Tuberculosis最新文献

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IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa 撒哈拉以南非洲不同地理区域人群对毛卷曲结核分枝杆菌(MTP)的IgG抗体反应
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1016/j.tube.2025.102634
Koobashnee Pillay , Theresa Coetzer , Catherine Connolly , Balakrishna Pillay , Thamsanqa Chiliza , Kogieleum Naidoo , Jayne Sutherland , Thumbi Ndung'u , Harriet Mayanja-Kizza , Manormoney Pillay
{"title":"IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa","authors":"Koobashnee Pillay ,&nbsp;Theresa Coetzer ,&nbsp;Catherine Connolly ,&nbsp;Balakrishna Pillay ,&nbsp;Thamsanqa Chiliza ,&nbsp;Kogieleum Naidoo ,&nbsp;Jayne Sutherland ,&nbsp;Thumbi Ndung'u ,&nbsp;Harriet Mayanja-Kizza ,&nbsp;Manormoney Pillay","doi":"10.1016/j.tube.2025.102634","DOIUrl":"10.1016/j.tube.2025.102634","url":null,"abstract":"<div><div>Previously, a slot blot or an indirect enzyme-linked immunosorbent assay (ELISA) using a synthetic or purified MTP antigen, conceptually demonstrated IgG antibody induction in pulmonary TB patients, albeit with small sample sizes and differing sensitivity. Therefore, we evaluated an IgG MTP ELISA in larger populations from The Gambia (n = 549), Uganda (n = 161), and South Africa (n = 193), comprising human immunodeficiency virus (HIV) positive and negative, with microbiologically confirmed active TB. The association between the IgG level and demographic characteristics was determined by multivariate logistic regression. The sensitivity (44.8–61.2 %) and specificity (33.4–78.5 %) varied in the three cohorts. Anti-MTP antibody titres differed between the TB positive and negative groups within the South African and The Gambian cohorts (p &lt; 0.001), but not in Uganda (p = 0.35). Antibodies were detected in HIV positive and negative patients and were reduced at 6-month follow-up after treatment (p &gt; 0.067). The study verified previous findings that anti-MTP antibodies, and therefore MTP antigen, are produced during active TB. However, the accuracy of the MTP-IgG ELISA was low, and is therefore not suitable as a target product profile in the high burden TB areas investigated. Further studies are needed to clarify the variable reactivities in different geographical areas.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102634"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714208","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}
引用次数: 0
The anti-mycobacterial potential of ibuprofen 布洛芬的抗分枝杆菌潜能
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1016/j.tube.2025.102638
Pir Tariq Shah , Li Xing
{"title":"The anti-mycobacterial potential of ibuprofen","authors":"Pir Tariq Shah ,&nbsp;Li Xing","doi":"10.1016/j.tube.2025.102638","DOIUrl":"10.1016/j.tube.2025.102638","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen (IBU) is a non-prescription analgesic drug from the non-steroidal anti-inflammatory drug class. It is widely used for treating pain, fever, and inflammation. Both the <em>in silico</em> and <em>in vitro</em> experiments were performed to determine the antibacterial potentials of the IBU against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>).</div></div><div><h3>Methods</h3><div>The STITCH v.5 pipeline was used to analyze the interaction of IBU with the proteome of the <em>Mtb</em> H37Ra and H37Rv strains. The GFP-tagged <em>Bacillus Calmette Guerin</em> (<em>BCG</em>) and td-tomato-tagged <em>Mtb</em> H37Ra were used to determine the bacteriostatic and bactericidal activities of IBU. The IBU-treated THP-1-derived macrophages were infected by td-tomato-tagged <em>Mtb</em> H37Ra and wild-type <em>BCG</em> to analyze the effects of IBU on bacterial phagocytosis and apoptosis, respectively.</div></div><div><h3>Results</h3><div>The <em>in-silico</em> study revealed that the IBU interacts with <em>Mtb</em> proteins primarily involved in cellular process, metabolism, and virulence, and targets four virulent proteins of <em>Mtb</em>, e.g., Cyp-123, Cyp-126, Cyp-130, and Cyp-139 in the cytochrome p450 system. The increasing concentrations of IBU showed significant bacteriostatic activity against <em>Mtb</em> H37Ra <em>in vitro</em>, where the 100 μg/ml and 200 μg/ml concentrations especially led to almost complete bacterial growth arrest. The IBU treatment does not affect <em>BCG</em>-induced apoptosis of THP-1-derived macrophages, but significantly enhances bacterial uptake, especially at 100 μg/ml and 200 μg/ml concentrations.</div></div><div><h3>Conclusions</h3><div>The IBU enhances <em>Mtb</em> uptake by macrophages and exhibits direct bacteriostatic activity <em>in vitro</em>.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102638"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783156","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}
引用次数: 0
Unraveling the role of the immune landscape in tuberculosis granuloma 揭示免疫景观在结核肉芽肿中的作用
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-02-13 DOI: 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 ,&nbsp;Samreen Fatima ,&nbsp;Erandi Velarde de la Cruz ,&nbsp;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":"2025-05-01","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}
引用次数: 0
Rv3371, a triacylglycerol synthase promotes survival of Mycobacterium tuberculosis in the host through its contributions to redox homeostasis and propionate detoxification Rv3371是一种三酰基甘油合成酶,它通过氧化还原稳态和丙酸解毒促进宿主结核分枝杆菌的存活
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-02-21 DOI: 10.1016/j.tube.2025.102617
Rahul Kumar Maurya , Sarah Fatima , Swati Anand , Rajmani Raju , Suman Bharti , Shivangi Rastogi , Umamageswaran Venugopal , Amitava Sinha , Amit Singh , Manju Y. Krishnan
{"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 ,&nbsp;Sarah Fatima ,&nbsp;Swati Anand ,&nbsp;Rajmani Raju ,&nbsp;Suman Bharti ,&nbsp;Shivangi Rastogi ,&nbsp;Umamageswaran Venugopal ,&nbsp;Amitava Sinha ,&nbsp;Amit Singh ,&nbsp;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":"2025-05-01","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}
引用次数: 0
The correlation between immune profiles and pathological changes in pulmonary tuberculosis granulomas revealed by bioinformatic analysis and experimental validation 免疫谱与肺结核肉芽肿病理变化的相关性:生物信息学分析与实验验证
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-02-11 DOI: 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 ,&nbsp;Zhaowei Tong ,&nbsp;Jianfeng Zhong ,&nbsp;Xiaofeng Li ,&nbsp;Bin Shen ,&nbsp;Haiyan Chen ,&nbsp;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":"2025-05-01","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}
引用次数: 0
Response to “Prevalence of non-tuberculous mycobacteria by Line-Probe Assay” 对“线探针法检测非结核分枝杆菌患病率”的回应
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1016/j.tube.2025.102637
Elizna Maasdorp , Monique J. Williams
{"title":"Response to “Prevalence of non-tuberculous mycobacteria by Line-Probe Assay”","authors":"Elizna Maasdorp ,&nbsp;Monique J. Williams","doi":"10.1016/j.tube.2025.102637","DOIUrl":"10.1016/j.tube.2025.102637","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102637"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786188","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}
引用次数: 0
Prevalence of non-tuberculous mycobacteria estimated by line-probe assay 用线探针法估计非结核分枝杆菌的患病率
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1016/j.tube.2025.102636
Sarman Singh
{"title":"Prevalence of non-tuberculous mycobacteria estimated by line-probe assay","authors":"Sarman Singh","doi":"10.1016/j.tube.2025.102636","DOIUrl":"10.1016/j.tube.2025.102636","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102636"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738965","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}
引用次数: 0
Functional analysis of genetic mutations in ddn and fbiA linked to delamanid resistance in rifampicin-resistant Mycobacterium tuberculosis 耐利福平结核分枝杆菌中与德拉曼耐药相关的ddn和fbiA基因突变的功能分析
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI: 10.1016/j.tube.2025.102630
Seungmo Kim , Seung Heon Lee , Gisu Kang , Gyeong In Lee , Hyeon-Su Kim , Jeong Seong Yang , Youngsuk Park , Byoung Oh Hwang , Hyejin Kim
{"title":"Functional analysis of genetic mutations in ddn and fbiA linked to delamanid resistance in rifampicin-resistant Mycobacterium tuberculosis","authors":"Seungmo Kim ,&nbsp;Seung Heon Lee ,&nbsp;Gisu Kang ,&nbsp;Gyeong In Lee ,&nbsp;Hyeon-Su Kim ,&nbsp;Jeong Seong Yang ,&nbsp;Youngsuk Park ,&nbsp;Byoung Oh Hwang ,&nbsp;Hyejin Kim","doi":"10.1016/j.tube.2025.102630","DOIUrl":"10.1016/j.tube.2025.102630","url":null,"abstract":"<div><div>The connection between genetic mutations linked to delamanid resistance and phenotypic resistance remains unclear. We assessed the phenotypic effects of delamanid-resistant mutations in the <em>Mycobacterium tuberculosis</em> H37Rv strain through gene disruption using homologous recombination and complementation tests. Delamanid resistance was assessed by determining the minimum inhibitory concentration (MIC) via the 7H9 microdilution method. Sanger sequencing identified mutations, and conservation of the mutated residues was predicted through multiple sequence alignments of orthologs. A total of 116 isolates with MIC ≥0.025 μg/mL were analyzed, among which mutations were identified in the <em>ddn</em> and <em>fbiA</em> genes. Isogenic strains were generated based on these mutations. The <em>ddn</em> or <em>fbiA</em> isogenic strains with Ala77Val, Gly81Ser, Asn25fs, and Leu104Phe in <em>fbiA</em> had MICs ≥0.8 μg/mL, indicating resistance. In contrast, the <em>ddn</em> isogenic strain with Pro12Ala had an MIC of 0.012 μg/mL, showing susceptibility, while Gly96Asp in <em>fbiA</em> had an MIC of 0.1 μg/mL, indicating resistance. All mutations, except for Pro12Ala, were conserved in the protein sequences of both FbiA and Ddn and their mycobacterial orthologs. The characterization of these mutations provides insights into the mechanisms of delamanid resistance, which may inform the development of optimized treatment strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102630"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680656","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}
引用次数: 0
Customized MHC Class I & II restricted peptides from clinical isolates of Mycobacterium tuberculosis tweak strong cellular immune response in Healthy individuals and Pulmonary Tuberculosis patients: A potential candidate in vaccine design 从结核分枝杆菌临床分离株中定制的MHC I类和II类限制性肽在健康个体和肺结核患者中改变了强烈的细胞免疫反应:疫苗设计的潜在候选物
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-05-01 Epub Date: 2025-04-15 DOI: 10.1016/j.tube.2025.102640
Niharika Sharma , Beenu Joshi , Bhawna Sharma , Santosh Kumar , Keshar Kunja Mohanty , Hridayesh Prakash
{"title":"Customized MHC Class I & II restricted peptides from clinical isolates of Mycobacterium tuberculosis tweak strong cellular immune response in Healthy individuals and Pulmonary Tuberculosis patients: A potential candidate in vaccine design","authors":"Niharika Sharma ,&nbsp;Beenu Joshi ,&nbsp;Bhawna Sharma ,&nbsp;Santosh Kumar ,&nbsp;Keshar Kunja Mohanty ,&nbsp;Hridayesh Prakash","doi":"10.1016/j.tube.2025.102640","DOIUrl":"10.1016/j.tube.2025.102640","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a global health challenge as annual mortality rate due to drug resistant TB is increasing exponentially. This is mostly associated with the delayed diagnosis of Multidrug-resistant (MDR) or latent TB. Effective management of TB demands development of novel immunological strategies, such as peptide-based/subunit vaccines that can stimulate specific immune responses. In this context, we evaluated the immunogenic potential of two Major Histocompatibility Complex (MHC) Class I/II-restricted peptides from <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>): Rv2588c and Rv0148. The peptides were tested on T and monocyte populations from healthy donors and pulmonary TB (PTB) patients. Flow cytometry analysis revealed significant T cell activation in peripheral blood mononuclear cells (PBMC) from both groups. Enzyme-linked immunosorbent assay (ELISA) demonstrated a strong IFN-γ response, confirming effective T cell activation. Additionally, these peptides induced increased nitric oxide (NO) production in macrophages, indicating their role in activating the innate immune system. Overall, Rv2588c and Rv0148 peptides exhibited robust immunogenicity, stimulating both adaptive and innate immune responses in PBMCs from healthy and PTB individuals. These findings highlight their potential as promising TB vaccine candidates, paving the way for improved TB treatment and prevention strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102640"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851559","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}
引用次数: 0
Fluctuations in circulating cell-free mitochondrial and nuclear DNA copy numbers in blood plasma after anti-tuberculosis drug intake in patients with drug-susceptible tuberculosis 药物敏感结核患者服用抗结核药物后血浆循环无细胞线粒体和核DNA拷贝数的波动
IF 2.8 3区 医学
Tuberculosis Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1016/j.tube.2025.102611
Lauma Freimane , Agnija Kivrāne , Viktorija Ulanova , Anda Vīksna , Eduards Sevostjanovs , Solveiga Grīnberga , Andra Cīrule , Alvils Krams , Renāte Ranka
{"title":"Fluctuations in circulating cell-free mitochondrial and nuclear DNA copy numbers in blood plasma after anti-tuberculosis drug intake in patients with drug-susceptible tuberculosis","authors":"Lauma Freimane ,&nbsp;Agnija Kivrāne ,&nbsp;Viktorija Ulanova ,&nbsp;Anda Vīksna ,&nbsp;Eduards Sevostjanovs ,&nbsp;Solveiga Grīnberga ,&nbsp;Andra Cīrule ,&nbsp;Alvils Krams ,&nbsp;Renāte Ranka","doi":"10.1016/j.tube.2025.102611","DOIUrl":"10.1016/j.tube.2025.102611","url":null,"abstract":"<div><div>Biomarker research characterising the effect of anti-tuberculosis (TB) chemotherapy on systemic body response is still limited. In this study, we aimed to investigate fluctuations in circulating cell-free mitochondrial DNA (ccf-mtDNA) and circulating cell-free nuclear DNA (ccf-nDNA) copy number (CN) in blood plasma of patients with drug-susceptible TB (DS-TB) and to decipher factors related to these fluctuations.</div><div>The results showed considerable changes in ccf-mtDNA CN in plasma samples before drug intake and 2 and 6 h afterwards, with high inter patient variability at each time point. Multivariate linear regression revealed that the dynamics of ccf-mtDNA CN was influenced by patients’ age, ethambutol pharmacokinetics, and body-mass index (BMI); ethambutol exposure emerged as the most significant factor. Very low ccf-nDNA CN in all three time points with little variation was observed; none factors were strongly associated with ccf-nDNA.</div><div>In conclusion, our study revealed the effect of anti-TB chemotherapy, age and BMI on acute changes in circulating ccf-mtDNA CN in blood plasma and highlighted the systemic, mitochondria-related effects of ethambutol in patients with TB. Further studies with larger cohorts are needed to understand the biological relevance of ccf-DNA in patients with TB and to validate its application in TB treatment monitoring.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102611"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042376","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}
引用次数: 0
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