Tuberculosis最新文献

{"title":"Identification of monocyte-associated genes MSRB2, CLEC4D, and ASGR2 as potential biomarkers for tuberculosis via machine learning and mendelian randomization","authors":"Zihan Cai ,&nbsp;Yuyang Zhou ,&nbsp;Chun Bi ,&nbsp;Shoupeng Ding","doi":"10.1016/j.tube.2025.102671","DOIUrl":"10.1016/j.tube.2025.102671","url":null,"abstract":"<div><h3>Objective</h3><div>This study explores the link between immune cells and tuberculosis (TB) pathogenesis and progression, proposing diagnostic strategies based on immune microenvironment changes.</div></div><div><h3>Methods</h3><div>The CIBERSORT algorithm assessed immune cell infiltration in TB tissues, validated by routine blood tests. Differential expression analysis and WGCNA identified key genes and modules. GO and KEGG analyses elucidated biological functions. Machine learning pinpointed diagnostic biomarkers and built a predictive model. Further validation included GSVA, single-cell data, Mendelian randomization, and RT-qPCR.</div></div><div><h3>Results</h3><div>Analysis of the immune microenvironment in TB patients and healthy controls revealed monocytes as the predominant immune cell type. A total of 90 overlapping genes were identified through differential expression analysis and WGCNA. A diagnostic model incorporating MSRB2, CLEC4D, and ASGR2 was constructed using three distinct machine learning algorithms and logistic regression. Single-cell data analysis demonstrated that these three genes were predominantly expressed in mononuclear cells of TB patients. MR analysis further established a causal relationship between CLEC4D and an elevated risk of TB.</div></div><div><h3>Conclusion</h3><div>We established a monocyte-based diagnostic model demonstrating robust predictive accuracy. MSRB2, CLEC4D, and ASGR2 represent promising therapeutic targets for TB immunotherapy, providing potential breakthroughs in diagnostic precision and treatment efficacy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102671"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs in exhaled breath Condensate: Novel non-invasive biomarkers for tuberculosis diagnosis","authors":"Tak Jaya ,&nbsp;Pattnaik Bijay ,&nbsp;Rai Divyanjali ,&nbsp;Bhatraju Naveen ,&nbsp;P.P. Adwika ,&nbsp;Bangaru Sunil ,&nbsp;Sunita Yadav ,&nbsp;Sachin kumar ,&nbsp;Seetu Kumari ,&nbsp;Umashankar Verma ,&nbsp;Geetika Yadav ,&nbsp;R.S. Dhaliwal ,&nbsp;Saurabh Mittal ,&nbsp;Pawan Tiwari ,&nbsp;Vijay Hadda ,&nbsp;Karan Madan ,&nbsp;Anurag Agrawal ,&nbsp;Randeep Guleria ,&nbsp;Tapasya Srivastava ,&nbsp;Anant Mohan","doi":"10.1016/j.tube.2025.102670","DOIUrl":"10.1016/j.tube.2025.102670","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis remains a significant global health issue. Sputum smear microscopy has low sensitivity, making it difficult to diagnose. Analysis of miRNA from EBC (exhaled breath condensate) offers a potential non-invasive diagnostic method that could improve sensitivity and specificity for TB detection, including extrapulmonary TB (EPTB).</div></div><div><h3>Method</h3><div>EBC was collected from 65 treatment naïve TB patients and 65 healthy controls. miRNA profiling was done on an exploratory set (n = 40) using the qRT-PCR-based miRNome profiler kit, and shortlisted miRNAs were validated in a separate set (n = 25) using qRT-PCR. ROC curves were used to evaluate diagnostic performance.</div></div><div><h3>Result</h3><div>In this study, we identified eight differentially expressed miRNAs in TB vs healthy subjects (seven upregulated, one downregulated). Comparing PTB with EPTB, five miRNAs were upregulated and 68 miRNAs were downregulated in PTB. Between PTB and healthy controls, six miRNAs were upregulated and 16 miRNAs were downregulated in PTB, while in EPTB, 132 miRNAs were upregulated compared with controls. Validation confirmed upregulation of miR-454, miR-139, and miR-143 in tuberculosis.</div></div><div><h3>Conclusion</h3><div>The findings of our study indicate that the expression of miR-143, miR-454, and miR-139 in exhaled breath condensate has strong potential as a non-invasive biomarker for TB diagnosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102670"},"PeriodicalIF":2.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient cell model for assessing inflammatory responsive genes in Mycobacterium tuberculosis and SARS-CoV-2 co-infection","authors":"Thays Maria Costa de Lucena ,&nbsp;Débora Elienai de Oliveira Miranda ,&nbsp;Juliana Vieira de Barros Arcoverde ,&nbsp;Mariana Souza Bezerra Cavalcanti ,&nbsp;Willyenne Marilia Dantas ,&nbsp;Lindomar José Pena ,&nbsp;Virginia Maria Barros de Lorena ,&nbsp;Michelle Christiane da Silva Rabello ,&nbsp;Jaqueline de Azevedo Silva","doi":"10.1016/j.tube.2025.102672","DOIUrl":"10.1016/j.tube.2025.102672","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may induce immunopathology with extensive lung damage in hosts. To elucidate the dynamics of co-infection <em>Mtb</em> and SARS-CoV-2 and its impact on inflammatory mediators’ expression, we conducted a study to evaluate A549, lung epithelial cells, as a potential model for hosting both pathogens simultaneously. Cell infection initiated with <em>Mtb</em> H37Rv and following a 24-h incubation period, the cells were then infected with SARS-CoV-2. After a 72 h incubation period, a precision test was conducted for both pathogens, and total RNA was extracted for subsequent analysis of gene expression by RT-qPCR of the target genes: <em>IFN-γ</em>, <em>TNF-α</em>, <em>IL-6</em>, and <em>IL-1β</em>. Additionally, the levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α in the culture supernatants were measured. A549 cells are a stable and reliable cellular model for co-infection between <em>Mycobacterium tuberculosis</em> and SARS-CoV-2. Co-infection with both pathogens led to downregulation of IFN-γ, TNF-α, and IL-10, and upregulation of IL-6 and IL-1β compared to uninfected cells. A549 cells function as a cellular model for co-infection and seems a good model for elucidating host inflammatory responses in the initial site of infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102672"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring novel salivary host biomarkers for immunological diagnosis of tuberculosis: A preliminary biomarker discovery study","authors":"Pavithra Selvan ,&nbsp;Nalini Jayanthi Nagesh ,&nbsp;Leela Kakithakara Vajravelu","doi":"10.1016/j.tube.2025.102669","DOIUrl":"10.1016/j.tube.2025.102669","url":null,"abstract":"<div><div>Tuberculosis is a serious public health concern on a global scale, which emphasises the critical need for quick and precise diagnostic and treatment response monitoring techniques. In this study, Luminex multiplex immunoassay was used to detect the concentrations of 37 host biomarkers in saliva samples from 46 patients newly diagnosed with active pulmonary tuberculosis (PTB) and 46 patients with other respiratory diseases (ORD). Multiple logistic regression and the area under the receiver operator characteristics curve (AUC) were used to evaluate the diagnostic accuracy of biomarkers, which showed significant differences between the 2 groups. This study reported that Fractalkine exhibited the highest diagnostic accuracy and excellent discriminatory power, with statistically significant results (p ≤ 0.05), an AUC of 0.91, 89.1 % sensitivity and 76.1 % specificity, highlighting its strong potential to distinguish PTB cases from ORD cases. Additionally, our study found that the median levels of IL-17A, IL-23, and VEGF were statistically significant (p ≤ 0.05). General discriminant analysis further identified Fractalkine, VEGF, GM-CSF, IL-23, and IL-1α as the top five most effective biomarkers for combinations. The backward elimination approach demonstrated the potential usefulness of a four-marker combination (Fractalkine + GM-CSF + IL-23 + IL-1α) as a confirmatory diagnostic tool by achieving the greatest overall diagnostic accuracy with an AUC of 0.94 and 91.3 % specificity. Thus, combining multiple markers with high discriminating power may improve diagnostic performance and subsequently provide a more accurate, non-invasive saliva-based PTB diagnostic tool.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102669"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary and antimicrobial factor shaping extracellular bacteria dynamics in an in-host mathematical model of tuberculosis for disease control","authors":"Morufu Oyedunsi Olayiwola ,&nbsp;Ezekiel Abiodun Oluwafemi","doi":"10.1016/j.tube.2025.102668","DOIUrl":"10.1016/j.tube.2025.102668","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a global health challenge, necessitating deeper insights into the dynamics of extracellular bacterial populations within infected hosts. This study presents an in-host mathematical model that incorporates hereditary and antimicrobial factors influencing TB progression. The biological feasibility of the model is established by analyzing the boundedness of solutions within a realistic parameter space. The equilibrium states, including the disease-free and endemic equilibria, are examined, revealing conditions under which the system remains locally asymptotically stable. Sensitivity analysis is conducted to determine the key parameters driving infection dynamics, providing insights into potential control strategies. Notably, the model exhibits a backward bifurcation, indicating the possibility of multiple stable states and suggesting that reducing the basic reproduction number R₀ below unity may not be sufficient for disease eradication. These findings highlight the importance of targeted interventions to effectively control extracellular bacterial populations and mitigate TB infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102668"},"PeriodicalIF":2.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPRi-mediated repression of efflux pumps reveals Rv1258c as a key contributor to pyrazinamide resistance in Mycobacterium tuberculosis","authors":"Carlos Alonso Flores B. ,&nbsp;Kiara Aricoche-Del Campo ,&nbsp;Robert H. Gilman ,&nbsp;Mirko Zimic ,&nbsp;Patricia Sheen","doi":"10.1016/j.tube.2025.102665","DOIUrl":"10.1016/j.tube.2025.102665","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102665"},"PeriodicalIF":2.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 contributes to M.tb-induced injury and inflammation in THP-1 macrophages by mediating m6A methylation of IRF8 to activate TLR4/NF-kB pathway","authors":"Yunhua Chen ,&nbsp;Xiaolin Tang ,&nbsp;Chao He ,&nbsp;Chong Xiao ,&nbsp;Ziping Zhao","doi":"10.1016/j.tube.2025.102667","DOIUrl":"10.1016/j.tube.2025.102667","url":null,"abstract":"<div><h3>Background</h3><div>Macrophages play central roles in the immunity response to infection of intracellular bacteria, including <em>Mycobacterium tuberculosis</em> (M.tb) in tuberculosis (TB). Methyltransferase-like 3 (METTL3) has been implicated in the macrophage regulation in TB, and this study intended to investigate the molecular mechanism of METTL3 with interferon regulatory factor-8 (IRF8) in TB using <em>in vitro</em> model established by M.tb-infected THP-1 macrophages.</div></div><div><h3>Methods</h3><div>RT-qPCR and Western blot were utilized to analyze mRNA and protein expression, respectively. Cell viability, proliferation, and apoptosis were examined through cell counting kit-8 assay, EdU assay, and flow cytometry/TUNEL assay. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Methylated RNA Immunoprecipitation (MeRIP), RIP and Co-IP were performed to assess the interaction between genes.</div></div><div><h3>Results</h3><div>IRF8 knockdown alleviated injury and inflammation in M.tb-infected THP-1 macrophages. METTL3 enhanced IRF8 mRNA stability by inducing m⁶A methylation. IGF2BP1 functioned as an m⁶A reader to affect m⁶A methylation of IRF8. The function of METTL3 in M.tb-induced THP-1 macrophages was attributed to the positive regulation of IRF8. IRF8 bound to TLR4 and METTL3 could regulate TLR4 expression via targeting IRF8. IRF8/TLR4 axis promoted M.tb-induced THP-1 cell injury and inflammation. TLR4/NF-kB pathway was activated by METTL3-mediated IRF8.</div></div><div><h3>Conclusion</h3><div>These findings revealed that METTL3 expedited cell injury and inflammatory reaction in M.tb-infected THP-1 macrophages by inducing m⁶A methylation of IRF8 to activate TLR4/NF-kB pathway.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102667"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of Trace detection in Gene Xpert MTB/RIF ultra with MGIT TB culture in a high TB-endemic Country","authors":"Swapna Naik,&nbsp;Sweta Dhaneja,&nbsp;Archana Khilari,&nbsp;Shaoli Basu,&nbsp;Anjali Shetty,&nbsp;Camilla Rodrigues","doi":"10.1016/j.tube.2025.102666","DOIUrl":"10.1016/j.tube.2025.102666","url":null,"abstract":"<div><h3>Background</h3><div>The Gene Xpert MTB/RIF Ultra is a Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) for rapid detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) drug susceptibility testing (DST) pattern.</div></div><div><h3>Objective</h3><div>1)To compare the culture results of samples detected as a Trace on Gene Xpert MTB/RIF Ultra with MTB growth in liquid culture. 2) To compare the rifampicin indeterminate results from Gene Xpert MTB/RIF Ultra with MGIT RIF DST pattern.</div></div><div><h3>Materials and Methods</h3><div>A retrospective case record study was conducted from January 1, 2020 to August 31, 2024. Samples were evaluated using Gene Xpert MTB/RIF Ultra and MGIT liquid culture. MTB isolates from MGIT liquid culture were subjected to MGIT RIF DST.</div></div><div><h3>Result</h3><div>A total of 1821 samples detected as trace in Gene Xpert MTB/RIF Ultra, 538 (29.54 %) grew in MGIT liquid culture, while 1283 (70.46 %) did not grow. Among the 538 Trace detected samples with RIF indeterminate results, a comparison with MGIT RIF DST revealed that 451 (83.83 %) were rifampicin sensitive, while 87 (16.17 %) were rifampicin resistance. 49 (9.10 %) of these were pulmonary samples, while 489 (90.90 %) were extrapulmonary samples.</div></div><div><h3>Conclusion</h3><div>Gene Xpert MTB/RIF Ultra is more rapid, more sensitive, less specific and more cost-effective compared to MGIT liquid culture.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102666"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo antibacterial activity of sudapyridine (WX-081) combined with other drugs against Mycobacterium abscessus","authors":"Hong Wang ,&nbsp;Luyao Zheng ,&nbsp;Lei Fu ,&nbsp;Weiyan Zhang ,&nbsp;Shaoyu Dong ,&nbsp;Xiaoyou Chen ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102655","DOIUrl":"10.1016/j.tube.2025.102655","url":null,"abstract":"<div><div>The management of <em>Mycobacterium abscessus</em> (MAB) infection presents formidable challenges, necessitating the development of innovative antimicrobial agents and more efficacious combination therapies. The objective of this study was to investigate the <em>in vitro</em>, <em>intracellular</em>, and <em>in vivo</em> antibacterial activity of sudapyridine (WX-081) in combination with clarithromycin (CLR), clofazimine (CFZ), rifabutin (RFB), and linezolid (LZD) against MAB. <em>In vitro</em>, the interaction between WX-081 and other drugs was assessed using the checkerboard method against MAB. Synergistic or additive effects were observed when combining WX-081 with other drugs against all strains tested. The intracellular activity of WX-081 in combination with CLR, CFZ, RFB, and LZD against the MAB reference strain in J774A.1 cells was evaluated. The combination of WX-081 and CFZ or RFB exhibited potent inhibitory activity against MAB in macrophages. To evaluate pharmacodynamics, immunosuppressed BALB/c mice were infected with MAB to establish a murine model for assessing two-drug and three-drug combinations. <em>In vivo</em> studies demonstrated that the combination of WX-081 with CLR or both CLR and CFZ displayed antibacterial activity and significantly prevented mouse mortality. Our study demonstrates that the concurrent use of WX-081 with CLR or CLR plus CFZ holds significant promise as a clinical intervention for MAB infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102655"},"PeriodicalIF":2.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo activities of a novel benzothiopyranone candidate NTB-3119M against Mycobacterium tuberculosis","authors":"Manyi Xu ,&nbsp;Lei Zhang ,&nbsp;Bin Wang ,&nbsp;Lei Fu ,&nbsp;Shaochen Guo ,&nbsp;Xi Chen ,&nbsp;Weiyan Zhang ,&nbsp;Gang Li ,&nbsp;Peng Li ,&nbsp;Haihong Huang ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102654","DOIUrl":"10.1016/j.tube.2025.102654","url":null,"abstract":"<div><h3>Objectives</h3><div>NTB-3119M, a novel benzothiopyranone derivative identified through comprehensive drug development studies, was selected as a promising antituberculosis (anti-TB) candidate. This study systematically evaluated its anti-TB efficacy <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div><em>In vitro</em> analyses encompassed antimicrobial susceptibility testing to determine minimum inhibitory concentrations (MICs) against <em>Mycobacterium tuberculosis</em> H37Rv, 10 drug-susceptible clinical isolates, and 30 multidrug-resistant (MDR) strains, alongside evaluations of minimal bactericidal concentrations (MBCs) using H37Rv and seven clinical isolates. Additionally, intracellular anti-mycobacterial activity was assessed in H37Rv-infected macrophages, and cytotoxicity was profiled through MTT assays on Vero cells. <em>In vivo</em> studies utilized acute and chronic murine tuberculosis infection models to investigate the dose-dependent efficacy of NTB-3119M (50 and 100 mg/kg) against H37Rv, with concurrent comparative histopathological analysis of lung and spleen tissues.</div></div><div><h3>Results</h3><div>NTB-3119M demonstrated superior <em>in vitro</em> potency against both drug-sensitive and drug-resistant <em>M. tuberculosis</em> strains compared to first-line agents, Isoniazid (INH), Rifampicin (RIF), Moxifloxacin (MOFX), Levofloxacin (LVFX), and Streptomycin (SM), exhibiting comparable activity to PBTZ169. Time-kill curves for NTB-3119M indicate its potent bactericidal activity. Meanwhile, No cytotoxicity was observed on Vero cells. Spontaneous resistant mutants of NTB-3119M appears at a frequency of 6.44 × 10⁻⁷ to 3.65 × 10⁻⁶. Most importantly, NTB-3119M demonstrates comparable activity of PBTZ169 and better bactericidal activity against <em>M. tuberculosis</em> than INH and RIF in the 50- and 100- mg/kg groups in acute and chronic murine models.</div></div><div><h3>Conclusion</h3><div>Our research provided comprehensive evidence that NTB-3119M with increased water solubility and bioavailability based on previous research performed excellent anti-tuberculosis activity and less cytotoxicity, which effectively tackled the undesirable drug properties associated with previous benzothiopyrone derivatives. It is warranted that NTB-3119M, as a highly promising candidate anti tuberculosis drug, deserves further research and clinical trial.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102654"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}