Tuberculosis最新文献

{"title":"METTL3-deficiency m6A-dependently degrades MALAT1 to suppress NLRP3-mediated pyroptotic cell death and inflammation in Mycobacterium tuberculosis (H37Ra strain)-infected mouse macrophages","authors":"Limei Han,&nbsp;Nueramina Tieliwaerdi,&nbsp;Xin Li","doi":"10.1016/j.tube.2024.102502","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102502","url":null,"abstract":"<div><p><em>Mycobacterium tuberculosis</em> (Mtb)-infected macrophages aggravated the development of pulmonary tuberculosis, but its detailed molecular mechanisms are still largely unknown. Here, the mouse primary peritoneal macrophages were infected with the attenuated strain of Mtb H37Ra, and we firstly verified that targeting a novel METTL3/N6-Methyladenosine (m6A)/LncRNA MALAT1/miR-125b/TLR4 axis was effective to suppress pyroptotic cell death in the Mtb-infected macrophages. Specifically, through performing Real-Time qPCR and Western Blot analysis, we validated that METTL3, LncRNA MALAT1 and TLR4 were elevated, whereas miR-125b and the anti-oxidant agents (Nrf2 and HO-1) were downregulated in Mtb-infected mouse macrophages. In addition, functional experiments confirmed that both ROS scavenger NAC and METTL3-ablation downregulated NLRP3, GSDMD-C, cleaved Caspase-1 and ASC to restrain pyroptotic cell death and decreased the expression levels of IL-1β, IL-18, IL-6 and TNF-α to restrain inflammatory cytokines expression in Mtb-infected macrophages. Next, METTL3-ablation induced m6A-demethylation and instability in LncRNA MALAT1, and low-expressed LncRNA MALAT1 caused TLR4 downregulation through sponging miR-125b, resulting in the inactivation of NLRP3 inflammasome. Finally, silencing of METTL3-induced protective effects in Mtb-infected macrophages were all abrogated by overexpressing LncRNA MALAT1 and downregulating miR-125b. Thus, we concluded that targeting METTL3-mediated m6A modifications suppressed Mtb-induced pyroptotic cell death in mouse macrophages, and the downstream LncRNA MALAT1/miR-125b/TLR4 axis played critical role in this process.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102502"},"PeriodicalIF":3.2,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062965","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":"Trends of type 2 diabetes with pulmonary tuberculosis patients,2013–2022, and changes after the coronavirus disease 2019 (COVID-19) pandemic","authors":"Zijian Wang ,&nbsp;Sheng Zhao ,&nbsp;Aiping Zhang ,&nbsp;Bin Quan,&nbsp;Chun Duan,&nbsp;Manman Liang,&nbsp;Janghua Yang","doi":"10.1016/j.tube.2024.102499","DOIUrl":"10.1016/j.tube.2024.102499","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;To describe the trends of Type 2 Diabetes with Pulmonary Tuberculosis (T2DM-TB) patients from 2013 to 2022 and to investigate the impact of COVID-19 lockdown on glycemic control and associated factors in T2DM-TB.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this population-based study of the First Affiliated Yijishan Hospital of Wannan Medical College in China, we described the 10-year trends of patients diagnosed with T2DM-TB. We included patients diagnosed with TB, T2DM-TB and T2DM-TB patients for comparative analysis, aged 15 years or older. Data were missing, and both multidrug-resistant (MDR) TB patients and non-T2DM patients were excluded from our study.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We pooled Type 2 Diabetes (T2DM) and Tuberculosis (TB) data from The First Affiliated Yijishan Hospital of Wannan Medical College in China, gathered between January 1, 2013, and December 31, 2022. The data included 14,227 T2DM patients, 6130 TB patients, and 982 T2DM-TB patients. During the past 10 years, the number of inpatients with TB decreased, while the number of patients with T2DM and T2DM-TB increased year by year. To rule out any influence factors, we analyzed the ratio of the three groups. The ratio of TB/T2DM decreased year by year (p &lt; 0.05), while the ratio of TB-T2DM/TB increasing year by year (p = 0.008). During the COVID-19 epidemic period, there was no significant change in the ratio of TB-T2DM/T2DM (p = 0.156). There was no significant change in the proportion of male patients with TB and TB-T2DM (p = 0.325; p = 0.190), but the proportion of male patients with T2DM showed an increasing trend (p &lt; 0.001). The average age of TB patients over the past 10 years was 54.5 ± 18.4 years and showed an increasing trend year by year (p &lt; 0.001). However, there was no significant change in the age of T2DM or TB-T2DM patients (p = 0.064; p = 0.241). Patients data for the first (2013–2017) and the last (2018–2022) five years were compared. We found that the number of T2DM and TB-T2DM in the last five years was significantly higher than in the first five years, but the number of TB was significantly lower than in the first five years. There is a significant statistical difference in the proportion of TB/T2DM and TB-T2DM/TB, which is similar to the previous results. The average age (56.0 ± 17.6 years) of TB patients in the last five years is significantly higher than in the first five years (53.1 ± 18.9) (p &lt; 0.001). The number of male patients with T2DM in the last five years is higher than that in the first five years, with significant difference (p &lt; 0.001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The trends of T2DM-TB among hospitalized TB patients have increased significantly over the past 10 years, which may be related to the increase in the number of T2DM cases. The COVID-19 pandemic has been effective in controlling the transmission of TB, but it has been detrimental to the control of T2DM. Male patients with T2DM and el","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102499"},"PeriodicalIF":3.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000258/pdfft?md5=f6763ace09806162da3a641c584d5040&pid=1-s2.0-S1472979224000258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational drug repositioning identifies niclosamide and tribromsalan as inhibitors of Mycobacterium tuberculosis and Mycobacterium abscessus","authors":"Jeremy J. Yang ,&nbsp;Aaron Goff ,&nbsp;David J. Wild ,&nbsp;Ying Ding ,&nbsp;Ayano Annis ,&nbsp;Randy Kerber ,&nbsp;Brian Foote ,&nbsp;Anurag Passi ,&nbsp;Joel L. Duerksen ,&nbsp;Shelley London ,&nbsp;Ana C. Puhl ,&nbsp;Thomas R. Lane ,&nbsp;Miriam Braunstein ,&nbsp;Simon J. Waddell ,&nbsp;Sean Ekins","doi":"10.1016/j.tube.2024.102500","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102500","url":null,"abstract":"<div><p>Tuberculosis (TB) is still a major global health challenge, killing over 1.5 million people each year, and hence, there is a need to identify and develop novel treatments for <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>). The prevalence of infections caused by nontuberculous mycobacteria (NTM) is also increasing and has overtaken TB cases in the United States and much of the developed world. <em>Mycobacterium abscessus (M. abscessus)</em> is one of the most frequently encountered NTM and is difficult to treat. We describe the use of drug-disease association using a semantic knowledge graph approach combined with machine learning models that has enabled the identification of several molecules for testing anti-mycobacterial activity. We established that niclosamide (<em>M. tuberculosis</em> IC₉₀ 2.95 μM; <em>M. abscessus</em> IC₉₀ 59.1 μM) and tribromsalan (<em>M. tuberculosis</em> IC₉₀ 76.92 μM; <em>M. abscessus</em> IC₉₀ 147.4 μM) inhibit <em>M. tuberculosis</em> and <em>M. abscessus in vitro</em>. To investigate the mode of action, we determined the transcriptional response of <em>M. tuberculosis</em> and <em>M. abscessus</em> to both compounds in axenic log phase, demonstrating a broad effect on gene expression that differed from known <em>M. tuberculosis</em> inhibitors. Both compounds elicited transcriptional responses indicative of respiratory pathway stress and the dysregulation of fatty acid metabolism.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102500"},"PeriodicalIF":3.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S147297922400026X/pdfft?md5=55713d804b4f2ee2b52938a2411c9b61&pid=1-s2.0-S147297922400026X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment","authors":"Febriana Catur Iswanti ,&nbsp;Kurnia Maidarmi Handayani ,&nbsp;Ardiana Kusumaningrum ,&nbsp;Tomohiko Yamazaki ,&nbsp;Diah Handayani ,&nbsp;Mohamad Sadikin","doi":"10.1016/j.tube.2024.102498","DOIUrl":"10.1016/j.tube.2024.102498","url":null,"abstract":"<div><p>Drug resistance to tuberculosis (TB) has become an obstacle in eliminating tuberculosis. The transmission of drug-resistant TB from patients increases the incidence of primary drug-resistant (DR) TB in individuals who are in close contact. Therefore, it is necessary to incorporate an immunological approach into preventive therapy. This study focuses on the activity of lysosomal enzymes, oxygen bursts, and the attachment ability of macrophages among individuals diagnosed with active drug-resistant TB compared with close contacts with latent TB or healthy cases. We measured macrophage oxygen burst ability (Water-soluble tetrazolium salt (WST) test, Nitric Oxide production, and myeloperoxidase activity) and the degradative ability of lysosomes (activity of the β-glucuronidase and acid phosphatase enzymes). Six active DR-TB patients and 18 close-contact cases (8 Latent Tuberculosis Infection (LTBI); 10 healthy) were recruited at Universitas Indonesia Hospital. The macrophage attachment of the LTBI group was higher than in the other groups. NO production, myeloperoxidase activity, β-glucuronidase, and acid phosphatase were higher in the active DR-TB group. A negative correlation was uncovered between phagocytosis and NO production, myeloperoxidase activity, and lysosomal enzymes. The difference in macrophage function is expected to be a further reference in active DR-TB treatment or preventive therapy.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102498"},"PeriodicalIF":3.2,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000246/pdfft?md5=15ba43fa91118601eebf75ab840f7b87&pid=1-s2.0-S1472979224000246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid immune responsive gene regulation in Mycobacterium tuberculosis infection in vitro","authors":"Maria Eduarda de Albuquerque Borborema ,&nbsp;Débora Elienai de Oliveira Miranda ,&nbsp;Thays Maria Costa de Lucena ,&nbsp;Virgínia Maria Barros de Lorena ,&nbsp;Michelle Christiane da Silva Rabello ,&nbsp;Jaqueline de Azevêdo Silva","doi":"10.1016/j.tube.2024.102497","DOIUrl":"10.1016/j.tube.2024.102497","url":null,"abstract":"<div><p>Tuberculosis (TB) is an infectious disease displaying a multifactorial pathology. The immunomodulatory role attributed to steroid hormones, such as vitamin D₃ (VD₃) and 17β-estradiol (E₂), highlighted the importance of these hormones against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) infection. In order to understand their influence upon gene expression of immune and inflammatory responsive genes against <em>Mtb</em> we tested it <em>in vitro</em> using peripheral blood mononuclear cells (PBMCs). Cells were pretreated with VD₃ (50 ng/mL) or E₂ (100 nM/mL) and co-cultured with <em>H37Rv Mtb</em> or stimulated with lipopolysaccharide from <em>Escherichia coli</em> (LPS). After 24 h and 72 h of co-culture the <em>Mtb</em> viability in macrophages test was performed, as well the total RNA isolation for gene expression analysis by RT-qPCR of the following target genes: <em>NLRP3</em>, <em>DC-SIGN</em>, <em>IL-1β</em>, and <em>IL-10</em>. We also measured IL-10, TNF, IFN-γ, IL-4, IL-6, and IL-2 supernatant levels. As the main results, we found that VD₃ and E₂ downregulated the expression of inflammatory genes <em>NLRP3</em>, <em>IL-1β,</em> and <em>IL-10</em> expression in <em>Mtb</em> co-cultured cells. Finally, VD₃ treatment increased the release of the cytokine IFN-γ in <em>Mtb-</em>infected cells, while E₂ treatment inhibited the release of IL-10, TNF, IFN-γ, and IL-6. Therefore, we report an immunogenetic influence of VD₃ and E₂ upon <em>Mtb</em> co-culture.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102497"},"PeriodicalIF":3.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919976","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":"Analysis of T-lymphocyte subsets and risk factors in children with tuberculosis","authors":"Wei-Wei Ma ,&nbsp;Ling-Chao Wang ,&nbsp;De-An Zhao ,&nbsp;Na Wei ,&nbsp;Jun-Wei Cui ,&nbsp;Shu-Jun Li","doi":"10.1016/j.tube.2024.102496","DOIUrl":"10.1016/j.tube.2024.102496","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813–0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer–Lemeshow goodness-of-fit test showing consistent results (χ&lt;sup&gt;2&lt;/sup&gt; = 12.212, p = 0.142).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infecti","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102496"},"PeriodicalIF":3.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000222/pdfft?md5=d9f92cecb2ef90ab4b025bcead611fc8&pid=1-s2.0-S1472979224000222-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139920177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demonstrating the utility of the ex vivo murine mycobacterial growth inhibition assay (MGIA) for high-throughput screening of tuberculosis vaccine candidates against multiple Mycobacterium tuberculosis complex strains","authors":"Hannah Painter ,&nbsp;Sam Willcocks ,&nbsp;Andrea Zelmer ,&nbsp;Rajko Reljic ,&nbsp;Rachel Tanner ,&nbsp;Helen Fletcher","doi":"10.1016/j.tube.2024.102494","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102494","url":null,"abstract":"<div><p>Human tuberculosis (TB) is caused by various members of the <em>Mycobacterium tuberculosis</em> (Mtb) complex. Differences in host response to infection have been reported, illustrative of a need to evaluate efficacy of novel vaccine candidates against multiple strains in preclinical studies. We previously showed that the murine lung and spleen direct mycobacterial growth inhibition assay (MGIA) can be used to assess control of <em>ex vivo</em> mycobacterial growth by host cells. The number of mice required for the assay is significantly lower than <em>in vivo</em> studies, facilitating testing of multiple strains and/or the incorporation of other cellular analyses. Here, we provide proof-of-concept that the murine MGIA can be applied to evaluate vaccine-induced protection against multiple Mtb clinical isolates. Using an ancient and modern strain of the Mtb complex, we demonstrate that <em>ex vivo</em> bacillus Calmette–Guérin (BCG)-mediated mycobacterial growth inhibition recapitulates protection observed in the lung and spleen following <em>in vivo</em> infection of mice. Further, we provide the first report of cellular and transcriptional correlates of BCG-induced growth inhibition in the lung MGIA. The <em>ex vivo</em> MGIA represents a promising platform to gain early insight into vaccine performance against a collection of Mtb strains and improve preclinical evaluation of TB vaccine candidates.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102494"},"PeriodicalIF":3.2,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000209/pdfft?md5=3a411230d0757059acf5f7d8ee705a37&pid=1-s2.0-S1472979224000209-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caveolin-1 affects early mycobacterial infection and apoptosis in macrophages and mice","authors":"Yuqing Wu ,&nbsp;Andrea Riehle ,&nbsp;Barbara Pollmeier ,&nbsp;Stephanie Kadow ,&nbsp;Fabian Schumacher ,&nbsp;Marek Drab ,&nbsp;Burkhard Kleuser ,&nbsp;Erich Gulbins ,&nbsp;Heike Grassmé","doi":"10.1016/j.tube.2024.102493","DOIUrl":"10.1016/j.tube.2024.102493","url":null,"abstract":"<div><p>Tuberculosis, caused by <em>Mycobacterium tuberculosis</em>, remains one of the deadliest infections in humans. Because <em>Mycobacterium bovis</em> Bacillus Calmette-Guérin (BCG) share genetic similarities with <em>Mycobacterium tuberculosis</em>, it is often used as a model to elucidate the molecular mechanisms of more severe tuberculosis infection. Caveolin-1 has been implied in many physiological processes and diseases, but it's role in mycobacterial infections has barely been studied. We isolated macrophages from Wildtype or Caveolin-1 deficient mice and analyzed hallmarks of infection, such as internalization, induction of autophagy and apoptosis. For <em>in vivo</em> assays we intravenously injected mice with BCG and investigated tissues for bacterial load with colony-forming unit assays, bioactive lipids with mass spectrometry and changes of protein expressions by Western blotting. Our results revealed that Caveolin-1 was important for early killing of BCG infection <em>in vivo</em> and <em>in vitro</em>, controlled acid sphingomyelinase (Asm)-dependent ceramide formation, apoptosis and inflammatory cytokines upon infection with BCG. In accordance, Caveolin-1 deficient mice and macrophages showed higher bacterial burdens in the livers. The findings indicate that Caveolin-1 plays a role in infection of mice and murine macrophages with BCG, by controlling cellular apoptosis and inflammatory host response. These clues might be useful in the fight against tuberculosis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102493"},"PeriodicalIF":3.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000192/pdfft?md5=a28ccebedc8d781a4e2dfdaa37da06ff&pid=1-s2.0-S1472979224000192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139882544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmission of drug-resistant Mycobacterium tuberculosis isolates between Finnish- and foreign-born cases, 2014–2021: A molecular epidemiological study","authors":"Jiahui Zhu ,&nbsp;Marjo Haanpera ,&nbsp;Silja Mentula ,&nbsp;Olli Vapalahti ,&nbsp;Hanna Soini ,&nbsp;Tarja Sironen ,&nbsp;Ravi Kant ,&nbsp;Fathiah Zakham","doi":"10.1016/j.tube.2024.102492","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102492","url":null,"abstract":"<div><h3>Background</h3><p>Data on the molecular epidemiology and transmission of drug-resistant <em>Mycobacterium tuberculosis</em> (MTB) in low-incidence settings with immigration from high-incidence settings is limited.</p></div><div><h3>Method</h3><p>We included 115 drug-resistant (DR) MTB isolates with whole-genome sequencing data isolated in Finland between 2014 and 2021. Potential transmission clusters were identified using a threshold of 12 single-nucleotide polymorphisms (SNPs). Highly related clusters were identified using a threshold of 5 SNPs.</p></div><div><h3>Result</h3><p>Of the 115 DR MTB isolates, 31 (27.0%) isolates were from Finnish-born cases and 84 (73.0%) were from foreign-born cases. The proportion of multidrug-resistant (MDR) MTB isolates (30/84, 35.7%) from foreign-born cases was higher than that of MDR MTB isolates from Finnish-born cases (8/31, 25.8%). Lineage 2 (40/115, 34.8%) and lineage 4 (40/115, 34.8%) were the most prevalent lineages. A total of 25 (21.7%) isolates were classified into eight potential transmission clusters (≤12 SNPs). Furthermore, five highly related clusters (≤5 SNPs) were identified, including three DR MTB isolates from Finnish-born cases and 14 DR isolates from foreign-born cases.</p></div><div><h3>Conclusion</h3><p>The risk of DR MTB transmission between Finnish- and foreign-born persons is not negligible. Further research on clustering analysis in drug-susceptible MTB is worth to inform tuberculosis management and control in low-incidence settings with increasing immigration.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102492"},"PeriodicalIF":3.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000180/pdfft?md5=59447be64e2ef863c826da394eb7ac1e&pid=1-s2.0-S1472979224000180-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacies of three drug regimens containing omadacycline to treat Mycobacteroides abscessus disease","authors":"Binayak Rimal ,&nbsp;Chandra M. Panthi ,&nbsp;Yi Xie ,&nbsp;Daniel C. Belz ,&nbsp;Elisa H. Ignatius ,&nbsp;Christopher K. Lippincott ,&nbsp;Daniel H. Deck ,&nbsp;Alisa W. Serio ,&nbsp;Gyanu Lamichhane","doi":"10.1016/j.tube.2024.102482","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102482","url":null,"abstract":"<div><p><em>Mycobacteroides abscessus</em> (<em>Mab,</em> also known as <em>Mycobacterium abscessus</em>) causes opportunistic pulmonary and soft tissue infections that are difficult to cure with existing treatments. Omadacycline, a new tetracycline antibiotic, exhibits potent <em>in vitro</em> and <em>in vivo</em> activity against <em>Mab</em>. As regimens containing multiple antibiotics are required to produce a durable cure for <em>Mab</em> disease, we assessed efficacies of three three-drug combinations in a pre-clinical mouse model of pulmonary <em>Mab</em> disease to identify companion drugs with which omadacycline exhibits the highest efficacy. Additionally, we assessed the susceptibility of <em>Mab</em> recovered from mouse lungs after four weeks of exposure to the three triple-drug regimens. Among the three-drug regimens, omadacycline + imipenem + amikacin produced the largest reduction in <em>Mab</em> burden, whereas omadacycline + imipenem + linezolid exhibited the most effective early bactericidal activity. Omadacycline + linezolid + clofazimine, a regimen that can be administered orally, lacked early bactericidal activity but produced a gradual reduction in the lung <em>Mab</em> burden over time. The robust efficacy exhibited by these three regimens in the mouse model supports their further evaluation in patients with <em>Mab</em> lung disease. As we were unable to isolate drug-resistant <em>Mab</em> mutants at the completion of four weeks of treatment, these triple-drug combinations show promise of producing durable cure and minimizing selection of resistant mutants.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102482"},"PeriodicalIF":3.2,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000088/pdfft?md5=386b6f32525281577510225b87d29728&pid=1-s2.0-S1472979224000088-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}