Tuberculosis最新文献

{"title":"Exploring CHIT1 and YKL-40 in tuberculous pleural effusion: Insights and implications","authors":"Natalia Przysucha ,&nbsp;Magdalena Paplińska-Goryca ,&nbsp;Katarzyna Górska ,&nbsp;Paulina Misiukiewicz-Stępień ,&nbsp;Michał Mlącki ,&nbsp;Agata Cyran ,&nbsp;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 &lt; 0.01)] and TE (254.95 [IQR 188.93–334.1 ng/ml] ng/mL, p &lt; 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 &lt; 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}

{"title":"Whole-genome sequencing-based surveillance system for Mycobacterium tuberculosis in Portugal","authors":"Miguel Pinto ,&nbsp;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}

{"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,&nbsp;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}

{"title":"M. bovis FadR mutant exhibits an altered colony morphotype and increased virulence","authors":"Vandana Singh ,&nbsp;Mohd Mustkim Ansari ,&nbsp;Debashis Dutta ,&nbsp;R.S. Rajmani ,&nbsp;Amit Singh ,&nbsp;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}

{"title":"Diagnosis of extrapulmonary tuberculosis by Truenat® MTB/MTB Plus assay","authors":"Promod K. Mehta,&nbsp;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}

{"title":"Correspondence on “Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets”","authors":"Hinpetch Daungsupawong ,&nbsp;Viroj Wiwanitkit","doi":"10.1016/j.tube.2025.102677","DOIUrl":"10.1016/j.tube.2025.102677","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102677"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800389","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":"Response to “Correspondence on ‘Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets’”","authors":"Xutao Wang ,&nbsp;Katie Harper ,&nbsp;Pranay Sinha ,&nbsp;W. Evan Johnson ,&nbsp;Prasad Patil","doi":"10.1016/j.tube.2025.102678","DOIUrl":"10.1016/j.tube.2025.102678","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102678"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859669","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":"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 ,&nbsp;R.J. Retnakumar ,&nbsp;K.C. Sivakumar ,&nbsp;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}

{"title":"Biomarkers for diagnosing pulmonary tuberculosis in adolescents: Peripheral blood monocyte myotubularin-related protein 4 and oncostatin M genes","authors":"Yuxia Sha ,&nbsp;Haoquan Zhou ,&nbsp;Bingda Yan ,&nbsp;Xianzong Da ,&nbsp;Meilin Shao ,&nbsp;Ye Li ,&nbsp;Shenggang Ding","doi":"10.1016/j.tube.2025.102676","DOIUrl":"10.1016/j.tube.2025.102676","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/objectives&lt;/h3&gt;&lt;div&gt;Although research has increasingly been focused on pulmonary tuberculosis (PTB) in adolescents, its diagnosis remains complex and challenging. Thus, the use of host transcription markers in the diagnosis of adolescent PTB was evaluated in this study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study cohort comprised 40 adolescents (aged 14–18 years) with PTB who had received their first PTB diagnosis at Anhui Provincial Chest Hospital, China, between January and December 2023 (case group) and 32 healthy adolescents who had undergone physical examinations at The First Affiliated Hospital of the University of Science and Technology of China during the same period (control group). Peripheral blood samples were collected from both groups, and isolated monocytes were subjected to transcriptome sequencing and bioinformatic analysis. The relevant genes were confirmed through quantitative polymerase chain reaction. The diagnostic value of these genes in adolescent PTB patients was analysed using receiver operating characteristic curves. Furthermore, an in vitro model was constructed by infecting THP-1 cells with the &lt;em&gt;Mycobacterium tuberculosis&lt;/em&gt; strain H37Ra to assess whether the in vitro expression levels of the identified genes were consistent with those of the genes in the peripheral blood monocytes of adolescents with PTB. The specific mechanisms were explored using methods such as lentiviral infection, flow cytometry, immunofluorescence, Western blotting, and qRT‒PCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results revealed that the expression level of the &lt;em&gt;myotubularin-related protein 4&lt;/em&gt; gene (&lt;em&gt;MTMR4&lt;/em&gt;) was lower in the case group than in the control group (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001; area under the curve: 0.946; 95 % confidence interval: 0.893–0.999; cut-off value: 0.844; sensitivity: 0.875; specificity: 0.969). The expression level of the &lt;em&gt;oncostatin M&lt;/em&gt; gene (&lt;em&gt;OSM&lt;/em&gt;) was greater in the case group than in the control group (&lt;em&gt;P&lt;/em&gt; = 0.014; area under the curve: 0.962; 95 % confidence interval: 0.914–1.000; cut-off value: 0.919; sensitivity: 0.950; specificity: 0.969). However, no significant between-group difference was detected in the expression level of the complement &lt;em&gt;component 1q subcomponent A&lt;/em&gt; gene. The results from the in vitro experiment indicated that the expression levels of &lt;em&gt;MTMR4&lt;/em&gt; and &lt;em&gt;OSM&lt;/em&gt; were consistent between the H37Ra-infected cells and the case group samples. Bioinformatics analysis revealed that cytokine–cytokine receptor interactions, JAK/STAT signalling and PI3K/cell survival-related pathways play key roles in the pathogenesis of adolescent PTB. Additionally, we found that H37Ra infection affected tuberculosis progression via the OSM/PI3K/GPX4 pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Peripheral blood monocyte &lt;em&gt;OSM&lt;/em&gt; and &lt;em&gt;MTMR4&lt;/em&gt; may serve as biomarkers of adolescent PTB. We speculate that targeting the OSM signallin","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102676"},"PeriodicalIF":2.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809517","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":"Incidence of infectious diseases in children with Mycobacterium tuberculosis in Japan, 2007–2022","authors":"Yuko Hamaguchi ,&nbsp;Takayuki Yamaguchi ,&nbsp;Takashi Yoshiyama","doi":"10.1016/j.tube.2025.102674","DOIUrl":"10.1016/j.tube.2025.102674","url":null,"abstract":"<div><div>The objective of this study was to understand the descriptive epidemiology of childhood tuberculosis (TB) in Japan under the 2013 Bacillus Calmette–Guérin (BCG) immunization program modification. The median percentage of annual vaccination coverage for infants aged &lt;13 months was 97.0 % during follow-up (2007–2022). The age at which most infants received their vaccinations was 3 months before 2013 and 5 months after 2013. During follow-up, the number of childhood TB notifications and annual incidence declined by approximately 60 % and 40 %, respectively. A multivariate-adjusted model analysis was performed by birth year to determine the association between childhood TB and the 2013 BCG immunization program modification. However, childhood TB was associated with age and BCG vaccination history but not with the 2013 BCG immunization program modification. This study represents a valuable resource for future research, elucidating the efficacy of BCG as well as the impact of BCG policies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102674"},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769104","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}