Tuberculosis: Recent Updates in Basic Research, Drug Discovery and Treatment

Ameya Bendre^1*Pooja Singh^2*Swati Jaiswal³

• ¹Department of Chemistry, S. P. Pune University (formerly known as Pune University), Ganeshkhind, Pune 411007, India, Pune, India
• ²Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Al, United States, Birmingham, United States
• ³University of Massachusetts Chan Medical School Department of Medicine, Worcester, United States

Tuberculosis: Recent Updates in Basic Research, Drug Discovery and Treatment Ameya D. Bendre1, Pooja Singh2*, Swati Jaiswal3* 1.Department of Chemistry, S. P. Pune University (formerly known as Pune University), Ganeshkhind, Pune 411007, India Current affiliation: Gennova Biopharmaceuticals Ltd, Pune 411057, India 2.Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, AL, United States 3.Department of Medicine, UMass Chan Medical School, Worcester, MA, United States * Corresponding authors Keywords: Tuberculosis, Extra-pulmonary tuberculosis, Co-infections, Molecular diagnosis, machine learning Tuberculosis (TB) remains a persistent and formidable global health threat. According to the World Health Organization’s most recent Global Tuberculosis Report, 10.8 million people developed TB in 2023, with 1.25 million lives lost to this preventable and curable disease (WHO, 2024). Despite decades of concerted effort and the ambitious goals of the WHO’s End TB Strategy, which seeks to reduce TB deaths by 90% and TB incidence by 80% by 2030 (Floyd et al., 2018), the worldwide burden of TB remains alarmingly high. The COVID-19 pandemic has further complicated TB control efforts, disrupting essential detection and treatment programs, and leading to increased morbidity and mortality (Chanda-Kapata et al., 2022; Dheda et al., 2022). Many of the gains achieved in TB control over the past decade have been eroded, and there is now a resurgence of TB in several high-burden regions. In this context, there is a renewed urgency to re-examine our strategies, foster innovation, and strengthen collaboration in TB research and care. Our current research topic- Tuberculosis: Recent Updates in Basic Research, Drug Discovery and Treatment, aims to promote both clinical and basic research focused on TB treatment, disease management, drug discovery, and how Mycobacterium tuberculosis (M. tuberculosis) adapts metabolically to different therapies. Key areas include understanding TB pathogenesis, developing new drugs and treatments, advancing vaccines and diagnostics, exploring innovative approaches for multidrug- and extensively drug-resistant TB, and investigating the molecular and genetic factors that influence mycobacterial responses to therapy, all to improve TB diagnosis, treatment, and global control. A comprehensive approach to TB must encompass not only the classic pulmonary form but also the growing complexity of extrapulmonary TB and its frequent intersection with other chronic conditions. Deepening our understanding of TB pathogenesis, how M. tuberculosis infects, persists, and escapes immune surveillance, is fundamental to developing new therapeutic targets, more effective vaccines, and host-directed therapies. The dynamic interplay between bacterial virulence and host immunity largely determines whether TB remains latent or progresses to active disease. The pivotal study by Jinyi He and colleagues employs bioinformatics and systems biology to investigate the biological links between chronic hepatitis B virus (HBV) infection and TB (https://doi.org/10.3389/fmed.2025.1519216). He et al. (2025) identified 35 shared genes involved in immune regulation and metabolism, revealing molecular pathways that may explain the increased risk of TB reactivation and adverse outcomes in HBV co-infected individuals (He et al., 2025). These insights highlight the need for integrated management strategies, as immunosuppression or drug interactions can complicate the clinical course of both diseases. Adding to the understanding of host-pathogen interactions, Anna Starshinova’s review highlights immune-neuroendocrine reactivity during pregnancy, a state that alters maternal immunity and increases vulnerability to TB (https://doi.org/10.3389/fmed.2025.1503402). Pregnancy introduces unique immunological challenges for TB management. Hormonal changes during pregnancy shift the immune system toward an anti-inflammatory state, suppressing the T cell responses essential for TB control. This increases susceptibility to new TB infections and reactivation of latent disease, often resulting in atypical or subtle clinical presentations. The immune suppression peaks during labor and rebounds postpartum, influencing both TB progression and diagnostic reliability. These findings underscore the need for tailored screening and vigilant monitoring of pregnant women at risk for TB (Starshinova et al., 2025). The complex interplay between TB and lung cancer is examined in a comprehensive review by Chunju Fang (https://doi.org/10.3389/fimmu.2025.1561719). Lung cancer patients are particularly susceptible to developing active TB, especially when treated with immunosuppressive agents such as immune checkpoint inhibitors (Fang et al., 2025). The bidirectional relationship between TB and lung cancer is now well recognized. Conversely, a history of TB increases the risk of lung cancer and is associated with poorer outcomes. Both diseases foster immunosuppressive microenvironments, characterized by regulatory T cells, myeloid-derived suppressor cells, and inhibitory cytokines, that undermine effective immune responses. Advances in spatial multi-omics are beginning to unravel these complex cellular interactions, paving the way for innovative therapies targeting shared mechanisms of immune evasion and chronic inflammation. Accurate and timely diagnosis is the cornerstone of effective TB control, yet it remains a significant challenge, particularly for extrapulmonary TB and in resource-limited settings. While chest X-ray (CXR) has long been the mainstay for pulmonary TB detection, its variable sensitivity and specificity often result in delayed or missed diagnoses. Fortunately, recent advances in technology are transforming TB diagnostics. Two articles featured in this research topic critically examine the limitations of CXR and highlight emerging diagnostic modalities poised to address these gaps. Nanotechnology, for example, is revolutionizing the detection of bone and joint TB, a notoriously difficult form to diagnose early (https://doi.org/10.3389/fmed.2025.1536547). Palladium-platinum bimetallic nanoparticles (Pd@Pt NPs) incorporated into paper-based diagnostic devices can now detect M. tuberculosis DNA in bone and joint samples within minutes, offering rapid, sensitive, and portable solutions for early diagnosis in even the most remote settings (Ding et al., 2025). Another study by Giacomo Guido evaluates the comparative effectiveness of chest ultrasound, conventional chest X-ray, and AI-supported computer-aided diagnosis (CAD) for early TB detection in resource-limited environments, in the Ethiopian population, where the TB burden is highest (https://doi.org/10.3389/fpubh.2024.1476866). For pulmonary TB, the limitations of CXR have also prompted the exploration of alternative imaging modalities and artificial intelligence-driven solutions (Guido et al., 2024). Chest ultrasonography (CUS) provides a portable, radiation-free, and cost-effective alternative, while computer-aided diagnostic (CAD) systems use machine learning to enhance the accuracy and consistency of CXR interpretation. On the diagnostic technology front, Yu-Qi Hu’s meta-analysis of fluorescence in situ hybridization (FISH) demonstrates high sensitivity and specificity for pulmonary TB detection, especially in low-incidence settings, advocating for its potential role as a rapid, cost-effective diagnostic adjunct (Hu et al., 2025; https://doi.org/10.3389/fmed.2024.1467530). Beyond technological advances, TB is increasingly recognized as a complex, multisystem disease that often coexists with other chronic conditions. Zhou et al. (2025) reported a compelling case of a patient with both acute miliary pulmonary TB and immunoglobulin G4-related kidney disease (IgG4-RKD) (Zhou et al., 2025; https://doi.org/10.3389/fimmu.2024.1493754). The overlapping clinical and laboratory features required a comprehensive diagnostic evaluation, but early recognition and individualized treatment led to full recovery—underscoring the importance of considering TB in the differential diagnosis of unexplained inflammatory or fibrotic diseases, especially in endemic areas. Advances in Tuberculosis Diagnostics and Control As we navigate the post-pandemic era, advancing tuberculosis diagnostics and control requires the integration of basic science, technological innovation, and clinical research. The convergence of TB with immune-mediated, viral, oncologic, and reproductive conditions calls for a more nuanced and multidisciplinary approach to care. Recent studies highlight progress in areas such as molecular co-infections, immune interactions, nanoparticle-based therapies, and AI-driven diagnostics—collectively paving the way for more effective and targeted interventions. Early recognition, personalized treatment, and collaborative research are essential to improve outcomes in high-risk populations. This special issue underscores the importance of sustained innovation and cross-disciplinary efforts to accelerate progress toward the WHO’s End TB goals and address the evolving challenges of TB in an increasingly complex global health landscape. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Credit Author Statement Ameya Bendre: Conceptualization, Writing – original draft, Writing – review & editing. Pooja Singh: Conceptualization, Writing – original draft, Writing – review & editing. Swati Jaiswal: Conceptualization, Writing – original draft, Writing – review & editing. 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