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        <title>Frontiers in Tuberculosis | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/tuberculosis</link>
        <description>RSS Feed for Frontiers in Tuberculosis | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-07-08T20:12:14.963+00:00</pubDate>
        <ttl>60</ttl>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1855903</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1855903</link>
        <title><![CDATA[Implementation of sequencing-based surveillance for drug-resistant tuberculosis in Nigeria]]></title>
        <pubdate>2026-07-02T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Heather P. McLaughlin</author><author>Israel Audu</author><author>Monday Tola</author><author>Chika Kingsley Onwuamah</author><author>Julius Ogwu</author><author>Kenneth Atoe</author><author>Chioma Nneka Kunle-Ope</author><author>Isiyaku Ahmadu</author><author>Joshua Gowon</author><author>David B. Meshak</author><author>Mosunmola Iwakun</author><author>Chinedu Ejianya Ude</author><author>Modupe Abiona</author><author>Abidemi Esther Momoh</author><author>Temiloluwa Ore</author><author>Chinenye Angela Ogbu</author><author>Temitope Abigail Abiodun</author><author>Jamie Dawson</author><author>Patricia Hall-Eidson</author><author>Nnaemeka C. Iriemenam</author><author>McPaul Okoye</author><author>Clement Adesigbin</author><author>Obioma Chijioke-Akaniro</author><author>Elom Emeka</author><author>Anyaike Chukwuma</author>
        <description><![CDATA[Sequencing for drug-resistant tuberculosis (DR-TB) surveillance was established in Nigeria for the first time, demonstrating a nationally coordinated referral network for multi-disease sequencing services. Mycobacterium tuberculosis isolates previously identified as resistant to rifampicin and/or isoniazid by genotypic or phenotypic drug susceptibility testing were selected proportionately across all six geopolitical zones in Nigeria. Programmatic use of sequence data for DR-TB surveillance was prioritized, demonstrating additional resistance detection and enhanced monitoring as new TB treatment regimens are scaled up. Sanger sequencing identified resistance to rifampicin and isoniazid missed by drug susceptibility tests routinely used in country, for 11% (5/47) and 2% (1/47) of isolates, respectively. This pilot study demonstrates feasibility and provides an example for programmatic implementation of integrated sequencing, supporting country efforts to strengthen genomic surveillance for DR-TB and improve prevention and control globally.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1830528</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1830528</link>
        <title><![CDATA[The AcasR-FadD9 regulatory axis modulates iron homeostasis and susceptibility to the anti-mycobacterial compound ACA]]></title>
        <pubdate>2026-06-30T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Feng Huang</author><author>Zixin Wang</author><author>Dong Jiang</author><author>Shengyi Li</author><author>Zheng-Guo He</author><author>Hua Zhang</author>
        <description><![CDATA[Mycobacterial drug resistance leads to prolonged treatment, increased mortality, and increased healthcare costs. In this study, 3-azidothiophene-2-carboxylic acid (ACA), a dual-targeting inhibitor of the cell assembly proteins CpsA1 and CpsA2, exerted its activity through an iron-dependent pathway. The screening of drug-resistant mutants revealed that a frameshift mutation in the transcriptional regulator acasR (BCG_0932/Rv0880) conferred ACA resistance. Conversely, acasR overexpression increased bacterial susceptibility. Furthermore, AcasR specifically bound to and repressed the promoter of fadD9 (Rv2590), which was its sole functionally validated target under the tested conditions. Crucially, fadD9 overexpression phenocopied ACA resistance, whereas its deletion heightened susceptibility. Integrated omics and iron assays revealed that ACA induced intracellular iron starvation, a condition exacerbated by fadD9 deletion. These findings reveal a novel resistance pathway in which AcasR modulates mycobacterial drug susceptibility by repressing fadD9, which in turn affects siderophore-mediated iron homeostasis.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1853414</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1853414</link>
        <title><![CDATA[Using interpretable decision trees to explore TB-HIV integration under data constraints: a proof-of-concept analysis]]></title>
        <pubdate>2026-06-25T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ntandazo Dlatu</author><author>Lindiwe Modest Faye</author><author>Mojisola Clara Hosu</author><author>Teke Apalata</author>
        <description><![CDATA[BackgroundStrengthening tuberculosis (TB) and HIV service integration remains a major priority in resource-limited settings, where fragmented care contributes to delayed diagnosis, poor treatment continuity, and suboptimal patient outcomes. Evaluating implementation conditions associated with integrated care remains challenging because health system data are often simplified, inconsistently recorded, and insufficiently structured to capture the complexity of real-world service-delivery processes. This study aimed to demonstrate the application of an interpretable decision-tree framework to explore selected implementation and service-delivery conditions associated with TB-HIV integration using a highly constrained secondary dataset.MethodsA quantitative exploratory proof-of-concept analysis was conducted using a simplified secondary dataset comprising 10 TB-HIV integration implementation cases. Funding, healthcare worker training, patient education, medication access, and infection control were included as binary implementation indicators and entered simultaneously into the decision-tree model. The Gini index was used descriptively to assess node impurity and decision structure. Correlation network analysis was performed to examine patterns of variable alignment, with Pearson correlation coefficients (equivalent to the phi coefficient for binary variables) interpreted solely as descriptive indicators of co-occurrence within the dataset. Given the extremely small sample size and simplified binary structure, all analyses were exploratory and illustrative rather than predictive, inferential, or causal.ResultsFunding emerged as the primary discriminating variable in the decision tree, with all cases reporting increased funding classified as successful (6/6) and all cases without increased funding classified as unsuccessful (4/4). Although all implementation variables were evaluated by the algorithm, no additional variable provided sufficient information gain to generate further branching. Descriptive correlation analysis indicated alignment between funding and TB-HIV integration outcomes (r = 0.78), healthcare worker training (r = 0.76), patient education (r = 0.62), and infection control (r = 0.58). These coefficients are presented solely as descriptive indicators of variable alignment and should not be interpreted as measures of effect size, association strength, or statistical evidence.ConclusionThis proof-of-concept study demonstrates how interpretable decision-tree approaches can be used to explore implementation conditions associated with TB-HIV integration under severe data constraints. The findings do not identify determinants of integration success but rather illustrate how selected implementation conditions were structured within a constrained analytical framework. The study highlights both the utility and limitations of interpretable analytical approaches when applied to small, dichotomized health systems datasets. Future research should employ larger, more granular, process-sensitive, and contextually rich datasets to support robust evaluation of TB-HIV integration in real-world settings.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1854329</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1854329</link>
        <title><![CDATA[Identification of novel DNA gyrase B inhibitors in Mycobacterium species using integrated computational approaches]]></title>
        <pubdate>2026-06-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jagritee Yadav</author><author> Lalhmangaihzuali</author><author>Harish Shukla</author><author>Anshuman Chandra</author><author>Sudhir Kumar Singh</author><author>Meenakshi Singh</author>
        <description><![CDATA[IntroductionDrug-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.MethodsA 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.ResultsApproximately 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.DiscussionCompounds 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1781507</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1781507</link>
        <title><![CDATA[Differential roles of resident lung macrophages during control of murine alveolar and airway Mycobacterium abscessus infection]]></title>
        <pubdate>2026-06-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Kelsey C. Haist</author><author>Jack H. Congel</author><author>Jodi M. Corley</author><author>Alma E. Ochoa</author><author>Jazalle McClendon</author><author>Patrick S. Hume</author><author>Jerry A. Nick</author><author>William J. Janssen</author><author>Kenneth C. Malcolm</author><author>Katherine B. Hisert</author>
        <description><![CDATA[IntroductionMycobacterium abscessus (Mabsc), 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, Mabsc 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 Mabsc infection in healthy lungs remain relevant when Mabsc infection occurs in obstructed airways, rather than in the alveoli, as occurs in bronchiectasis.MethodsUsing an agar bead model of Mabsc infection that prolongs murine small airway infection, replicates factors associated with bronchiectasis, and mirrors pathology of human Mabsc lung disease, we tested the hypothesis that Mabsc infection in obstructed airways elicits a qualitatively different immune response that alveolar Mabsc 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.ResultsDuring the first 2 weeks of the bead model of Mabsc infection, absolute abundance of neutrophils in the lungs was significantly higher and relative abundance of recruited macrophages was lower than in the alveolar Mabsc 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 Mabsc infection, clodronate liposomes were administered oropharyngeally to deplete RAMs. RAMs were essential for early control of alveolar Mabsc infection, but depletion of RAMs had no effect on control of Mabsc burden during bead infection.ConclusionsThese studies demonstrate that murine Mabsc airway infection induced by obstructing small airways with Mabsc embedded in agar beads generates an immune milieu distinct from that induced by Mabsc infection in alveoli, altering the importance of different macrophage populations for control of infection.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1855780</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1855780</link>
        <title><![CDATA[Genomic characterization of drug-resistant Mycobacterium tuberculosis complex in western Kenya reveals predominance of isoniazid resistance and discordance with routine susceptibility testing]]></title>
        <pubdate>2026-06-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Susan Musau</author><author>Susan Odera</author><author>Victor Moses Musyoki</author><author>Eleanor I. Lamont</author><author>Noel Onyango</author><author>Bob Morrison</author><author>Wilfred Murithi</author><author>Steve Wandiga</author><author>Videlis Nduba</author><author>David Sherman</author><author>Marianne W. Mureithi</author>
        <description><![CDATA[IntroductionWhole-genome sequencing (WGS) data on resistance patterns in western Kenya remain limited. We evaluated resistant patterns of Mycobacterium tuberculosis complex (MTBC) isolates from western Kenya based on routine line probe assay (LPA) and/or phenotypic drug-susceptibility testing (DST) using targeted WGS.MethodsIn 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.ResultsOut 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 rpoB (S450L), while isoniazid resistance was dominated by katG S315 T and inhA 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 (p = 0.026); approximately 86% of discordant isolates carrying mutations of uncertain significance.ConclusionWestern 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1797268</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1797268</link>
        <title><![CDATA[Sigma factor M induces an ESX-4-focused regulon in Mycobacterium abscessus]]></title>
        <pubdate>2026-06-05T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jill G. Canestrari</author><author>Shawn Gianola</author><author>Keith M. Derbyshire</author><author>Todd A. Gray</author>
        <description><![CDATA[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 Mycobacterium abscessus where it has been shown to support survival in phagosomes. ESX-4 and putative effector genes in Mycobacterium tuberculosis and Mycobacterium smegmatis are co-induced by a conserved sigma factor, SigM. Identifying the activities conferred by ESX-4 in promoting M. abscessus survival begins with identifying potential secreted substrates. We hypothesized that, in M. abscessus, SigM co-regulates the expression of genes encoding ESX-4 components and secreted effector proteins. We generated a precise deletion of the sigM-rsmA 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 M. abscessus. 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 esx4 locus promoters in M. smegmatis, only the promoter encoding the primary EsxU/EsxT secreted substrates are direct targets in M. abscessus, 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 M. abscessus infection models.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1740382</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1740382</link>
        <title><![CDATA[Non-tuberculous mycobacteria pulmonary disease in Texas: an analysis of 8 years of hospital discharge data]]></title>
        <pubdate>2026-05-29T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Alex Baham</author><author>Jotam G. Pasipanodya</author><author>Devanshi Mehta</author><author>Susan McBride</author><author>Shashikant Srivastava</author>
        <description><![CDATA[BackgroundNon-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.MethodsWe 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.ResultsOut 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.ConclusionsBased 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1805962</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1805962</link>
        <title><![CDATA[Research overview—2025: integrating scientific progress to accelerate global tuberculosis elimination]]></title>
        <pubdate>2026-05-26T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Patrick K. Moonan</author><author>Timothy H. Holtz</author>
        <description><![CDATA[Major scientific advances across the tuberculosis research continuum emerged in 2025, offering new opportunities to accelerate progress toward global elimination. This review synthesizes developments in diagnosis, treatment, prevention, and post-disease care, highlighting innovations that broaden access, strengthen mechanistic insight, and expand the scope of actionable tools. Diagnostic progress included artificial intelligence–enabled chest imaging, noninvasive molecular testing using tongue and stool samples, simple stool-based procedures suitable for decentralized settings, biomarkers that support treatment monitoring, low-complexity nucleic acid tests for extrapulmonary disease, and new point-of-care methods for detecting infection. Culture-free sequencing approaches further improved rapid identification of drug resistance. Therapeutic advances featured shorter all-oral regimens for drug-susceptible and rifampin-resistant disease, along with emerging compounds that target essential microbial pathways. Additional progress in host-directed therapies, vaccines, and nanoparticle-based drug delivery broadened preventive and therapeutic options. Conceptual developments challenged the validity of symptom-based disease categories and supported biologically grounded terminology, while consensus definitions for post-tuberculosis lung disease clarified the substantial long-term respiratory burden among survivors. Despite this momentum, health-system limitations and inequitable access continue to constrain real-world impact. Collectively, the scientific advances of 2025 were substantial and outline a clearer mechanistic and programmatic path toward tuberculosis elimination, but their success will depend on effective implementation and integration into routine care.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1809118</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1809118</link>
        <title><![CDATA[Readiness assessment as a strategy, not an afterthought: leveraging implementation science to integrate tuberculosis comorbidity care in Pakistan's health system]]></title>
        <pubdate>2026-04-23T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Saima Aleem</author><author>Zohaib Khan</author><author>Bilal Ahmad Khan</author><author> Zala</author><author>Saima Afaq</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1750007</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1750007</link>
        <title><![CDATA[Evaluation of the performance of promising host transcriptional biosignatures in predicting TB progression during a 1-year prospective cohort study in Indian household contacts]]></title>
        <pubdate>2026-04-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Synne Jenum</author><author>Steffen Hadasch</author><author>Dhanasekaran Sivakumaran</author><author>Christina Skår Saghaug</author><author>Jonas Høgberg</author><author>Kasama Chusang Larsen</author><author>Sumithra Selvan</author><author>Helene Larsen</author><author>Christian Ritz</author><author>Harleen M. S. Grewal</author>
        <description><![CDATA[IntroductionAchieving 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.MethodsNested 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.ResultsOf 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).DiscussionThe 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1783887</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1783887</link>
        <title><![CDATA[Immunometabolic reprogramming of Mycobacterium tuberculosis-responsive memory CD4+ T cell subsets is linked to long-term protective immunity]]></title>
        <pubdate>2026-04-10T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Vaishnavi Kaipilyawar</author><author>Samantha Leong</author><author>Arianne Lovey</author><author>Lorenzzo L. Stringari</author><author>Reynaldo Dietze</author><author>Jerrold J. Ellner</author><author>Rodrigo Ribeiro-Rodrigues</author><author>Padmini Salgame</author>
        <description><![CDATA[IntroductionMemory CD4+ T cells are central to long-term immunity in tuberculosis (TB), yet their functional roles that define their protective capacity remain unclear. Understanding the immune mechanisms that prevent clinical progression from latent TB infection (LTBI) to active TB disease is critical for the development of next-generation vaccines and biomarkers.MethodsWe characterized the transcriptomic, metabolic, and functional programs of Mycobacterium tuberculosis (Mtb) antigen-stimulated peripheral CD4+ T stem cell (T-SCM), central (T-CM), transitional (T-TM), and effector (T-EM) memory subsets from individuals with remote LTBI. We utilized a multi-platform validation strategy that integrated RNA-sequencing data with protein-level metabolic profiling using “Met-Flow” cytometry and functional growth restriction assays to link memory CD4+ T cell differentiation states to immunometabolism and antimycobacterial function. Finally, we evaluated the immunometabolic profiles of memory CD4+ T cell subsets in an independent, longitudinal cohort of Mtb-exposed progressors and non-progressors from Brazil (GSE112104).ResultsWe identified a differentiation gradient associated with distinct immunometabolic states. T-SCM and T-CM subsets exhibited elevated mitochondrial activity and oxidative metabolism (fatty acid oxidation), supporting their proliferative capacity. In contrast, T-TM and T-EM subsets underwent glycolytic reprogramming and engaged the pentose phosphate pathway, which fueled enhanced cytokine production and Mtb growth restriction. Importantly, we observed that non-progressors exhibit fatty acid oxidation-driven, stem/central memory-like signatures, while progressors and active TB cases display elevated exhaustion markers, glycolytic reprogramming and pro-inflammatory profiles aligned with disease progression.ConclusionCollectively, findings from our proof-of-concept study suggest metabolic state as a key axis connecting Mtb antigen-induced memory T cell differentiation, restimulation-induced transcriptional programming, and durability of immune control. The findings provide the basis for future longitudinal studies to examine the dynamic metabolic and functional modulation in Mtb antigen-specific memory T cell subsets from contained infection to disease progression.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1819209</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1819209</link>
        <title><![CDATA[Editorial: Non-tuberculous mycobacteria and bronchiectasis]]></title>
        <pubdate>2026-04-01T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Octavio M. Rivero-Lezcano</author><author>Ramiro López-Medrano</author><author>Jaime Esteban</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1762713</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1762713</link>
        <title><![CDATA[Dose optimization of inhaled tigecycline in humans to overcome inherent adverse events and maximize bacterial clearance using a physiologically-based pharmacokinetic modeling approach]]></title>
        <pubdate>2026-03-26T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Hyunseo Park</author><author>Amarinder Singh</author><author>Ashish Srivastava</author><author>Bhargavi Thalluri</author><author>Christelle J. Mathieu</author><author>Paridhi Gupta</author><author>Camron M. Pearce</author><author>Malik Zohaib Ali</author><author>Ilham M. Alshiraihi</author><author>Sara E. Maloney Norcross</author><author>Anthony J. Hickey</author><author>Mercedes Gonzalez-Juarrero</author><author>Bernd Meibohm</author>
        <description><![CDATA[IntroductionIntrapulmonary delivery of tigecycline has been highlighted as an optimal strategy for enhancing local drug concentrations at the site of infection in the treatment of Mycobacterium abscessus pulmonary infections. Therefore, determining an appropriate inhaled dose is imperative to optimize therapeutic use of tigecycline. In this study, we aimed at establishing a human dose rationale for inhaled tigecycline by leveraging various preclinical experimental datasets through physiologically-based pharmacokinetic (PBPK) modeling.MethodsThe PBPK model developed to predict plasma and target-site exposure of inhaled tigecycline and to relate these exposures to adverse event thresholds was derived from plasma and tissue concentration-time courses of in vivo mouse studies. Following inter-species scaling, the predictive performance of the model was qualified by comparing model-based simulations with experimental data in rats and literature reports in humans, thereby demonstrating its applicability across species. The final human PBPK model was utilized to predict tigecycline exposure in plasma and major organs of interest, thereby establishing the clinical utility of tigecycline inhaled dosing.ResultsUsing model-based simulations, we predicted the longitudinal exposure profiles of tigecycline in the systemic circulation, the epithelial lining fluid (ELF) in the lungs as site of antibacterial activity, and other major organs following inhalation under clinically relevant conditions. Intrapulmonary aerosol dosing using the currently approved intravenous dose of tigecycline was predicted to result in significantly lower plasma exposure compared to the gastrointestinal adverse event threshold reported in the literature (AUC0−24 6.87 mg·h/L). Additionally, simulated steady-state bone concentrations remained below a threshold which has been previously defined as a steady-state trough concentration leading to bone toxicity in rats. For efficacy, intrapulmonary aerosol administration produced markedly higher peak concentrations in ELF than intravenous dosing, and the simulated exposure in ELF exceeded effective exposure levels identified in murine infection models of Mycobacterium abscessus.DiscussionOur findings indicate that compared to conventional intravenous infusion, inhaled tigecycline offers an improved safety margin and enhances bacterial killing. Based on simulations for multiple dosing scenarios in humans, a dose of 135 mg given every third day by intrapulmonary delivery would result in ELF, bone, and plasma exposures that effectively balance efficacy and safety.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1760581</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1760581</link>
        <title><![CDATA[Advanced diagnostic methods for nontuberculous mycobacterial infections]]></title>
        <pubdate>2026-03-25T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Sneha Singh</author><author>Amresh Kumar Singh</author><author>Sushil Kumar</author><author>Nandini Singh</author><author>Ashwini Kumar Mishra</author><author>Aroop Mohanty</author>
        <description><![CDATA[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 Mycobacterium absessus, M. fortuitum, and M. avium complex and M. tuberculosis 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 Mycobacterium 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 (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.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1678039</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1678039</link>
        <title><![CDATA[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]]></title>
        <pubdate>2026-02-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Harriet N. Garlant</author><author>Kalaiarasan Ellappan</author><author>Noyal Mariya Joseph</author><author>Carrie Turner</author><author>Vishnukanth Govindaraj</author><author>Saka Vinod Kumar</author><author>Sanjeev Kumar</author><author>Seshadri Vasan</author><author>Karen E. Kempsell</author>
        <description><![CDATA[BackgroundTuberculosis (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.MethodsTwenty-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) (n = 15) and extrapulmonary TB (EPTB) (n = 15) patients and high-incidence controls (n = 15). The diagnostic performance of biomarkers, prior signatures, and novel promising combinations were assessed against WHO TPPs for triage and confirmatory tests.ResultsSeveral biomarker signatures successfully distinguished active TB ((ATB) PTB and EPTB combined) from controls. The minimal INDUK signature (GBP1 + IFIT3) 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).ConclusionThis 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.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1713844</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1713844</link>
        <title><![CDATA[An integrated psycho-social intervention to improve self-efficacy toward TB treatment uptake and infection prevention among patients and family caregivers: a multicentric implementation research study protocol]]></title>
        <pubdate>2026-02-13T00:00:00Z</pubdate>
        <category>Study Protocol</category>
        <author>Karikalan Nagaraj</author><author>Bella Devaleenal Daniel</author><author>Chandra Suresh</author><author>Dhanalakshmi Angamuthu</author><author>Shobana Palanisamy</author><author>Muniyandi Malaisamy</author>
        <description><![CDATA[BackgroundThe individuals with tuberculosis (TB) experience a variety of barriers, needs, and challenges when receiving the treatment. Evidence on holistic patient-centered psychosocial interventions that promote self-efficacy and the ability to complete treatment-related tasks and goals is scarce in India.ObjectivesTo adapt an intervention aimed at strengthening the self-efficacy of individuals on TB treatment and their family caregivers, and to evaluate its effectiveness compared with the standard of care on the primary outcome of improved TB treatment self-efficacy and secondary outcomes of improved medication adherence, reduced TB-related stigma, and improved infection control practices.MethodsA multicentric hybrid Type I mixed method implementation research design will be used to adapt and evaluate the implementation feasibility and effectiveness of delivering a self-efficacy-based intervention under National Tuberculosis Elimination Program (NTEP) settings in India. A two-arm non-randomized cluster intervention design will be employed to evaluate the impact of a self-efficacy intervention, which includes individual counseling and peer group sessions (n = 240) in comparison to the standard of care (n = 240) on primary and secondary outcomes. Qualitative in-depth interviews and focus group discussions, guided by the Consolidated Framework for Implementation Research (CFIR), will be conducted to explore contextual factors influencing implementation.DiscussionThe proposed study could generate evidence for a holistic and evidence-informed psycho-social intervention for individuals with TB and their family caregivers. It aims to improve their self-efficacy in overcoming TB treatment challenges and address the key psycho-social barriers comprehensively. Qualitative insights from the study are expected to guide/facilitate the pragmatic scale-up of self-efficacy-based interventions under the National TB program of India.Clinical trial registrationThe study has been registered in the Clinical Trial Registry of India CTRI/2024/05/066847.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1726647</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1726647</link>
        <title><![CDATA[Acceptability and feasibility of oral swabs for tuberculosis diagnosis in young children: a qualitative study from Uganda and Peru]]></title>
        <pubdate>2026-02-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Francesca W. Basile</author><author>Rodrigo Calderón-Flores</author><author>Franziska Held</author><author>Luisa Pollmeier</author><author>Emmanuel Nasinghe</author><author>Godfrey Bagenda</author><author>Lazaaro Mujumbusi</author><author>Rose Namaganda</author><author>Angel Kanyange</author><author>Prossy Mbekeeka</author><author>Abner Tagoola</author><author>Jerrold J. Ellner</author><author>Susan E. Dorman</author><author>Moses Joloba</author><author>Carlos Zamudio</author><author>Adeodata Kekitiinwa</author><author>Rinn Song</author><author>Nora Engel</author>
        <description><![CDATA[BackgroundTuberculosis (TB) remains a leading cause of morbidity and mortality in young children, particularly in settings with limited diagnostic capacity. Oral swabs represent a promising alternative specimen type due to their ease of collection, but evidence regarding their acceptability and feasibility remains limited.MethodsThis qualitative sub-study was nested within the NOD-pedFEND diagnostic trial evaluating novel tests for pediatric TB. We conducted semi-structured interviews and focus group discussions with 81 participants across Uganda (n = 57) and Peru (n = 24), including caregivers (Uganda, n = 30; Peru, n = 7), healthcare workers (Uganda, n = 23; Peru, n = 12), and National TB Program stakeholders (Uganda, n = 4; Peru, n = 5). Participants were recruited purposively from among those involved in or linked to the parent NOD-pedFEND study. Data were analyzed using thematic analysis.ResultsOral swabs were widely perceived as acceptable due to their non-invasive nature, minimal discomfort, and ease of collection. Caregivers and healthcare workers valued the reduced burden on children compared to more invasive sampling methods. Across both countries, participants expressed concerns about perceived low diagnostic sensitivity in children, particularly when compared with reference standard specimens. Despite these reservations, oral swabs were welcomed as a complementary, rather than substitute, diagnostic modality. Stakeholders highlighted their potential role within future point-of-care diagnostic strategies in low-resource settings.ConclusionsOral swabs are acceptable and feasible for pediatric TB diagnosis in diverse settings, though concerns about sensitivity persist. Their integration as an add-on test could expand diagnostic access, especially if incorporated into scalable, point-of-care approaches.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1746664</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1746664</link>
        <title><![CDATA[The “yeast-drop” treatment protocol in the Drosophila model for rapid and cost-effective TB drug testing]]></title>
        <pubdate>2026-01-27T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Maria Vidal</author><author>Esther Fuentes</author><author>Nerea Escobar</author><author>Marta Arch</author><author>Pere-Joan Cardona</author>
        <description><![CDATA[BackgroundPulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading infectious disease globally. The lengthy treatment regimen and the potential side effects increase the probability of relapse and of developing drug resistance. These factors highlight the need for new therapeutic strategies, including host-directed therapies and anti-virulence approaches. However, the drug discovery pipeline is often limited by the simplicity of in vitro models and the cost and scalability challenges of mammalian in vivo models. In this study, we developed a cost-effective administration method using the Drosophila melanogaster–Mycobacterium marinum infection model called “yeast-drop”. This approach facilitates oral delivery and reduces the quantity of compound currently needed for treatment in the fly model.MethodsWe compared the yeast-drop methodology with the standard method commonly used in Drosophila studies. Additionally, we assessed the efficacy of benchmarking antibiotics, host-directed therapies (HDTs), and anti-virulence compounds for TB treatment by measuring fly survival and bacterial burden.ResultsFlies treated with the “yeast-drop” method showed a significant improvement in survival probability and a reduction in colony-forming units (CFUs) compared to non-treated flies. This was comparable to the results achieved with the standard feeding method. Among the compounds tested, linezolid proved to be the most effective antibiotic. HDTs such as aspirin, metformin, and simvastatin also enhanced survival rates and reduced CFUs following treatment, demonstrating conserved immune and metabolic mechanisms between flies and mammals. Similarly, BBH7 and ethoxzolamide, which act as anti-virulence agents, further reinforce the translational value of this type of treatment in the Drosophila model.ConclusionOverall, the Drosophila–M. marinum model, combined with the yeast-drop methodology, offers a reliable, low-cost, and biologically relevant platform for early-stage screening of antimycobacterial, host-directed, and anti-virulence compounds, effectively bridging the gap between in vitro systems and mammalian models.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1718997</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1718997</link>
        <title><![CDATA[Evaluation of a short, all oral treatment regimen including bedaquiline, delamanid, linezolid, clofazimine, and pyrazinamide named “Regimen C” for pre-XDR tuberculosis in Niger]]></title>
        <pubdate>2026-01-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Soumana Boubacar Soumana</author><author>Abdourahamane Yacouba</author><author>Cheikh Aboubacar Abdoul Lawi</author><author>Ibrahim Oumar</author><author>Bassirou Souleymane</author><author>Alphazazi Soumana</author><author>Tapha Ounoussa</author><author>Mahamadou Doutchi</author><author>Mamane Daou</author><author>Souleymane Brah</author><author>Eric Adehossi</author><author>Saidou Mamadou</author>
        <description><![CDATA[BackgroundThe emergence of extensively drug-resistant tuberculosis (XDR-TB) poses a serious challenge to global tuberculosis control, particularly in high-burden countries like Niger. In 2021, a new fully oral, shorter treatment regimen, named regimen C, was adopted nationally.AimThis study aimed to assess its effectiveness under programmatic conditions.MethodsThis was a retrospective, cross-sectional study conducted from April 2021 to December 2024. All patients with pre-XDR and XDR-TB treated in one of the four multidrug-resistant (MDR) TB units in Niger, who received the new standardized regimen and completed their treatment, were included in the study.ResultsA total of 16 patients with pre-XDR-TB were included in the study. Clinical, microbiological, and radiological data were collected. The median age was 30.5 [interquartile range (IQR) 25–39 years], and 62.5% of patients were male. All patients had pulmonary pre-XDR TB. At the end of treatment, a therapeutic success rate of 75.0% was observed. Adverse events occurred in 88.0% of patients, including 2 cases (14.3%) of grade 4 adverse reactions. Undernourished patients tended to have an increased risk of unfavorable treatment outcomes, although this association was not statistically significant (p = 0.18).ConclusionThese findings suggest that the regimen evaluated in this study appears to be effective for the management of pre-XDR tuberculosis in Niger, with a promising treatment success rate.]]></description>
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