler","doi":"10.1016/j.tube.2025.102619","DOIUrl":"10.1016/j.tube.2025.102619","url":null,"abstract":"<div><div>The diagnosis of tuberculosis largely relies on the detection of <em>Mycobacterium tuberculosis (M. tuberculosis)</em> via pathogen-specific DNA or bacterial culture from sputum samples. As the only point-of-care test so far, urinary lipoarabinomannan (LAM) has been endorsed by the World Health Organization for the diagnosis of tuberculosis in people living with HIV.</div><div>In this study, the electrochemiluminescence LAM research assay (EclLAM) was used to measure LAM in the urine of HIV-sero-negative individuals with pulmonary tuberculosis and to monitor anti-tuberculosis treatment. Urine samples from 18 patients with microbiologically confirmed tuberculosis were analyzed before and after the initiation of anti-tuberculosis therapy and 17 healthy controls via the S4-20/A194-01 antibody pair.</div><div>The assay identified 13/18 (72.2 %) patients with tuberculosis and was negative in 17/17 (100.0 %) controls (AUC 0.88). The results of the reactive urine LAM tests correlated with the detection of <em>M. tuberculosis</em> growth in culture (r = 0.94, p < 0.05).</div><div>In conclusion, the LAM-specific antibody assay is promising to fulfill the WHO target product profile for the diagnosis of tuberculosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102619"},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552987","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":"Rv3371, a triacylglycerol synthase promotes survival of Mycobacterium tuberculosis in the host through its contributions to redox homeostasis and propionate detoxification","authors":"Rahul Kumar Maurya , Sarah Fatima , Swati Anand , Rajmani Raju , Suman Bharti , Shivangi Rastogi , Umamageswaran Venugopal , Amitava Sinha , Amit Singh , Manju Y. Krishnan","doi":"10.1016/j.tube.2025.102617","DOIUrl":"10.1016/j.tube.2025.102617","url":null,"abstract":"<div><div>Triacylglycerol (TAG) is the major storage lipid of mycobacteria. <em>Mycobacterium tuberculosis</em> (Mtb) genome encodes 15 triacylglycerol synthases (Tgs), which are speculated to differ in substrate preference, suggesting specific physiological roles. In this study, we investigated the role of a Tgs, Rv3371, in the context of infection. <em>Rv3371</em> knock-out (KO) Mtb was attenuated in mice, with corresponding poor fitness inside macrophages. The KO was more sensitive to free long-chain fatty acids, but was more tolerant to oxidative and nitrosative stresses. Enzyme kinetics of Rv3371 showed its preference for propionyl-CoA. Excess propionate in growth medium retarded the growth of the KO more significantly than the wild type and complemented mutant. This suggests an additional role of Rv3371 in reducing toxic levels of propionate in Mtb by synthesising propionyl TAG. Moreover, chemical inhibition of methylcitrate cycle caused a decrease in methyl-branched lipids in the KO. Overall, the results suggest a role of Rv3371 in Mtb survival in the host through its roles beyond TAG storage.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102617"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511327","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":"Functional and mechanistic insights into the stealth protein full-length CpsY is conducive to understanding immune evasion mechanisms by Mycobacterium tuberculosis","authors":"Dafeng Liu , Ablikim Abdiriyim , Lvxia Zhang , Buayxam Ruzitohti","doi":"10.1016/j.tube.2025.102616","DOIUrl":"10.1016/j.tube.2025.102616","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) is a crucial and destructive intracellular pathogen responsible for causing tuberculosis (TB), a disease of substantial morbidity and mortality. <em>Mtb</em> capsular polysaccharides can misdirect the host's immune response pathways, resulting in additional challenges in TB treatment. These capsule polysaccharides are biosynthesized by a series of stealth proteins including CpsY. Our prior investigations elucidated the structural and functional information of the central domain (aa 201–520) of CpsY within <em>Mtb</em>. However, within the host milieu, it is the full-length iteration of CpsY, rather than its truncated form CpsY<sup>201-520</sup>, that assumes pivotal roles in immune evasion. Consequently, investigating the functional mechanism of full-length CpsY is extremely important. Here, we found that the indispensable role of four conserved regions (CR1-CR4) in governing the phosphotransferase activity of full-length CpsY. Notably, the deletion of S2 (ΔS2) dramatically increased the activity compared to the wild-type (WT) full-length CpsY, thereby revealing S2 in the regulatory dynamics governing the inactivation and activation of full-length CpsY. The gene <em>cpsY</em> helps <em>Mtb</em> to survive in macrophages. Our findings were useful for the development of vaccines and immunotherapies targeting <em>Mtb</em>.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102616"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463837","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}
TuberculosisPub Date : 2025-02-13DOI: 10.1016/j.tube.2025.102615
Swati Jaiswal , Samreen Fatima , Erandi Velarde de la Cruz , Satyendra Kumar
{"title":"Unraveling the role of the immune landscape in tuberculosis granuloma","authors":"Swati Jaiswal , Samreen Fatima , Erandi Velarde de la Cruz , Satyendra Kumar","doi":"10.1016/j.tube.2025.102615","DOIUrl":"10.1016/j.tube.2025.102615","url":null,"abstract":"<div><div>Despite significant advances in research over the past century, Tuberculosis (TB) remains a formidable global health concern. TB granulomas are organized structures composed of immune cells, that serve as the body's primary defense against the spread of <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). The immune landscape of TB granulomas involves a complex array of immune cells, including CD4<sup>+</sup> and CD8<sup>+</sup> T cells, B cells, NK cells, and others, which collectively influence the fate of the granuloma. B cells contribute to the formation of the granuloma's germinal center, while the functional state of T cells—particularly their ability to control infection—dictates whether the granuloma is controlling or proliferative. The intricate interplay between T cells and the dynamic microenvironment of the granuloma plays a pivotal role in determining the outcome of the infection. However, several aspects of the immunological basis of tuberculosis are still unknown. This review delves into the immunological landscape of TB granuloma, focusing on the dynamic cellular interplay within the granuloma and its profound influence on disease pathogenesis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102615"},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511317","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}
TuberculosisPub Date : 2025-02-11DOI: 10.1016/j.tube.2025.102614
Qingqiu Zeng , Zhaowei Tong , Jianfeng Zhong , Xiaofeng Li , Bin Shen , Haiyan Chen , Dating Ge
{"title":"The correlation between immune profiles and pathological changes in pulmonary tuberculosis granulomas revealed by bioinformatic analysis and experimental validation","authors":"Qingqiu Zeng , Zhaowei Tong , Jianfeng Zhong , Xiaofeng Li , Bin Shen , Haiyan Chen , Dating Ge","doi":"10.1016/j.tube.2025.102614","DOIUrl":"10.1016/j.tube.2025.102614","url":null,"abstract":"<div><div>Most of Mycobacterium tuberculosis(Mtb) infection result in the formation of granulomas, which are often rich in immune cells, with subsequent clinical symptoms. However, the role of the immune system in the formation of tuberculosis granuloma structures has not been fully revealed. Here we first analyzed single-cell transcriptome and microenvironment spatial characteristics to reveal the contribution of immune cells to granuloma expansion with validation by immunofluorescence. We then integrated published peripheral blood transcriptome data for Mtb-infected patients and healthy controls. Immune cell profiles were deconvoluted and results were validated on a local cohort using flow cytometry. At the same time, an in-depth evaluation of the changes in the population and function of multiple peripheral blood immune cells during tuberculosis infection were conducted to define correlation with granuloma area. Finally, we screened 6 cytokines (IL6, IL8, IL10, IFNγ, TNFα, TGFβ) through machine learning bioinformatics and analyzed their correlation with the size of tuberculosis granuloma. Based on these findings, we confirmed that the dynamic variation in proportion of immune cells in peripheral blood and the levels of cytokine profiles are closely related to the occurrence and development of tuberculosis granuloma. This study provides a theoretical basis for the molecular mechanism of tuberculosis granuloma.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102614"},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474762","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}
TuberculosisPub Date : 2025-02-06DOI: 10.1016/j.tube.2025.102613
Raquel S.B. Câmara , Isabela A.G. Pereira , Geise C. Espíndola , Daniela P. Lage , Ana L. Silva , Camila S. Freitas , Bárbara P.N. Assis , Laís V.A. Corrêa , Ricardo L.F. Moreira , Sandra Lyon , Rozana C. Silva , Tiago S. Barros , Ana Laura G. de Oliveira , Fernanda Ludolf , Miguel A. Chávez-Fumagalli , Myron Christodoulides , Ricardo A. Machado-de-Ávila , Unaí Tupinambás , Denise U. Gonçalves , Manoel O. da Costa Rocha , Ana T. Chaves
{"title":"Urine-based ELISA using a recombinant chimeric protein for the diagnosis of paucibacillary and multibacillary leprosy","authors":"Raquel S.B. Câmara , Isabela A.G. Pereira , Geise C. Espíndola , Daniela P. Lage , Ana L. Silva , Camila S. Freitas , Bárbara P.N. Assis , Laís V.A. Corrêa , Ricardo L.F. Moreira , Sandra Lyon , Rozana C. Silva , Tiago S. Barros , Ana Laura G. de Oliveira , Fernanda Ludolf , Miguel A. Chávez-Fumagalli , Myron Christodoulides , Ricardo A. Machado-de-Ávila , Unaí Tupinambás , Denise U. Gonçalves , Manoel O. da Costa Rocha , Ana T. Chaves","doi":"10.1016/j.tube.2025.102613","DOIUrl":"10.1016/j.tube.2025.102613","url":null,"abstract":"<div><div>Leprosy diagnosis is difficult to perform due to variable sensitivity and/or specificity of the tests. In addition, the collection of the blood samples requires laboratorial structure and trained professionals. In the present study, the diagnostic efficacy of M1 chimeric protein, which was recently showed to be antigenic for leprosy using a serum-based ELISA, was evaluated against patient urine. Paired serum and urine samples were collected from patients with paucibacillary (PB) and multibacillary (MB) leprosy, tegumentary and visceral leishmaniasis, tuberculosis, Chagas disease, malaria, and HIV-infected subjects. Samples from healthy individuals and household contacts were also used. The protein and peptides used to compose it were used as antigens, and results showed that the four peptides presented good sensitivity and specificity to detect MB leprosy, while M1 protein showed sensitivity and specificity of 98.5 % and 100 %, respectively, to detect both PB and MB leprosy, when an urine-based ELISA was performed. Positive (PPV) and negative (NPV) predictive values were 100 % and 98.3 %, respectively. In a serum-based ELISA, sensitivity and specificity were 96.9 % and 100 %, respectively, with PPV and NPV of 100 % and 96.5 %, respectively. In conclusion, preliminary data suggest that M1 protein could be considered for diagnosis of leprosy by using patient urine.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102613"},"PeriodicalIF":2.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350107","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}
TuberculosisPub Date : 2025-01-31DOI: 10.1016/j.tube.2025.102612
Sara C. Auld , Artur T.L. Queiroz , Mariana Araujo-Pereira , Pholo Maenetje , Nomsa Mofokeng , Lerato Mngomezulu , Duduzile Masilela , Brian Dobosh , Rabindra Tirouvanziam , Hardy Kornfeld , Bruno B. Andrade , Gregory P. Bisson
{"title":"Inflammatory profiles in sputum and blood of people with TB with and without HIV coinfection","authors":"Sara C. Auld , Artur T.L. Queiroz , Mariana Araujo-Pereira , Pholo Maenetje , Nomsa Mofokeng , Lerato Mngomezulu , Duduzile Masilela , Brian Dobosh , Rabindra Tirouvanziam , Hardy Kornfeld , Bruno B. Andrade , Gregory P. Bisson","doi":"10.1016/j.tube.2025.102612","DOIUrl":"10.1016/j.tube.2025.102612","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102612"},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177297","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}
TuberculosisPub Date : 2025-01-26DOI: 10.1016/j.tube.2025.102610
Elizna Maasdorp , Yonas Ghebrekristos , Amanda Khumalo , Lynthia Paul , Monique J. Williams
{"title":"Non-tuberculosis mycobacteria identified by line probe assays in respiratory and non-respiratory samples in South Africa between 2015 and 2019","authors":"Elizna Maasdorp , Yonas Ghebrekristos , Amanda Khumalo , Lynthia Paul , Monique J. Williams","doi":"10.1016/j.tube.2025.102610","DOIUrl":"10.1016/j.tube.2025.102610","url":null,"abstract":"<div><div>In recent years, a rise in non-tuberculosis mycobacteria pulmonary disease (NTM-PD) has been reported in several countries. However, data for high-burden tuberculosis settings, including South Africa, is currently limited. In this study, we conducted a retrospective analysis of routine diagnostic data obtained from one diagnostic laboratory in South Africa between 2015 and 2019. During this period, samples from 275 individuals with suspected mycobacterial infection were tested using the GenoType Mycobacterium CM (Common mycobacteria) or AS (Additional species) line probe assay (LPA) (Brucker-Hain Life science, Nehren, Germany), yielding an NTM-positive result for 163 of these individuals. Interestingly, the positivity rate in respiratory samples declined from 93 % in 2015 to 79 % in 2019. Just over half of the positive samples were of respiratory origin, and the most common species identified in respiratory samples was <em>Mycobacterium intracellulare</em>/<em>Mycobacteium avium</em> complex (28.9 %), followed by <em>M</em>. <em>avium</em> (17.4 %). Where the mycobacterial species was not identified by the LPA, a higher proportion of the subsequent cultures were negative, suggestive of colonisation rather than infection. More than half of patients with a positive NTM-LPA were HIV positive (55.9 %), and this association declined slightly during the study period (62.5 %–50 %).</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102610"},"PeriodicalIF":2.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068177","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}
TuberculosisPub Date : 2025-01-22DOI: 10.1016/j.tube.2025.102609
C Kanipe , EJ Putz , MV Palmer
{"title":"Differential expression of vascular endothelial growth factor A (VEGFA) and M1 macrophage marker nitric oxide synthase 2 (NOS2) in lymph node granulomas of BCG-vaccinated and non-vaccinated cattle infected with Mycobacterium bovis","authors":"C Kanipe , EJ Putz , MV Palmer","doi":"10.1016/j.tube.2025.102609","DOIUrl":"10.1016/j.tube.2025.102609","url":null,"abstract":"<div><div>Bovine tuberculosis is mainly caused by <em>Mycobacterium bovis</em>. Bacillus Calmette-Guérin (BCG) is an attenuated strain of <em>M. bovis</em> which provides variable disease protection. Lesions have been characterized in infected cattle, but little comparison has been done with lesions which form in BCG-vaccinates. Here, <em>in situ</em> hybridization examined differences in expression of <em>M. bovis</em> RNA, inducible nitric oxide synthase 2, and vascular endothelial growth factor A in relation to vaccination status and granuloma grade, using two different groups of cattle. Data found no differences between vaccination groups or granuloma grade in average copies of <em>M. bovis</em> mRNA per μm<sup>2</sup> of total granuloma area or per μm<sup>2</sup> of necrotic areas. Within a vaccination group high-grade granulomas had more NOS2 per cell, per μm<sup>2</sup> and a higher percentage of cells expressing NOS2 than low-grade granulomas. Non-vaccinates had a higher percentage of cells producing NOS2 than vaccinates. Differences in NOS2 expression varied by group. Vaccination status and granuloma grade did not affect the average copies of VEGFA per cell or the percent of cells expressing RNA, however VEGFA copies per μm<sup>2</sup> varied between groups. These findings suggest NOS2 and VEGFA are likely not mechanisms of BCG vaccination protection but may impact disease severity.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102609"},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042374","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}