Frontiers in tuberculosis最新文献

{"title":"Identification of novel DNA gyrase B inhibitors in <i>Mycobacterium species</i> using integrated computational approaches.","authors":"Jagritee Yadav, Lalhmangaihzuali, Harish Shukla, Anshuman Chandra, Sudhir Kumar Singh, Meenakshi Singh","doi":"10.3389/ftubr.2026.1854329","DOIUrl":"10.3389/ftubr.2026.1854329","url":null,"abstract":"<p><strong>Introduction: </strong>Drug-resistant Mycobacterium tuberculosis remains a major global health challenge, particularly due to the emergence of multidrug-resistant and extensively drug-resistant strains. DNA gyrase, specifically the ATPase domain of GyrB, represents a promising target for the development of novel anti-tubercular agents.</p><p><strong>Methods: </strong>A comprehensive computational workflow was employed, including pharmacophore-based virtual screening of approximately 1,000,000 compounds from the PubChem, ZINC, ChEMBL, and MolPort databases. Hits were filtered using Lipinski's rule of five, structural diversity analysis, molecular docking, ADMET and toxicity assessment, molecular dynamics simulations, and density functional theory analyses.</p><p><strong>Results: </strong>Approximately 30,000 preliminary hits were obtained, which were reduced to 21 candidate molecules and subsequently to 10 unique compounds. Molecular docking identified two lead compounds, D (PubChem ID: 166484985) and I (PubChem ID: 166484904), with strong binding affinity toward the GyrB ATPase domain. ADMET and toxicity analyses indicated favorable drug-likeness and safety profiles. Molecular dynamics simulations and density functional theory studies further confirmed stable protein-ligand interactions and significant electronic reactivity.</p><p><strong>Discussion: </strong>Compounds D and I demonstrated promising ATP-competitive inhibition of the GyrB ATPase domain and exhibited distinct species-specific interaction profiles. These findings support their potential as novel anti-tubercular lead scaffolds for further experimental validation and therapeutic development.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1854329"},"PeriodicalIF":0.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential roles of resident lung macrophages during control of murine alveolar and airway <i>Mycobacterium abscessus</i> infection.","authors":"Kelsey C Haist, Jack H Congel, Jodi M Corley, Alma E Ochoa, Jazalle McClendon, Patrick S Hume, Jerry A Nick, William J Janssen, Kenneth C Malcolm, Katherine B Hisert","doi":"10.3389/ftubr.2026.1781507","DOIUrl":"10.3389/ftubr.2026.1781507","url":null,"abstract":"<p><strong>Introduction: </strong><i>Mycobacterium abscessus</i> (<i>Mabsc</i>), a nontuberculous mycobacterium (NTM), is readily cleared from healthy lungs but can cause infections in immunocompromised individuals and individuals with chronic airways diseases that disrupt mucociliary clearance, such as cystic fibrosis and bronchiectasis. In bronchiectatic airways, <i>Mabsc</i> can persist despite robust immune cell recruitment, raising the possibility that, in addition to impaired mucociliary clearance, local pulmonary immune defects contribute to NTM susceptibility. Since chronic infections result from failed eradication of acute infection, we sought to determine whether immune cell responses critical for control of acute <i>Mabsc</i> infection in healthy lungs remain relevant when <i>Mabsc</i> infection occurs in obstructed airways, rather than in the alveoli, as occurs in bronchiectasis.</p><p><strong>Methods: </strong>Using an agar bead model of <i>Mabsc</i> infection that prolongs murine small airway infection, replicates factors associated with bronchiectasis, and mirrors pathology of human <i>Mabsc</i> lung disease, we tested the hypothesis that <i>Mabsc</i> infection in obstructed airways elicits a qualitatively different immune response that alveolar <i>Mabsc</i> infection. We compared myeloid cell responses in in the two infection models using flow cytometric analyses of lung cells, immunofluorescent imaging, and histopathologic evaluation of lung sections.</p><p><strong>Results: </strong>During the first 2 weeks of the bead model of <i>Mabsc</i> infection, absolute abundance of neutrophils in the lungs was significantly higher and relative abundance of recruited macrophages was lower than in the alveolar <i>Mabsc</i> infection model. Additionally, most resident alveolar macrophages (CD11c⁺ RAMs) in the bead model upregulated CD11b, a marker of inflammation, by 1-week post-infection and maintained high levels of CD11b expression at 3 weeks post infection despite infection occurring in airways, not alveoli. To understand the role of macrophage subsets in controlling <i>Mabsc</i> infection, clodronate liposomes were administered oropharyngeally to deplete RAMs. RAMs were essential for early control of alveolar <i>Mabsc</i> infection, but depletion of RAMs had no effect on control of <i>Mabsc</i> burden during bead infection.</p><p><strong>Conclusions: </strong>These studies demonstrate that murine <i>Mabsc</i> airway infection induced by obstructing small airways with <i>Mabsc</i> embedded in agar beads generates an immune milieu distinct from that induced by <i>Mabsc</i> infection in alveoli, altering the importance of different macrophage populations for control of infection.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1781507"},"PeriodicalIF":0.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization of drug-resistant <i>Mycobacterium tuberculosis</i> complex in western Kenya reveals predominance of isoniazid resistance and discordance with routine susceptibility testing.","authors":"Susan Musau, Susan Odera, Victor Moses Musyoki, Eleanor I Lamont, Noel Onyango, Bob Morrison, Wilfred Murithi, Steve Wandiga, Videlis Nduba, David Sherman, Marianne W Mureithi","doi":"10.3389/ftubr.2026.1855780","DOIUrl":"10.3389/ftubr.2026.1855780","url":null,"abstract":"<p><strong>Introduction: </strong>Whole-genome sequencing (WGS) data on resistance patterns in western Kenya remain limited. We evaluated resistant patterns of <i>Mycobacterium tuberculosis</i> complex (MTBC) isolates from western Kenya based on routine line probe assay (LPA) and/or phenotypic drug-susceptibility testing (DST) using targeted WGS.</p><p><strong>Methods: </strong>In this cross-sectional study, 1,053 archived MTBC isolates from 12 counties in western Kenya were analyzed. An enriched subset of 316 isolates was selected for WGS, of which 290 produced high-quality genomes. Genomic data were analyzed to determine lineage distribution and identify drug resistance mutations using WHO mutation catalogue.</p><p><strong>Results: </strong>Out of the 1,053 isolates, 127 (12%) showed resistance to at least one anti-TB drug. Isoniazid resistant-rifampicin susceptible (Hr-TB) isolates were the most common (52; 40%), followed by rifampicin-resistant (33;26%) and multidrug-resistant (23;18%). The predominance of Hr-TB is consistent with reports from Kenya and other high-burden settings. Enriched WGS subset identified resistance-associated mutations in 43/290 (14%) isolates, with similar resistance patterns. Rifampicin resistance was mainly associated with <i>rpoB</i> (S450L), while isoniazid resistance was dominated by <i>katG</i> S315 T and <i>inhA</i> promoter mutations. Resistant isolates were mainly concentrated in Kisii, Migori, Homa Bay, and Siaya, predominantly within Lineages 4 and 3. Discordance was observed between routine testing and WGS (<i>p</i> = 0.026); approximately 86% of discordant isolates carrying mutations of uncertain significance.</p><p><strong>Conclusion: </strong>Western Kenya shows geographic DR-TB heterogeneity with predominant Hr-TB, which rifampicin-based diagnostics risk under-detection. Despite observed discordance, Integrating WGS with routine testing will strengthen surveillance, improve isoniazid resistance detection, and support appropriate treatment management in high-burden settings.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1855780"},"PeriodicalIF":0.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sigma factor M induces an ESX-4-focused regulon in <i>Mycobacterium abscessus</i>.","authors":"Jill G Canestrari, Shawn Gianola, Keith M Derbyshire, Todd A Gray","doi":"10.3389/ftubr.2026.1797268","DOIUrl":"10.3389/ftubr.2026.1797268","url":null,"abstract":"<p><p>Mycobacteria encode as many as five distinct Type VII (ESX) secretion systems that function in nutrient acquisition, cell-cell interaction, membrane integrity and pathogenesis. The biological activities of ESX systems are determined by the effector proteins they secrete. ESX-4 is the ancestral secretion system and is conserved throughout mycobacteria, including <i>Mycobacterium abscessus</i> where it has been shown to support survival in phagosomes. ESX-4 and putative effector genes in <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium smegmatis</i> are co-induced by a conserved sigma factor, SigM. Identifying the activities conferred by ESX-4 in promoting <i>M. abscessus</i> survival begins with identifying potential secreted substrates. We hypothesized that, in <i>M. abscessus</i>, SigM co-regulates the expression of genes encoding ESX-4 components and secreted effector proteins. We generated a precise deletion of the <i>sigM</i>-<i>rsmA</i> locus, encoding SigM and its dedicated anti-sigma factor. Performing RNA-seq using this deletion strain and a SigM-expressing complementation derivative, we identified SigM-responsive mRNAs in <i>M. abscessus</i>. Analysis of responsive promoters defined a consensus SigM-binding site, indicating direct induction by SigM. Together these data defined 15 SigM-targeted loci transcribing 50 genes with annotations and structures consistent with ESX secretion. While SigM induces multiple <i>esx4</i> locus promoters in <i>M. smegmatis</i>, only the promoter encoding the primary EsxU/EsxT secreted substrates are direct targets in <i>M. abscessus</i>, suggesting that production of the secretion apparatus is controlled by other transcription factors. The putative effector complexes identified here present strong candidates for the pathogenic roles previously reported for ESX-4 in <i>M. abscessus</i> infection models.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1797268"},"PeriodicalIF":0.0,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-tuberculous mycobacteria pulmonary disease in Texas: an analysis of 8 years of hospital discharge data.","authors":"Alex Baham, Jotam G Pasipanodya, Devanshi Mehta, Susan McBride, Shashikant Srivastava","doi":"10.3389/ftubr.2026.1740382","DOIUrl":"10.3389/ftubr.2026.1740382","url":null,"abstract":"<p><strong>Background: </strong>Non-tuberculous mycobacterial (NTM) pulmonary disease (PD) is a recognized chronic condition associated with high healthcare utilization. Texas statewide NTM diagnosis-coded inpatient discharges per 100,000 discharge records (healthcare utilization) have not been systematically studied.</p><p><strong>Methods: </strong>We analyzed Texas hospital inpatient discharge public use data between 2016 and 2023 for all 254 Texas counties. MS-EXCEL and SPSS were used for data collection and analysis.</p><p><strong>Results: </strong>Out of 23.33 million hospital discharge records, 12,587 were identified to have an NTM diagnosis-coded inpatient discharge. Among the patients with NTM, 3.3% of the patients were aged 0-17 years, 19.5% were 18-44 years, 29.5% were 45-64 years, and 47.7% were 65 + years old. The NTM diagnosis-coded inpatient discharge rate in Texas was calculated to be 59.9/100,000 records (range 46.1-62.6). A total of 815 NTM cases were reported in Northeast Texas and 4,203 cases in the Gulf Coast counties. The total number of in-hospital deaths among the NTM-coded discharges was 692 (5.5% of total NTM cases). The number of patients with NTM covered under Medicare Part A was 5,102 and 1,521 were on Medicaid.</p><p><strong>Conclusions: </strong>Based on the hospital discharge data analysis, there appears to be regional variation in the prevalence of NTM disease in Texas. Further studies are needed to determine these variations and to improve our understanding of NTM-PD in Texas.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1740382"},"PeriodicalIF":0.0,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Readiness assessment as a strategy, not an afterthought: leveraging implementation science to integrate tuberculosis comorbidity care in Pakistan's health system.","authors":"Saima Aleem, Zohaib Khan, Bilal Ahmad Khan, Zala, Saima Afaq","doi":"10.3389/ftubr.2026.1809118","DOIUrl":"10.3389/ftubr.2026.1809118","url":null,"abstract":"<p><p>Health facility readiness assessment is a foundational element in designing and implementing integrated tuberculosis (TB) and comorbidity interventions, particularly in low- and middle-income countries (LMICs) like Pakistan. The integration of TB care with management of comorbid conditions like diabetes mellitus, depression, and tobacco use is complicated and challenged by diverse, multifaceted barriers at the health system, organizational, and individual levels. Evidence-based frameworks, such as Consolidated Framework for Implementation Research (CFIR), Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, and related tools, help researchers to systematically evaluate service system capacity for service delivery, determine operational gaps and shortcomings, and understand socio-cultural and infrastructural constraints. This ensures that subsequent interventions are not only scientifically grounded but also tailored and well-suited to local capacities, thereby enhancing the sustainability and overall effectiveness of integration. In this perspective paper, we argue that readiness assessment should be institutionalized that is, formally embedded within service delivery structure, routine policy, planning, and decision-making processes, as a strategic prerequisite for integrating tuberculosis and comorbidity care, and we highlight how implementation science frameworks can support context-sensitive planning and scale-up in Pakistan and other similar health system settings.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1809118"},"PeriodicalIF":0.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the performance of promising host transcriptional biosignatures in predicting TB progression during a 1-year prospective cohort study in Indian household contacts.","authors":"Synne Jenum, Steffen Hadasch, Dhanasekaran Sivakumaran, Christina Skår Saghaug, Jonas Høgberg, Kasama Chusang Larsen, Sumithra Selvan, Helene Larsen, Christian Ritz, Harleen M S Grewal","doi":"10.3389/ftubr.2026.1750007","DOIUrl":"10.3389/ftubr.2026.1750007","url":null,"abstract":"<p><strong>Introduction: </strong>Achieving the goal of the End TB Strategy depends on new tools, preferably blood-based point-of-care (POC) tests, to identify individuals at risk of progression from M. tuberculosis infection to subclinical or clinical tuberculosis (TB). A decade of signature discovery and validation has resulted in several transcriptional signatures with promising capacity for predicting TB progression within the next 3-6 months, but evaluation of signature performance in Asian populations is lacking.</p><p><strong>Methods: </strong>Nested within a prospective observational cohort study of Indian household contacts (HHC study), we adapted the RISK6 and Sweeney3 along with our locally derived INDIA11 signature to the microfluidic RT-qPCR platform (Fluidigm) and evaluated their capacity to predict TB progression during a 12-month follow-up in a head-to-head comparison. As readily available in our dataset, the recently published single-gene signatures GBP2, FCGR1B, and SERPING1 were also assessed.</p><p><strong>Results: </strong>Of the 525 recruited household contacts, 12 (6 cases in children aged 5-14 years) progressed to TB (5 at 6 months, 7 at 12 months) as defined by growth of M. tuberculosis in respiratory specimens. RISK6 and Sweeney3 were successfully adapted to the Fluidigm platform. One gene in the INDIA11 assay failed, resulting in the INDIA10 signature with an overall failure rate of 5.7%. RISK6, Sweeney3, and INDIA10 demonstrated comparable but statistically non-significant predictive performance for TB progression, with AUCs: RISK6 0.61 (95%CI 0.41-0.82), Sweeney3 0.61 (95%CI 0.41-0.80), INDIA10 0.59 (95%CI 0.46-0.72). Applying a fixed value of sensitivity 75% corresponding to the WHO minimum target for TB prediction resulted in the corresponding specificities RISK6 0.49 (95%CI 0.41-0.56), Sweeney3 0.32 (95%CI 0.25-0.39), and INDIA10 0.42 (95%CI 0.35-0.50). Of single-gene signatures, the AUCs of FCGR1B and GBP2 were significant with specificities of FCGR1B 0.56 (95%CL 0.49-0.64) and GBP 0.50 (95%CL 0.43-0.58).</p><p><strong>Discussion: </strong>The expression of interferon-gamma-inducible gene signatures were able to discriminate between TB progressors and non-progressors in an hitherto underexplored Indian population, supporting the generalizability of RNA technology to this setting. Given the limited sensitivity and specificity of current biosignatures in all populations, exploration of integrated diagnostic algorithms relying on established and novel tools in a multidisciplinary approach is warranted.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1750007"},"PeriodicalIF":0.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Non-tuberculous mycobacteria and bronchiectasis.","authors":"Octavio M Rivero-Lezcano, Ramiro López-Medrano, Jaime Esteban","doi":"10.3389/ftubr.2026.1819209","DOIUrl":"10.3389/ftubr.2026.1819209","url":null,"abstract":"","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1819209"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced diagnostic methods for nontuberculous mycobacterial infections.","authors":"Sneha Singh, Amresh Kumar Singh, Sushil Kumar, Nandini Singh, Ashwini Kumar Mishra, Aroop Mohanty","doi":"10.3389/ftubr.2026.1760581","DOIUrl":"10.3389/ftubr.2026.1760581","url":null,"abstract":"<p><p>Nontuberculous mycobacteria (NTM) represent an increasingly significant cause of pulmonary and extrapulmonary infections, but are sometimes misinterpreted as tuberculosis (TB) owing to overlapping clinical and microbiological characteristics. Conventional diagnostic approaches, such as Ziehl-Neelsen staining and culture in a Mycobacterial Growth Indicator Tube (MGIT) system, are constrained by extended incubation times, are insufficient for accurate species differentiation, and are limited by prolonged incubation periods. Recent molecular and genomic advances have transformed NTM diagnostics by enabling rapid, specific, and high-resolution identification. Line probe assays (e.g., GenoType Mycobacterium CM/AS assay) and multiplex PCR have enhanced the ability to distinguish between NTM species such as <i>Mycobacterium absessus, M. fortuitum</i>, and <i>M. avium</i> complex and <i>M. tuberculosis</i> complex, which is essential for proper treatment and epidemiological mapping. Among newer proteomic platforms, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has emerged as a transformative, cost-effective technology capable of identifying <i>Mycobacterium</i> species directly from culture isolates through protein fingerprinting. It provides rapid, reproducible, and highly discriminatory identification between closely related species. Next-generation sequencing (NGS) and whole genome sequencing approaches now offer unprecedented insight into species identification, strain typing, and drug-resistance prediction, complementing traditional culture-based susceptibility testing. Newer techniques such as metagenomics NGS (mNGS), targeted NGS (tNGS) multilocus sequence typing, and mycobacterial interspersed repetitive unit-variable number tandem repeats <b>(</b>MIRU-VNTR) genotyping facilitate subspecies-level resolution and real-time outbreak surveillance. Moreover, molecular beacons, insertion sequence analysis, and repetitive sequence-based polymerase chain reaction (Rep-PCR) enhance detection sensitivity even in paucibacillary samples. The integration of genomic data with automated diagnostic system promises earlier intervention, accurate species delineation, and improved patient outcome.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1760581"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of host-immune biomarker signatures as multiplex qPCR diagnostic assays: a pilot study toward meeting WHO target product profiles for TB diagnosis in India.","authors":"Harriet N Garlant, Kalaiarasan Ellappan, Noyal Mariya Joseph, Carrie Turner, Vishnukanth Govindaraj, Saka Vinod Kumar, Sanjeev Kumar, Seshadri Vasan, Karen E Kempsell","doi":"10.3389/ftubr.2025.1678039","DOIUrl":"10.3389/ftubr.2025.1678039","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Current diagnostic tools are limited, especially in low-resource settings. The World Health Organization's (WHO) Target Product Profiles (TPPs) call for rapid, non-sputum-based diagnostics with high sensitivity and specificity. This study evaluates our previously published TB-associated host-immune biomarkers alongside small-size signatures from other studies, in our previously published non-human primate (NHP) TB infection study dataset (GSE76703) and two previously published human datasets (GSE144127, GSE42834), which include other disease group comparators, including sarcoidosis. These were also evaluated in a small-scale, exploratory qPCR pilot study to assess the feasibility of implementing these previously validated signatures in a South Indian TB patient cohort, comparing their diagnostic performance against WHO TPP criteria.</p><p><strong>Methods: </strong>Twenty-six genes from published signatures (INDUK, Roe1/Roe3, Sweeney3, RISK6) were analyzed in these NHP and human datasets, using network and machine learning approaches, prior to exploratory evaluation using single and multiplex qPCR assays. These were tested using peripheral blood sample RNAs from pulmonary TB (PTB) (<i>n</i> = 15) and extrapulmonary TB (EPTB) (<i>n</i> = 15) patients and high-incidence controls (<i>n</i> = 15). The diagnostic performance of biomarkers, prior signatures, and novel promising combinations were assessed against WHO TPPs for triage and confirmatory tests.</p><p><strong>Results: </strong>Several biomarker signatures successfully distinguished active TB ((ATB) PTB and EPTB combined) from controls. The minimal INDUK signature (<i>GBP1</i> + <i>IFIT3</i>) met the optimal TPP criteria for both triage and confirmatory testing for PTB (100% sensitivity and specificity, area under the receiver operating characteristic curve (AUROC:1)) and achieved the 80% sensitivity, 100% specificity threshold for EPTB (AUROC: 0.92 CI: 0.8261-1.00). Combined signatures incorporating genes from INDUK, Roe1, and Sweeney3 further improved diagnostic accuracy for ATB overall (AUROC: 0.98 95% CI: 0.9472-1.00).</p><p><strong>Conclusion: </strong>This preliminary pilot study demonstrates successful evaluation of biomarker signatures as diagnostic qPCR assays for TB diagnosis and, to our knowledge, is the first study to demonstrate the potential for combined host-immune biomarker signatures from different studies that meet WHO TPP benchmarks. These findings support the potential for the development of low-cost, field-adaptable diagnostic tools. Further validation is now under way on a larger cohort of TB patients and controls.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"3 ","pages":"1678039"},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}