This paper develops and analyzes a Caputo fractional-order mathematical model for tuberculosis (TB) transmission that incorporates testing, therapy, isolation, and treatment interventions. The model divides the population into five compartments—susceptible, exposed, infectious, isolated, and recovered—and its qualitative properties, including positivity, boundedness, existence, and uniqueness of solutions, are established. The basic reproduction number R0 is derived, and sensitivity analysis identifies transmission, progression, testing, and treatment rates as critical drivers of TB dynamics. Using the Laplace–Adomian decomposition method (LADM), numerical simulations are performed to assess the impact of fractional-order derivatives on disease spread and control. The results show that increasing the order of the fractional derivative enhances the accuracy of the model and reveals memory effects in TB dynamics. Moreover, early diagnosis, therapy, and isolation significantly reduce infection levels and improve recovery outcomes. These findings highlight the advantages of fractional-order models over classical approaches and provide valuable insights for designing effective TB control strategies.
{"title":"Analysis of tuberculosis infection dynamics using Caputo fractional-order models with diagnosis and treatment interventions","authors":"Oluwafemi Ezekiel Abiodun , Morufu Oyedunsi Olayiwola","doi":"10.1016/j.tube.2025.102694","DOIUrl":"10.1016/j.tube.2025.102694","url":null,"abstract":"<div><div>This paper develops and analyzes a Caputo fractional-order mathematical model for tuberculosis (TB) transmission that incorporates testing, therapy, isolation, and treatment interventions. The model divides the population into five compartments—susceptible, exposed, infectious, isolated, and recovered—and its qualitative properties, including positivity, boundedness, existence, and uniqueness of solutions, are established. The basic reproduction number R<sub>0</sub> is derived, and sensitivity analysis identifies transmission, progression, testing, and treatment rates as critical drivers of TB dynamics. Using the Laplace–Adomian decomposition method (LADM), numerical simulations are performed to assess the impact of fractional-order derivatives on disease spread and control. The results show that increasing the order of the fractional derivative enhances the accuracy of the model and reveals memory effects in TB dynamics. Moreover, early diagnosis, therapy, and isolation significantly reduce infection levels and improve recovery outcomes. These findings highlight the advantages of fractional-order models over classical approaches and provide valuable insights for designing effective TB control strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102694"},"PeriodicalIF":2.9,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259218","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}
Pub Date : 2025-09-19DOI: 10.1016/j.tube.2025.102693
Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang
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 Mycolicibacterium smegmatis (formerly Mycobacterium smegmatis). 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 M. smegmatis proliferation by disrupting amino acid homeostasis and interfering with aerobic respiration.
{"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}
Pub Date : 2025-09-19DOI: 10.1016/j.tube.2025.102692
Natalia Przysucha , Magdalena Paplińska-Goryca , Katarzyna Górska , Paulina Misiukiewicz-Stępień , Michał Mlącki , Agata Cyran , Rafal Krenke
Background
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.
Methods
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.
Results
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.
Conclusion
YKL-40, but not CHIT-1, may contribute to the pleural inflammatory response associated with tuberculosis.
几丁质酶和几丁质酶样蛋白参与肺部疾病的病理生理。本研究旨在评估壳三醇苷酶（CHIT1）和YKL-40在结核性胸腔积液（TPE）中的意义，确定它们的细胞来源，并评估它们作为TPE生物标志物的诊断潜力。方法回顾性观察66例不同来源的胸腔积液：恶性（MPE）、结核性（TPE）、肺副性（PPE）和肺泡性（TE）。测定胸膜液中YKL-40和CHIT1水平。免疫组化染色法检测结核性胸膜肉芽肿组织中YKL-40和CHIT1的表达。结果TPE患者的CHIT1和YKL-40水平中位数最高，分别为70.51（四分位间距[IQR] 49.65 ~ 136.98） ng/mL和569.84 (IQR 530.32 ~ 706.01) ng/mL。TPE中YKL-40含量显著高于PPE （387.98 [IQR 262.94-539.09] ng/mL, p < 0.01）和TE （254.95 [IQR 188.93-334.1] ng/mL, p < 0.001）。TPE中YKL-40水平与巨噬细胞百分比（r = 0.73, p = 0.003）和腺苷脱氨酶活性（r = 0.82, p < 0.001）呈极显著正相关。我们发现YKL-40在结核样胸膜肉芽肿中表达强烈。结论ykl -40可能参与结核相关胸膜炎症反应，而CHIT-1不参与。
{"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}
Pub Date : 2025-09-12DOI: 10.1016/j.tube.2025.102691
Miguel Pinto , Rita Macedo
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.
{"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}
Pub Date : 2025-09-11DOI: 10.1016/j.tube.2025.102690
Thomas R. Ioerger, Anthony Shatby
Multiple studies have reported genes in the M. tuberculosis (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 (resR, phoR). 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.
{"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}
Pub Date : 2025-09-06DOI: 10.1016/j.tube.2025.102689
Vandana Singh , Mohd Mustkim Ansari , Debashis Dutta , R.S. Rajmani , Amit Singh , Bhupendra N. Singh
FadR, a GntR family transcriptional regulator, is known to maintain fatty acid homeostasis in prokaryotes. In this study, a fadR deletion mutant was generated in Mycobacterium bovis, 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 M. bovis and the ΔfadR 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 fadR 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.
{"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}
Pub Date : 2025-09-05DOI: 10.1016/j.tube.2025.102688
Promod K. Mehta, Jefry Sebastian
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), i.e. in-house PCR/multiplex-PCR, commercial real-time PCR (e.g. Cobas TaqMan/LightCycler), line probe assay (e.g. 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 nrdB, while TruPlus targets IS6110+nrdZ for the identification of Mtb within 1 h. After a positive result, an ‘add-on’ chip, i.e. 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, i.e. 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.
{"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}
Pub Date : 2025-09-01DOI: 10.1016/j.tube.2025.102677
Hinpetch Daungsupawong , Viroj Wiwanitkit
{"title":"Correspondence on “Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets”","authors":"Hinpetch Daungsupawong , 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}
Pub Date : 2025-09-01DOI: 10.1016/j.tube.2025.102678
Xutao Wang , Katie Harper , Pranay Sinha , W. Evan Johnson , Prasad Patil
{"title":"Response to “Correspondence on ‘Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets’”","authors":"Xutao Wang , Katie Harper , Pranay Sinha , W. Evan Johnson , 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}
Mycobacterium tuberculosis (M. tuberculosis) persists within macrophages by evading phagosome maturation. In this study, we considered the role of actin dynamics in this process. Macrophages infected with virulent M. tuberculosis 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 M. tuberculosis 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 M. tuberculosis 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.
{"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}
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