Frontiers in tuberculosis最新文献

{"title":"Translating drug-resistant tuberculosis surveillance into molecular-biophotonic diagnostic innovation in rural Eastern Cape, South Africa.","authors":"Ncomeka Sineke, Kamvelihle Sabisa, Ntandazo Dlatu, Saturnin Ombinda-Lemboumba, Teke Apalata, Lindiwe Modest Faye","doi":"10.3389/ftubr.2026.1937755","DOIUrl":"10.3389/ftubr.2026.1937755","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in South Africa, particularly in rural settings with constrained access to rapid molecular diagnostics. There is a need to identify locally relevant molecular targets that could inform the future development of affordable point-of-care (POC) diagnostic platforms. This study used routine DR-TB surveillance data to develop an epidemiology-guided framework for prioritizing molecular targets for future molecular-biophotonic diagnostic development.</p><p><strong>Methods: </strong>A retrospective secondary analysis was conducted using routine DR-TB programme data from 402 patients managed at two decentralized treatment facilities in the rural Eastern Cape Province, South Africa, between 2020 and 2024. Resistance categories, treatment outcomes, and programme vulnerability indicators were analysed descriptively. A diagnostic prioritization framework integrating disease burden, frequency of resistance categories, treatment outcome vulnerability, programme impact, and potential suitability for decentralized implementation was used to prioritize established resistance-associated molecular targets. Molecular targets were informed by published evidence; no isolate-level mutation analysis, sequencing, biosensor development, or analytical or clinical validation of a diagnostic platform was performed.</p><p><strong>Results: </strong>Rifampicin-resistant tuberculosis (RR-TB) (47.5%) and multidrug-resistant tuberculosis (MDR-TB) (44.3%) accounted for 91.8% of DR-TB cases, while pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) accounted for 5.7% and 2.5%, respectively. Declining treatment success and increasing proportions of unevaluated outcomes among RR-TB and MDR-TB indicated programme vulnerability; however, the available data did not permit causal attribution of these patterns to diagnostic limitations. The framework prioritized <i>rpoB, katG,</i> and <i>inhA</i> as high-priority targets, followed by <i>gyrA, gyrB, rrs,</i> and <i>eis</i> as medium-priority targets, with <i>embB, pncA, Rv0678, atpE,</i> and <i>pepQ</i> identified for future expansion. These targets were conceptually mapped to candidate biophotonic biosensing approaches; their diagnostic performance and POC suitability were not evaluated in this study.</p><p><strong>Conclusions: </strong>This study proposes an epidemiology-guided framework for prioritizing molecular targets for future DR-TB diagnostic development in rural settings. The molecular-biophotonic component is conceptual and does not represent a validated diagnostic technology. Mutation-level characterization, biosensor development, analytical evaluation, and prospective clinical validation are required to determine the performance, feasibility, and potential POC applicability of the proposed approach.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1937755"},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149279571","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":"Spondylodiscitis in a tuberculosis-endemic setting in Somalia: epidemiological, clinical, radiological, and outcome findings from a retrospective study.","authors":"Hussein Salad Yusuf, Abdirisak Ali Abukar, Mohamed Said Adan, Abdiaziz Siad Mohamed, Zakariye Yusuf Mohamed, Mustaf Abdi Ulusow, Mohamed Osman Dahir Alasow, Abdiwahid Ahmed Ibrahim, Naimo Awil Dahir","doi":"10.3389/ftubr.2026.1971442","DOIUrl":"10.3389/ftubr.2026.1971442","url":null,"abstract":"<p><strong>Background: </strong>Spondylodiscitis is an important cause of spinal morbidity in tuberculosis (TB)-endemic settings, where limited microbiological capacity may complicate differentiation of tuberculous from non-tuberculous disease. Data describing the clinical spectrum and outcomes of spondylodiscitis in Somalia are limited.</p><p><strong>Objective: </strong>To describe the demographic, clinical, radiological, microbiological, treatment, and outcome characteristics of patients with spondylodiscitis and to explore factors associated with clinical outcome.</p><p><strong>Methods: </strong>We conducted a retrospective observational study of 121 eligible patients diagnosed with spinal infection at Mogadishu Somali Turkey Recep Tayyip Erdoğan Training and Research Hospital between 1 August 2023 and 31 July 2024. Demographic, clinical, radiological, microbiological, treatment, and outcome data were extracted from routine records. Associations were assessed using chi-square or Fisher's exact tests for categorical variables and Mann-Whitney U or independent-samples t-tests as appropriate for continuous variables. Outcome comparisons were restricted to patients with documented follow-up; multivariable logistic regression was not retained because only 19 unfavorable outcomes were available and outcome ascertainment was incomplete.</p><p><strong>Results: </strong>The mean age was 48.8 ± 18.1 years and 53.7% were male. Back pain (92.6%) and radicular pain (82.6%) were the most frequent presenting symptoms. Neurological deficit was documented in 46.3% and spinal deformity in 38.0%. Lumbar involvement was most common (48.8%), followed by thoracic involvement (25.6%); anterior-column involvement occurred in 97.5%. Epidural abscess was identified in 69.4% and is reported here as a radiological finding. Microbiological or histopathological testing was performed in 46 patients; 30 were TB-positive, corresponding to 65.2% positivity among tested patients and 24.8% confirmed TB among the total cohort. Eighty-five patients (70.2%) received empirical anti-TB treatment. Among 65 patients with documented follow-up, 46 (70.8%) achieved favorable outcomes. In bivariate analysis, TB exposure history was associated with outcome (<i>p</i> = 0.003), whereas operative/procedural intervention was not significantly associated with outcome (Fisher's exact <i>p</i> = 0.399).</p><p><strong>Conclusion: </strong>Spondylodiscitis in this Somali tertiary-care cohort showed a substantial burden of neurological and radiological complications and a high proportion of empiric TB treatment. Because microbiological confirmation was limited and follow-up was incomplete, the observed confirmed TB proportion and favorable-outcome estimate should not be interpreted as population-level estimates. Prospective multicenter studies with systematic microbiological testing and complete follow-up are needed to clarify the etiological spectrum and prognostic factors.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1971442"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248329","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":"Nutrition, thyroid function, and tuberculosis: exploring the endocrine-immune axis.","authors":"Nooneh Khachatourian, Rubina Takhmazian, Vishwanath Venketaraman","doi":"10.3389/ftubr.2026.1945832","DOIUrl":"https://doi.org/10.3389/ftubr.2026.1945832","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major global health challenge, with undernutrition recognized as one of the most significant modifiable risk factors influencing disease susceptibility and clinical outcomes. Emerging evidence suggests that nutritional status may also affect TB risk indirectly through its impact on thyroid function and immune regulation. This review examines the current evidence linking nutrition, thyroid dysfunction, and susceptibility to <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>), with particular emphasis on the biological mechanisms that connect these factors. Essential micronutrients, including iodine, selenium, iron, zinc, and vitamin D, are critical for thyroid hormone synthesis, metabolism, antioxidant defense, and immune function. Deficiencies in these nutrients can impair thyroid physiology, disrupt endocrine homeostasis, and alter innate and adaptive immune responses that are essential for controlling <i>M. tuberculosis</i> infection. Thyroid hormones regulate macrophage activation, T-cell differentiation, cytokine production, immunometabolism, and oxidative stress, suggesting that thyroid dysfunction may compromise host resistance to TB. Conversely, chronic TB infection and antitubercular therapy may further disrupt thyroid function, creating a bidirectional relationship between these conditions. Collectively, the available evidence supports a conceptual framework in which nutritional deficiencies contribute to thyroid dysfunction, thyroid dysfunction impairs antimicrobial immunity, and TB further exacerbates nutritional and endocrine disturbances, establishing a self-perpetuating cycle that may increase disease susceptibility and worsen clinical outcomes. Although direct clinical evidence linking thyroid disorders with TB risk remains limited, the convergence of nutritional, endocrine, and immunological pathways provides a strong biological rationale for further investigation. Future prospective studies are needed to determine whether nutritional optimization, targeted micronutrient supplementation, and early identification and management of thyroid dysfunction can improve immune competence, reduce TB susceptibility, and enhance treatment outcomes in high-risk populations.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1945832"},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149279560","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":"High-throughput screening to identify inhibitors of the MTB CARD•RNA polymerase protein-protein interaction.","authors":"Glory M Velazquez, Jonathan Z Sexton, Scott G Franzblau, Gauri S Shetye, Akil Hossain, George A Garcia","doi":"10.3389/ftubr.2026.1937953","DOIUrl":"10.3389/ftubr.2026.1937953","url":null,"abstract":"<p><p>In 2023, tuberculosis (TB) once again became the world's deadliest infectious disease, overtaking COVID-19 as the leading cause of death from a single infectious agent, Mycobacterium tuberculosis (MTB). The World Health Organization (WHO) reports that the COVID-19 pandemic has reversed years of progress in providing essential TB services and reducing TB disease burden. In 2025, TB was responsible for an estimated 1.23 million deaths globally (95% uncertainty interval: 1.13-1.33 million), and there were 400 K cases of rifamycin resistant/multidrug resistant TB (RR, RIFR, MDR). While treatment success for drug susceptible TB remains high (88%), outcomes for MDR/RR-TB are lower but improving, reaching 71% globally. Clearly, there is a critical unmet need for novel antibiotics against MTB, exacerbated now due to COVID-19. The limited success in pursuing novel targets underscores the urgent need to revisit and reevaluate the mechanisms of action behind existing and once effective drugs, a strategy that may hold untapped potential in the fight against growing antibiotic-resistant TB. The MTB RNA polymerase (RNAP) is a proven target for TB treatment by rifampin (RMP), which kills both active and latent MTB. However, RMP suffers from several drawbacks including: long treatment times, activation of hPXR (inducing Cyp3A4 which is problematic for HIV-TB coinfection), and resistant mutations within RNAP. Two newer treatments with novel mechanisms of action include bedaquiline and delamanid, the former has been approved by the FDA for the treatment of multiple-drug resistant tuberculosis (MDR-MTB); however, even these new drugs already have incidences of acquired resistance. Our <i>goal</i> is to develop novel drug candidates for TB treatment that: target RNAP, have the potential to shorten treatment times, and have activity against RIF^R mutants. Our approach, orthogonal to the rifamycins, is to target the interaction of MTB RNAP with the required transcription factor CarD. We have previously labeled CarD with the BODIPY-FL fluorophore via engineered cysteine mutations and developed a fluorescence polarization assay to monitor its interaction with RNAP and promoter DNA. Leveraging this target, we screened a 24 K small molecule library against CarD binding to MTB RNAP. We have now extended this screening to∼88,000 additional molecules.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1937953"},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217678","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":"Adjunctive antimycobacterial and immunomodulatory effects of <i>Allium cepa</i> (pink variety) in a rabbit model of latent-like mycobacterial infection.","authors":"Theophilus Kwesi Ninkyi, Eric Ogyam, Kelvin Atta Agyapong, Cynthia Amaning Danquah","doi":"10.3389/ftubr.2026.1874315","DOIUrl":"10.3389/ftubr.2026.1874315","url":null,"abstract":"<p><strong>Introduction: </strong>Latent tuberculosis infection (LTBI) represents a major global reservoir for active disease, characterized by persistent, metabolically inactive bacilli that are difficult to eradicate. Novel therapeutic approaches targeting bacterial persistence and host immune responses are needed.</p><p><strong>Methods: </strong>A rabbit model of latent-like mycobacterial infection was established using aerosolized <i>Mycobacterium aurum</i>. The rabbits were treated with isoniazid and rifapentine (HR), ethanolic extract of <i>Allium cepa</i> (EAC), and combination therapy. Treatment efficacy was evaluated using colony-forming unit (CFU) counts and haematological parameters (WBC, neutrophils, lymphocytes).</p><p><strong>Results: </strong>The CFU counts increased significantly during the induction phase, confirming successful establishment of the latent-like mycobacterial infection model, while stabilization of bacterial load over time suggested immune-mediated containment. During the treatment phase, significant reductions in CFU counts were observed in all treated groups compared with untreated controls (<i>p</i> < 0.0001), with the greatest reduction seen in combination therapy groups (HR + <i>Allium cepa</i> extract), indicating an improved efficacy relative to monotherapy. Haematological analysis revealed significant increases in WBC, neutrophils, and lymphocytes during infection, reflecting immune activation. Treatment resulted in normalization of WBC counts, reduction in neutrophilia, and stabilization of lymphocyte levels, indicating attenuation of inflammation and restoration of immune balance.</p><p><strong>Conclusion: </strong><i>Allium cepa</i> demonstrated antimycobacterial and immunomodulatory effects in a rabbit model of latent-like mycobacterial infection and may have potential as an adjunctive therapeutic strategy in LTBI management.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1874315"},"PeriodicalIF":0.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815423","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":"Secreted proteins of <i>Mycobacterium tuberculosis</i> as therapeutic targets for drug discovery.","authors":"Anthony Musaazi Kaweesa, Divya Tiwari","doi":"10.3389/ftubr.2026.1736139","DOIUrl":"10.3389/ftubr.2026.1736139","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis (M. tuberculosis),</i> the causative agent of tuberculosis secretes proteins during the host-pathogen interaction that facilitate its survival and/or virulence within host cells. Key examples include EsxA and EsxB, CpnT/TNT, phosphatases (SapM, PtpA, PtpB), protein kinase G (PknG), the antigen 85 (ag85) complex, acyl Carrier Protein (AcpM), lipoproteins, and heat shock proteins (Hsps). Together, these secreted factors disrupt host immune responses such as phagosome maturation, antigen presentation, cytokine production, and autophagy thereby aiding in survival of these obligate intracellular bacteria. Several secreted proteins are emerging as therapeutic targets to help meet the need for shorter, more effective, and better tolerated treatment regimens for tuberculosis. Here, we review the current understanding of the major secreted proteins of <i>M. tuberculosis</i>. We also discuss progress in the discovery and development of drugs targeting these proteins. Overall, targeting <i>M.tuberculosis</i> secreted proteins remains largely in the preclinical stages of drug development. Current limitations include low potency, off-target activity, and redundancy among secreted proteins.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1736139"},"PeriodicalIF":0.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814935","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":"A <i>Mycobacterium tuberculosis</i> rare variable antigen vaccine reduces lung pathology in hypersusceptible SP140^-/- mice.","authors":"Zachary P Howard, Alexander Mohapatra, Weihao Zheng, Joel D Ernst","doi":"10.3389/ftubr.2026.1814646","DOIUrl":"10.3389/ftubr.2026.1814646","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> is the leading cause of death globally due to a single infectious agent. Currently, no licensed vaccine protects against pulmonary tuberculosis, the primary adult disease caused by Mtb infection. CD4 T cells are essential in protection against Mtb infection and inducing a protective CD4 T cell response remains the goal of most Mtb vaccines currently in testing. However, in contrast to other pathogens, most Mtb T cell epitopes do not exhibit sequence variation, suggesting that T cell recognition does not drive selection of escape mutants. We discovered hypothetical Mtb antigens that do exhibit sequence diversity within human T cell epitopes and tested the impact of vaccination with these rare variable antigens (RVMA) using a DNA vaccine platform. We found vaccination with RVMA significantly alters the immune response to Mtb infection in both C57BL/6 and hypersusceptible SP140^‒/‒ mice without reducing lung bacterial burdens. RVMA vaccination of hypersusceptible SP140^‒/‒ animals prevented necrosis and altered the lesion composition reducing tissue damage and increasing CD4 T cell distribution. Reductions in pathology were associated with increases in RORγt-expressing CD4 T cells and decreases in monocyte-derived cells in the lungs prior to the development of necrotic lesions, and were independent of B cells. These results suggest T cell responses to certain antigens may be involved in preventing pathology without significantly changing bacterial burdens and indicate that these antigens can be efficacious in Prevention of Disease TB vaccines.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1814646"},"PeriodicalIF":0.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815461","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":"Implementation of sequencing-based surveillance for drug-resistant tuberculosis in Nigeria.","authors":"Heather P McLaughlin, Israel Audu, Monday Tola, Chika Kingsley Onwuamah, Julius Ogwu, Kenneth Atoe, Chioma Nneka Kunle-Ope, Isiyaku Ahmadu, Joshua Gowon, David B Meshak, Mosunmola Iwakun, Chinedu Ejianya Ude, Modupe Abiona, Abidemi Esther Momoh, Temiloluwa Ore, Chinenye Angela Ogbu, Temitope Abigail Abiodun, Jamie Dawson, Patricia Hall-Eidson, Nnaemeka C Iriemenam, McPaul Okoye, Clement Adesigbin, Obioma Chijioke-Akaniro, Elom Emeka, Anyaike Chukwuma","doi":"10.3389/ftubr.2026.1855903","DOIUrl":"10.3389/ftubr.2026.1855903","url":null,"abstract":"<p><p>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. <i>Mycobacterium tuberculosis</i> 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.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1855903"},"PeriodicalIF":0.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814770","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":"The AcasR-FadD9 regulatory axis modulates iron homeostasis and susceptibility to the anti-mycobacterial compound ACA.","authors":"Feng Huang, Zixin Wang, Dong Jiang, Shengyi Li, Zheng-Guo He, Hua Zhang","doi":"10.3389/ftubr.2026.1830528","DOIUrl":"10.3389/ftubr.2026.1830528","url":null,"abstract":"<p><p>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 <i>acasR</i> (BCG_0932/Rv0880) conferred ACA resistance. Conversely, <i>acasR</i> overexpression increased bacterial susceptibility. Furthermore, AcasR specifically bound to and repressed the promoter of <i>fadD9</i> (Rv2590), which was its sole functionally validated target under the tested conditions. Crucially, <i>fadD9</i> 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 <i>fadD9</i> deletion. These findings reveal a novel resistance pathway in which AcasR modulates mycobacterial drug susceptibility by repressing <i>fadD9</i>, which in turn affects siderophore-mediated iron homeostasis.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1830528"},"PeriodicalIF":0.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815235","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":"Using interpretable decision trees to explore TB-HIV integration under data constraints: a proof-of-concept analysis.","authors":"Ntandazo Dlatu, Lindiwe Modest Faye, Mojisola Clara Hosu, Teke Apalata","doi":"10.3389/ftubr.2026.1853414","DOIUrl":"10.3389/ftubr.2026.1853414","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Strengthening 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Funding 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This 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 analytic","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1853414"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815284","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}