Pub Date : 2025-07-23DOI: 10.1016/j.tube.2025.102675
Yong-Soon Cho , Rannissa Puspita Jayanti , Hyun-Kyung Lee , Hyo-Jung Kim , Tae Won Jang , Yun Seok Kim , Yousang Ko , Jinsoo Min , Heayon Lee , Soedarsono Soedarsono , Hyeon-Jeong Seong , Young-Kyung Choi , Ho-Sook Kim , Dong Hyun Kim , Jae-Gook Shin , cPMTb
Background
Levofloxacin (LFX) has gained attention as an effective drug to reduce treatment duration in tuberculosis (TB). We aimed to evaluate factors related to interindividual variability (IIV) and describe the pharmacokinetics (PK) of LFX in both DS- and DR-TB, as well as explore the optimal dose for TB treatment.
Methods
We included demographics, clinical information, and LFX concentrations from multinational hospitals. All data were utilized for model establishment. The population PK model was built using nonlinear mixed-effects method. Dose simulation was carried out thereafter using Monte Carlo simulation.
Results
A one-compartment model with allometric scaling described LFX PK adequately. PK parameters were similar between DS- and DR-TB. eGFR significantly affected CL/F, which decreased by 22 % and 48 % in mild and moderate-severe renal impairment, respectively (normal CL/F: 6.6 L/h). Considering LFX's AUC/MIC target of 146 and epidemiological cut-off value of MIC 0.5 μg/mL, doses of 1000 mg, 1250 mg, and 1500 mg may achieve 90 % probability of target attainment in patients with normal renal function weighing <40 kg, 40–70 kg, and >70 kg, respectively.
Conclusion
Renal impairment reduced LFX clearance. Doses equal to or greater than 1000 mg may improve AUC/MIC target attainment but require cautious use considering safety and clinical efficacy.
{"title":"Population pharmacokinetics of levofloxacin in drug-susceptible and drug-resistant tuberculosis patients: Optimal dose suggestion based on renal function","authors":"Yong-Soon Cho , Rannissa Puspita Jayanti , Hyun-Kyung Lee , Hyo-Jung Kim , Tae Won Jang , Yun Seok Kim , Yousang Ko , Jinsoo Min , Heayon Lee , Soedarsono Soedarsono , Hyeon-Jeong Seong , Young-Kyung Choi , Ho-Sook Kim , Dong Hyun Kim , Jae-Gook Shin , cPMTb","doi":"10.1016/j.tube.2025.102675","DOIUrl":"10.1016/j.tube.2025.102675","url":null,"abstract":"<div><h3>Background</h3><div>Levofloxacin (LFX) has gained attention as an effective drug to reduce treatment duration in tuberculosis (TB). We aimed to evaluate factors related to interindividual variability (IIV) and describe the pharmacokinetics (PK) of LFX in both DS- and DR-TB, as well as explore the optimal dose for TB treatment.</div></div><div><h3>Methods</h3><div>We included demographics, clinical information, and LFX concentrations from multinational hospitals. All data were utilized for model establishment. The population PK model was built using nonlinear mixed-effects method. Dose simulation was carried out thereafter using Monte Carlo simulation.</div></div><div><h3>Results</h3><div>A one-compartment model with allometric scaling described LFX PK adequately. PK parameters were similar between DS- and DR-TB. eGFR significantly affected CL/F, which decreased by 22 % and 48 % in mild and moderate-severe renal impairment, respectively (normal CL/F: 6.6 L/h). Considering LFX's AUC/MIC target of 146 and epidemiological cut-off value of MIC 0.5 μg/mL, doses of 1000 mg, 1250 mg, and 1500 mg may achieve 90 % probability of target attainment in patients with normal renal function weighing <40 kg, 40–70 kg, and >70 kg, respectively.</div></div><div><h3>Conclusion</h3><div>Renal impairment reduced LFX clearance. Doses equal to or greater than 1000 mg may improve AUC/MIC target attainment but require cautious use considering safety and clinical efficacy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102675"},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724164","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}
Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate prevalence estimates are lacking due to the absence of nationwide surveillance. Non-tuberculous mycobacteria have been reported in clinically healthy cattle and wildlife globally, complicating tuberculosis (TB) diagnostics and surveillance. This study aimed to characterize NTM species isolated from tissue samples of slaughtered cattle in Chennai using culture and targeted hsp65 gene sequencing. A total of 118 presumed NTM samples from 115 animals were processed, and 49 isolates were confirmed as NTMs by PCR. Sequencing identified 18 different species, with Mycobacterium intracellulare (9/49) being the most frequent, followed by Mycobacterium sp. strain 79_MI18_10584 (6/49) and Mycobacterium elephantis (6/49). Several identified species, including M. intracellulare, M. fortuitum (5/49), M. kansasii (4/49), and M. avium, have caused infections in humans as well. NTMs in cattle lymph nodes without visible lesions suggest their asymptomatic persistence, albeit there being a possibility of transient colonization. Non-tuberculous mycobacteria complicate bovine tuberculosis (bTB) diagnostics by inducing cross-reactive immune responses and forming granulomatous lesions resembling those caused by Mycobacterium tuberculosis complex (MTBC). This study highlights the presence and diversity of NTMs in Indian cattle and emphasizes the need for better surveillance, improved molecular characterization, and better understanding of their epidemiological and immunological roles in both veterinary and public health contexts.
{"title":"Identification of non-tuberculous mycobacteria in slaughtered cattle from Chennai, India","authors":"Harini Ramanujam , Manohar Nesakumar , Kannan Thiruvengadam , Rajaraman Kannan , Sivaraman Palanisamy , Sivakumar Shanmugam , Kannan Palaniyandi","doi":"10.1016/j.tube.2025.102673","DOIUrl":"10.1016/j.tube.2025.102673","url":null,"abstract":"<div><div>Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate prevalence estimates are lacking due to the absence of nationwide surveillance. Non-tuberculous mycobacteria have been reported in clinically healthy cattle and wildlife globally, complicating tuberculosis (TB) diagnostics and surveillance. This study aimed to characterize NTM species isolated from tissue samples of slaughtered cattle in Chennai using culture and targeted <em>hsp65</em> gene sequencing. A total of 118 presumed NTM samples from 115 animals were processed, and 49 isolates were confirmed as NTMs by PCR. Sequencing identified 18 different species, with <em>Mycobacterium intracellulare</em> (9/49) being the most frequent, followed by <em>Mycobacterium</em> sp. <em>strain 79_MI18_10584</em> (6/49) and <em>Mycobacterium elephantis</em> (6/49). Several identified species, including <em>M. intracellulare, M. fortuitum</em> (5/49)<em>, M. kansasii</em> (4/49)<em>, and M. avium</em>, have caused infections in humans as well. NTMs in cattle lymph nodes without visible lesions suggest their asymptomatic persistence, albeit there being a possibility of transient colonization. Non-tuberculous mycobacteria complicate bovine tuberculosis (bTB) diagnostics by inducing cross-reactive immune responses and forming granulomatous lesions resembling those caused by <em>Mycobacterium tuberculosis</em> complex (MTBC). This study highlights the presence and diversity of NTMs in Indian cattle and emphasizes the need for better surveillance, improved molecular characterization, and better understanding of their epidemiological and immunological roles in both veterinary and public health contexts.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102673"},"PeriodicalIF":2.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722939","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}
Pub Date : 2025-07-03DOI: 10.1016/j.tube.2025.102671
Zihan Cai , Yuyang Zhou , Chun Bi , Shoupeng Ding
Objective
This study explores the link between immune cells and tuberculosis (TB) pathogenesis and progression, proposing diagnostic strategies based on immune microenvironment changes.
Methods
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.
Results
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.
Conclusion
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.
{"title":"Identification of monocyte-associated genes MSRB2, CLEC4D, and ASGR2 as potential biomarkers for tuberculosis via machine learning and mendelian randomization","authors":"Zihan Cai , Yuyang Zhou , Chun Bi , 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}
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).
Method
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.
Result
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.
Conclusion
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.
{"title":"MicroRNAs in exhaled breath Condensate: Novel non-invasive biomarkers for tuberculosis diagnosis","authors":"Tak Jaya , Pattnaik Bijay , Rai Divyanjali , Bhatraju Naveen , P.P. Adwika , Bangaru Sunil , Sunita Yadav , Sachin kumar , Seetu Kumari , Umashankar Verma , Geetika Yadav , R.S. Dhaliwal , Saurabh Mittal , Pawan Tiwari , Vijay Hadda , Karan Madan , Anurag Agrawal , Randeep Guleria , Tapasya Srivastava , 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}
Pub Date : 2025-07-01DOI: 10.1016/j.tube.2025.102672
Thays Maria Costa de Lucena , Débora Elienai de Oliveira Miranda , Juliana Vieira de Barros Arcoverde , Mariana Souza Bezerra Cavalcanti , Willyenne Marilia Dantas , Lindomar José Pena , Virginia Maria Barros de Lorena , Michelle Christiane da Silva Rabello , Jaqueline de Azevedo Silva
Mycobacterium tuberculosis (Mtb) 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 Mtb 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 Mtb 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: IFN-γ, TNF-α, IL-6, and IL-1β. 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 Mycobacterium tuberculosis 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.
{"title":"Efficient cell model for assessing inflammatory responsive genes in Mycobacterium tuberculosis and SARS-CoV-2 co-infection","authors":"Thays Maria Costa de Lucena , Débora Elienai de Oliveira Miranda , Juliana Vieira de Barros Arcoverde , Mariana Souza Bezerra Cavalcanti , Willyenne Marilia Dantas , Lindomar José Pena , Virginia Maria Barros de Lorena , Michelle Christiane da Silva Rabello , 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}
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.
{"title":"Exploring novel salivary host biomarkers for immunological diagnosis of tuberculosis: A preliminary biomarker discovery study","authors":"Pavithra Selvan , Nalini Jayanthi Nagesh , 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}
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.
{"title":"Hereditary and antimicrobial factor shaping extracellular bacteria dynamics in an in-host mathematical model of tuberculosis for disease control","authors":"Morufu Oyedunsi Olayiwola , 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 R<sub>0</sub> 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}
Pub Date : 2025-06-19DOI: 10.1016/j.tube.2025.102665
Carlos Alonso Flores B. , Kiara Aricoche-Del Campo , Robert H. Gilman , Mirko Zimic , Patricia Sheen
{"title":"CRISPRi-mediated repression of efflux pumps reveals Rv1258c as a key contributor to pyrazinamide resistance in Mycobacterium tuberculosis","authors":"Carlos Alonso Flores B. , Kiara Aricoche-Del Campo , Robert H. Gilman , Mirko Zimic , 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}
Macrophages play central roles in the immunity response to infection of intracellular bacteria, including Mycobacterium tuberculosis (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 in vitro model established by M.tb-infected THP-1 macrophages.
Methods
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.
Results
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.
Conclusion
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.
{"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 , Xiaolin Tang , Chao He , Chong Xiao , 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 m<sup>6</sup>A methylation. IGF2BP1 functioned as an m<sup>6</sup>A reader to affect m<sup>6</sup>A 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 m<sup>6</sup>A 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}
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.
Objective
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.
Materials and Methods
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.
Result
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.
Conclusion
Gene Xpert MTB/RIF Ultra is more rapid, more sensitive, less specific and more cost-effective compared to MGIT liquid culture.
{"title":"Correlation of Trace detection in Gene Xpert MTB/RIF ultra with MGIT TB culture in a high TB-endemic Country","authors":"Swapna Naik, Sweta Dhaneja, Archana Khilari, Shaoli Basu, Anjali Shetty, 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}
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