Tuberculosis最新文献

Knockdown of argininosuccinate lyase influences the growth of Mycolicibacterium smegmatis in vitro and in vivo 精氨酸琥珀酸裂解酶的敲低对耻垢分枝杆菌体外和体内生长的影响

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-19 DOI: 10.1016/j.tube.2025.102693

Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang

{"title":"Knockdown of argininosuccinate lyase influences the growth of Mycolicibacterium smegmatis in vitro and in vivo","authors":"Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang","doi":"10.1016/j.tube.2025.102693","DOIUrl":"10.1016/j.tube.2025.102693","url":null,"abstract":"<div><div>The rising prevalence of drug-resistant tuberculosis (DR-TB), coupled with stagnation in the development of novel therapeutics, underscores the urgent need for new drug targets and innovative anti-tuberculosis agents. In this study, we demonstrate that CRISPR interference-mediated knockdown of argH, a nitrogen metabolism-associated gene encoding argininosuccinate lyase, significantly impairs the growth of <em>Mycolicibacterium smegmatis</em> (formerly <em>Mycobacterium smegmatis</em>). This growth defect was alleviated in a concentration-dependent manner by arginine supplementation. In a goldfish infection model, argH knockdown led to a marked reduction in bacterial burden within both liver and kidney tissues. Notably, bacitracin and 5-fluorouracil exhibited synergistic effects when combined with argH knockdown. Metabolomic profiling revealed significant perturbations in multiple amino acids, as well as in succinyl-CoA and lactate levels, suggesting that suppression of argH impairs <em>M. smegmatis</em> proliferation by disrupting amino acid homeostasis and interfering with aerobic respiration.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102693"},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119026","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

Exploring CHIT1 and YKL-40 in tuberculous pleural effusion: Insights and implications 探讨结核性胸腔积液中CHIT1和YKL-40：见解和意义

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-19 DOI: 10.1016/j.tube.2025.102692

Natalia Przysucha , Magdalena Paplińska-Goryca , Katarzyna Górska , Paulina Misiukiewicz-Stępień , Michał Mlącki , Agata Cyran , Rafal Krenke

{"title":"Exploring CHIT1 and YKL-40 in tuberculous pleural effusion: Insights and implications","authors":"Natalia Przysucha , Magdalena Paplińska-Goryca , Katarzyna Górska , Paulina Misiukiewicz-Stępień , Michał Mlącki , Agata Cyran , Rafal Krenke","doi":"10.1016/j.tube.2025.102692","DOIUrl":"10.1016/j.tube.2025.102692","url":null,"abstract":"<div><h3>Background</h3><div>Chitinases and chitinase-like proteins are implicated in the pathophysiology of lung diseases. This study aimed to evaluate the significance of chitotriosidase (CHIT1) and YKL-40 in tuberculous pleural effusion (TPE), identify their cellular sources, and assess their diagnostic potential as TPE biomarkers.</div></div><div><h3>Methods</h3><div>This observational, retrospective study included 66 patients with pleural effusion of different origins: malignant (MPE), tuberculous (TPE), parapneumonic (PPE), and transudative (TE). Pleural fluid levels of YKL-40 and CHIT1 were measured. Expressions of YKL-40 and CHIT1 in tuberculous pleural granulomas were also assessed using immunohistochemical staining.</div></div><div><h3>Results</h3><div>We found the highest median CHIT1 and YKL-40 levels for TPE: 70.51 (interquartile range [IQR] 49.65–136.98) ng/mL and 569.84 (IQR 530.32–706.01) ng/mL, respectively. YKL-40 was significantly higher in TPE than in PPE (387.98 [IQR 262.94–539.09] ng/mL, p < 0.01)] and TE (254.95 [IQR 188.93–334.1 ng/ml] ng/mL, p < 0.001). There was a strong positive correlation between the YKL-40 level in TPE and the percentage of macrophages (r = 0.73, p = 0.003) and the adenosine deaminase activity (r = 0.82, p < 0.001). We revealed strong YKL-40 expression in tuberculoid pleural granulomas.</div></div><div><h3>Conclusion</h3><div>YKL-40, but not CHIT-1, may contribute to the pleural inflammatory response associated with tuberculosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102692"},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109023","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

Whole-genome sequencing-based surveillance system for Mycobacterium tuberculosis in Portugal 基于全基因组测序的葡萄牙结核分枝杆菌监测系统。

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-12 DOI: 10.1016/j.tube.2025.102691

Miguel Pinto , Rita Macedo

{"title":"Whole-genome sequencing-based surveillance system for Mycobacterium tuberculosis in Portugal","authors":"Miguel Pinto , Rita Macedo","doi":"10.1016/j.tube.2025.102691","DOIUrl":"10.1016/j.tube.2025.102691","url":null,"abstract":"<div><div>To improve TB surveillance and diagnosis, the Portuguese National Reference Laboratory (NRL) began implementing whole-genome sequencing (WGS) for all RR/MDR-TB cases in 2019. Since 2020, this approach has been expanded to indiscriminately include all received isolates. We describe the current WGS-based surveillance system in Portugal, framed in prospective and retrospective data (n = 1171), upgraded for antimicrobial resistance (AMR) prediction and epidemiological analysis. This system relies on three main steps: QC/QA and contamination assessment, with a novel data filtering step; genotyping and AMR prediction; and dynamic SNP-based approach, maximizing variable sites under analysis. While lineage 4 was the most prevalent (84.3 %) followed by lineage 2 (9.1 %), less common EU/EEA sub-lineages (e.g., lineages 3 and 6) showcased cross-border transmissions. Molecular clusters (n = 157) displayed distinct AMR profiles and diverse possible epidemiological contexts. Among the pipeline upgrades, we highlight: i) the novel filtering step that allowed the improvement of 123 out of 128 contaminated samples; ii) tolerating missing data per site more than doubled core variable site resolution; iii) automatic maximization of shared variable sites for in-depth cluster analysis, key for consolidating genetic links in epidemiological investigation. This study highlights the importance of sustained prospective genomic surveillance towards strengthening TB management and diagnosis in Portugal.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102691"},"PeriodicalIF":2.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087616","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

Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates 在中间尺度评估基因内的选择为结核分枝杆菌临床分离株的阳性选择提供了强有力的基因鉴定。

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-11 DOI: 10.1016/j.tube.2025.102690

Thomas R. Ioerger, Anthony Shatby

{"title":"Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates","authors":"Thomas R. Ioerger, Anthony Shatby","doi":"10.1016/j.tube.2025.102690","DOIUrl":"10.1016/j.tube.2025.102690","url":null,"abstract":"<div><div>Multiple studies have reported genes in the <em>M. tuberculosis</em> (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) yields the most credible list of candidate genes under selection (excluding PPE and PE_PGRS genes, which are predicted less reliably due to frequent sequencing errors). A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 173 significant genes under selection, with 36 % overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection (<em>resR, phoR</em>). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102690"},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207730","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

M. bovis FadR mutant exhibits an altered colony morphotype and increased virulence 牛分枝杆菌FadR突变体表现出改变的菌落形态和增加的毒力

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-06 DOI: 10.1016/j.tube.2025.102689

Vandana Singh , Mohd Mustkim Ansari , Debashis Dutta , R.S. Rajmani , Amit Singh , Bhupendra N. Singh

{"title":"M. bovis FadR mutant exhibits an altered colony morphotype and increased virulence","authors":"Vandana Singh , Mohd Mustkim Ansari , Debashis Dutta , R.S. Rajmani , Amit Singh , Bhupendra N. Singh","doi":"10.1016/j.tube.2025.102689","DOIUrl":"10.1016/j.tube.2025.102689","url":null,"abstract":"<div><div>FadR, a GntR family transcriptional regulator, is known to maintain fatty acid homeostasis in prokaryotes. In this study, a <em>fadR</em> deletion mutant was generated in <em>Mycobacterium bovis</em>, which exhibited distinct morphological changes, along with enhanced permeability and increased antibiotic susceptibility. Interrupted cell-wall homeostasis often leads to such collateral phenotype. To gain insight into the lipid profile, we conducted lipidomics analysis, which revealed that the levels of DAT and PAT were higher in the mutant, while keto-mycolate methyl esters were lower. Further, key proteins responsible for altered phenotypes and lipid profiles were identified using a comparative proteomics approach between <em>M. bovis</em> and the Δ<em>fadR</em> mutant. In addition to lipid metabolism, several intermediary metabolic and stress response proteins predicted to have roles in the growth, survival, and pathogenicity of mycobacteria were also altered in the mutant. Notably, deletion of <em>fadR</em> led to hypervirulence in the animal model. Taken together, this study establishes a crucial role of FadR in the survival of mycobacteria by regulating lipid metabolism, providing insights into its potential as a target for therapeutic strategies against slow-growing mycobacteria.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102689"},"PeriodicalIF":2.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046233","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

Diagnosis of extrapulmonary tuberculosis by Truenat® MTB/MTB Plus assay 应用Truenat®MTB/MTB Plus检测诊断肺外结核

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-05 DOI: 10.1016/j.tube.2025.102688

Promod K. Mehta, Jefry Sebastian

{"title":"Diagnosis of extrapulmonary tuberculosis by Truenat® MTB/MTB Plus assay","authors":"Promod K. Mehta, Jefry Sebastian","doi":"10.1016/j.tube.2025.102688","DOIUrl":"10.1016/j.tube.2025.102688","url":null,"abstract":"<div><div>Diagnosis of extrapulmonary tuberculosis (EPTB) is challenging. During the last two decades, several nucleic acid amplification tests have been deliberated to diagnose TB (including EPTB) and drug resistance (DR), <em>i.e</em>. in-house PCR/multiplex-PCR, commercial real-time PCR (<em>e.g.</em> Cobas TaqMan/LightCycler), line probe assay (<em>e.g.</em> GenoType MTBDRplus), GeneXpert®/GeneXpert® Ultra and Truenat®MTB/MTB Plus (TruPlus). However, we still need a simple and reliable diagnostic test especially for remote areas. Markedly, both GeneXpert/Xpert Ultra require a constant power supply and their high cost is a major hindrance in resource-limited settings. To overcome this, Molbio Diagnostics, India, introduced a Truenat/TruPlus assay (the WHO endorsed), which is chip-based micro real-time PCR system that targets <em>nrdB</em>, while TruPlus targets IS<em>6110</em>+<em>nrdZ</em> for the identification of <em>Mtb</em> within 1 h. After a positive result, an ‘add-on’ chip, <em>i.e</em>. Truenat® MTB-RIF Dx (TruRif) is utilized to detect rifampicin-resistance (RIF-R) that takes another 1 h. Although there is adequate literature on the diagnosis of pulmonary TB by Truenat/TruPlus, limited information is available on EPTB diagnosis. In this review, we assessed the performance of Truenat/TruPlus in different EPTB types, <em>i.e</em>. TB lymphadenitis, TB pleuritis, TB meningitis, osteoarticular TB, etc. that exhibits moderate to good sensitivity/specificity. Meanwhile, few false negative/positive RIF-R results are obtained by TruRif. Since Truenat/TruPlus is portable, battery-operated and relatively cost-effective as compared to GeneXpert/Xpert Ultra, it can be utilized for preliminary screening of EPTB specimens in peripheral settings, which may be further confirmed by other tests.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102688"},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158213","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

Correspondence on “Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets” 关于“利用49个策划的人类转录组数据集分析结核基因特征的交叉研究可复制性”的通信。

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-01 DOI: 10.1016/j.tube.2025.102677

Hinpetch Daungsupawong , Viroj Wiwanitkit

引用次数: 0

Response to “Correspondence on ‘Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets’” 对“利用49个人类转录组数据集分析结核基因特征的交叉研究可复制性”的通信”的回复。

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-09-01 DOI: 10.1016/j.tube.2025.102678

Xutao Wang , Katie Harper , Pranay Sinha , W. Evan Johnson , Prasad Patil

引用次数: 0

ESAT-6 of Mycobacterium tuberculosis downregulates cofilin1, leads to filamentous actin enrichment and reduces the phagosome acidification in infected macrophages, which are partially reversed by a single methionine mutation 结核分枝杆菌的ESAT-6下调cofilin1，导致丝状肌动蛋白富集并减少感染巨噬细胞的吞噬体酸化，这一过程可通过单个蛋氨酸突变部分逆转

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-08-28 DOI: 10.1016/j.tube.2025.102680

P.P. Mahesh , R.J. Retnakumar , K.C. Sivakumar , Sathish Mundayoor

{"title":"ESAT-6 of Mycobacterium tuberculosis downregulates cofilin1, leads to filamentous actin enrichment and reduces the phagosome acidification in infected macrophages, which are partially reversed by a single methionine mutation","authors":"P.P. Mahesh , R.J. Retnakumar , K.C. Sivakumar , Sathish Mundayoor","doi":"10.1016/j.tube.2025.102680","DOIUrl":"10.1016/j.tube.2025.102680","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>) persists within macrophages by evading phagosome maturation. In this study, we considered the role of actin dynamics in this process. Macrophages infected with virulent <em>M. tuberculosis</em> showed high F-actin/G-actin ratio, accompanied by reduced expression of the actin-depolymerizing protein cofilin1 and increased levels of its inactive phosphorylated form. Overexpression of a constitutively active cofilin1 variant reduced F-actin accumulation and enhanced phagosome acidification. Similar effects were observed with sorafenib, a PI3K-dependent activator of cofilin1, which decreased F-actin levels and promoted phagosome acidification in infected macrophages. Ectopic expression of the mycobacterial virulence factor ESAT-6 in macrophages led to cofilin1 downregulation. ESAT-6 also increased F-actin, altered cell morphology and impaired phagosome acidification in infections with avirulent <em>M. tuberculosis</em> strain. As cofilin1 is positively regulated by reactive oxygen species (ROS), we examined the role of methionine in ESAT-6-mediated ROS suppression. Mutation of methionine 93 in ESAT-6 increased intracellular ROS, enhanced phagosome acidification, and decreased F-actin levels. These findings reveal that <em>M. tuberculosis</em> impairs phagosome acidification by modulating host actin dynamics at least partially through ESAT-6–mediated suppression of cofilin1 and ROS. Enhancing cofilin1 activity may represent a potential therapeutic strategy to restore phagosome function and improve bacterial clearance, more specifically during the initial establishment of infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102680"},"PeriodicalIF":2.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926761","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

A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle. 新西兰奶牛约翰氏病乳基抗体检测与血清基抗体检测的比较研究。

IF 2.9 3区医学

Tuberculosis Pub Date : 2025-08-27 DOI: 10.1016/j.tube.2025.102679

K M Venkatesh, Nicolas Lopez-Villalobos, Sandeep K Gupta, Garry B Udy, Richard Laven, Shih-Jiuan Chiu, Piyush Bugde, Yoichi Furuya, Venkata Sayoji Rao Dukkipati

{"title":"A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle.","authors":"K M Venkatesh, Nicolas Lopez-Villalobos, Sandeep K Gupta, Garry B Udy, Richard Laven, Shih-Jiuan Chiu, Piyush Bugde, Yoichi Furuya, Venkata Sayoji Rao Dukkipati","doi":"10.1016/j.tube.2025.102679","DOIUrl":"https://doi.org/10.1016/j.tube.2025.102679","url":null,"abstract":"<p><p>Dairy cattle are affected by Johne's disease. It is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Suboptimal diagnostic tests add more to the productivity loss resulting from this disease. Agreement between and within different commercial kits is crucial in the decision-making process of disease surveillance programmes. This study compared two ELISAs, that is, Johne's disease commercial antibody detection kits (A and B), using milk and serum samples from New Zealand dairy cattle. These results were also compared with a subset of faecal PCR results. Five scenarios were considered for the comparison of ELISA tests. The point estimates of kappa coefficients (k) between the serum (0.84-0.94) assays were higher than the milk assays (0.59-0.82). The point estimates of kappa coefficients between serum and milk ELISA outcomes were higher for kit B (k = 0.79-0.86) than for kit A (k = 0.55-0.79). The point estimates of kappa coefficients between the ELISA and faecal PCR outcomes varied between 0.43 and 0.74. ELISA tests had point estimates of sensitivity ranging from 0.67 to 0.88 and specificity from 0.62 to 0.93, relative to the faecal PCR test. Results suggest that serum provides a better choice of sample type when both commercial kits A and B are used for Johne's disease surveillance of dairy cattle in New Zealand. Milk assays can be cost-effective to diagnose MAP-positive animals; kit B can be best suited for New Zealand conditions, provided the repeatability of the results is validated.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":" ","pages":"102679"},"PeriodicalIF":2.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001103","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