Tuberculosis最新文献

{"title":"Development of tetracycline analogues with increased aqueous stability for the treatment of mycobacterial infections","authors":"Jiuyu Liu ,&nbsp;Gregory A. Phelps ,&nbsp;Christine M. Dunn ,&nbsp;Patricia A. Murphy ,&nbsp;Laura A. Wilt ,&nbsp;Victoria Loudon ,&nbsp;Robin B. Lee ,&nbsp;Dinesh Fernando ,&nbsp;Lei Yang ,&nbsp;Kristina N. Tran ,&nbsp;Brennen T. Troyer ,&nbsp;Andres Obregon-Henao ,&nbsp;Richard E. Lee","doi":"10.1016/j.tube.2024.102592","DOIUrl":"10.1016/j.tube.2024.102592","url":null,"abstract":"<div><div>Tetracycline analogs from the minocycline family have recently shown promise for the treatment of non-tuberculous mycobacterial infections. However, current tetracycline and minocycline therapeutics can be limited by tolerability, stability, or inactivation by TetX. In this study, a series of novel 9-heteroaryl substituted minocycline analogs were designed and synthesized, which resulted in analogs with good <em>in vitro</em> activity against <em>Mycobacterium tuberculosis</em> and <em>Mycobacterium abscessus</em>, stability in water for more than 7 days, avoidance of TetX inactivation in <em>M. abscessus,</em> and a lack of cytotoxicity in HepG2 mammalian cells. In vivo efficacy was confirmed for the tetracycline analogs in an acute model of GM-CSF KO mice infected with <em>M. abscessus</em>, displaying superior efficacy to standard-of-care antibiotic clarithromycin. Molecular modeling and potentiation assays demonstrate avoidance of MabTetX, and the structure-activity relationships of the series are discussed herein for <em>M</em>. <em>tuberculosis</em> and <em>M</em>. <em>abscessus</em>.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102592"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872894","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":"Utility of pleural fluid-derived extracellular vesicles as a source of Mycobacterium tuberculosis antigens MPT51 and MPT64 for pleural TB diagnosis: a proof-of-concept study","authors":"Neha Jindal ,&nbsp;Pratibha Sharma ,&nbsp;Sachin Punia ,&nbsp;Manisha Dass ,&nbsp;Divya Anthwal ,&nbsp;Rakesh Kumar Gupta ,&nbsp;Manpreet Bhalla ,&nbsp;Ritu Singhal ,&nbsp;Ashish Behera ,&nbsp;Rakesh Yadav ,&nbsp;Sunil Sethi ,&nbsp;Sahajal Dhooria ,&nbsp;Ashutosh Nath Aggarwal ,&nbsp;Sagarika Haldar","doi":"10.1016/j.tube.2024.102578","DOIUrl":"10.1016/j.tube.2024.102578","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have recently emerged as a source of microbe-specific biomarkers for disease diagnosis. In the present study, we evaluated the utility of pleural fluid-derived extracellular vesicles (pEVs) as a source of <em>Mycobacterium tuberculosis</em> (<em>M</em>. <em>tb</em>.) antigens for pleural TB (pTB) diagnosis. EVs were isolated from pleural fluid (PF) samples and were characterized by scanning electron microscopy, and immunoblotting by targeting CD63 and LAMP2 markers. Antigen-detection ELISAs were developed for 2 <em>M</em><em>.</em> <em>tb</em><em>.</em>-specific antigens, MPT51 and MPT64 in pEVs (pEV-ELISA) and direct PF samples (PF-ELISA), and were evaluated on n = 86 samples in a blinded manner. Cut-off values were calculated by ROC-curve analysis to achieve 90 % (95%CI:73.47–97.89) and 86.67 % (95%CI:69.28–96.24) specificity for MPT51 and MPT64 pEV-ELISA respectively. The sensitivity of pEV-ELISA was 71.43 % (95%CI; 29.04–96.33) for MPT51 antigen and 57.14 % (95%CI; 18.41–90.1) for MPT64 antigen in the ‘Definite’ pTB group, while in the ‘Definite and Probable’ pTB group, the sensitivity was 62.86 % (95%CI:44.92–78.53) for MPT51 and 65.71 % (95%CI:47.79–80.87) for MPT64. The performance of PF-ELISA was sub-optimal, with 28.57 % (95%CI:3.67–70.96) and 14.29 % (95%CI:0.36–57.87) sensitivity for MPT51 and MPT64 in ‘Definite’ pTB group respectively. We conclude that <em>M</em>. <em>tb</em>.-antigens are concentrated in the EV-fraction of PF samples and EVs can be utilized for antigen-detection assays for pTB diagnosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102578"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795232","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":"A survey of physicians, biomedical researchers and college-educated adults in urban north India about inhaled therapies","authors":"Khushboo Verma ,&nbsp;Amit Misra","doi":"10.1016/j.tube.2024.102591","DOIUrl":"10.1016/j.tube.2024.102591","url":null,"abstract":"<div><div>We surveyed 15 persons with a medical qualification, 133 graduate students doing biomedical research and 56 students or working people with a college education in any discipline. Questions were designed to gauge awareness about inhaled therapies for tuberculosis (TB), non-tubercular mycobacterial lung disease (NTM-LD) and idiopathic pulmonary fibrosis (IPF). Respondents from six cities in North India, aged between 21 and 57 years answered 20 questions. All physicians, 99.25 % of graduate students and 85.71 % of the rest were aware and positive about inhalations for asthma, but these proportions fell to 69.92 and 66.07 in respect of other diseases. All respondents in the first two categories agreed that it was easy to train patients in the use of inhalation devices, while the third group was unanimous that there would be no aversion to using inhalation devices. A question asking whether the respondent would prescribe or opt for inhaled therapies for own use elicited an affirmative answer only from 40.00 % of physicians, 43.61 % of researchers and 23.21 % of college-educated persons (overall: 37.56 %). We concluded that inhaled therapies for diseases other than asthma are not well known and find limited acceptance among the populations sampled.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102591"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872939","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":"Analogue of the natural product ecumicin causes sustained growth inhibition of Mycobacterium tuberculosis under multiple growth conditions","authors":"Maxwell T. Stevens ,&nbsp;Paige M.E. Hawkins ,&nbsp;Trixie Wang ,&nbsp;Richard J. Payne ,&nbsp;Warwick J. Britton","doi":"10.1016/j.tube.2024.102594","DOIUrl":"10.1016/j.tube.2024.102594","url":null,"abstract":"<div><div>Multi-drug-resistant <em>Mycobacterium tuberculosis</em> is an escalating global health problem, and a strong pipeline of novel compounds is needed to combat rising antimicrobial resistance. Ecumicin is a novel analogue of the natural antimycobacterial cyclic peptide ecumicin, with selective activity against <em>Mycobacterium</em> species. The activity of ecumicin∗ was compared to that of frontline tuberculosis therapies under <em>in vitro</em> conditions representative of niches where <em>M. tuberculosis</em> resides in the human lung. <em>M. tuberculosis</em> expressing luciferase was cultured in defined 7H9-based media containing glucose, butyrate, valerate, acidified glucose, low or high cholesterol concentrations, or intracellularly in human THP-1 and mouse RAW264.7 macrophages. Ecumicin∗ effectively killed <em>M. tuberculosis</em> under all assay conditions. The IC₉₀ of ecumicin∗ was increased in acidified 7H9 media, and both IC₉₀ and AUC₉₀ values were increased in valerate, cholesterol, high cholesterol culture media. In time-kill assays, <em>anti</em>-<em>M. tuberculosis</em> activity of ecumicin∗ was sustained for 28 days. By comparison, IC₅₀ and IC₉₀ of isoniazid were decreased in butyrate and cholesterols medias, and mycobacterial regrowth occurred in glucose and cholesterol culture medias within 14 days at high isoniazid concentrations. Ecumicin∗ inhibited <em>M. tuberculosis</em> growth in THP-1 macrophages, and at higher IC₉₀ in mouse RAW264.7 macrophages. Drug testing under disease-relevant conditions is important prior to <em>in vivo</em> examination, and ecumicin∗ has proven effective in multiple <em>in vitro</em> conditions typical of the lung environment of tuberculosis patients.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102594"},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932802","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":"Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy","authors":"Petter Holmberg ,&nbsp;Martina Janoušková ,&nbsp;Tobias Schmidt ,&nbsp;Ariane Neumann ,&nbsp;Oskar Olsson ,&nbsp;Per-Erik Isberg ,&nbsp;Maja Reimann ,&nbsp;Kristian Riesbeck ,&nbsp;Sten Skogmar ,&nbsp;Per Björkman","doi":"10.1016/j.tube.2024.102595","DOIUrl":"10.1016/j.tube.2024.102595","url":null,"abstract":"<div><h3>Background</h3><div>Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT).</div></div><div><h3>Methods</h3><div>Individuals with likelihood of recent Mtb exposure, aged 15–25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included. Persons with TBI were sampled prior to TPT (IGRA + pre-treatment, <em>n</em> = 15) or after completion of TPT (IGRA + post-treatment, <em>n</em> = 15). Five persons without TBI were included as controls (IGRA-). Levels of 40 mediators related to TB immune control in blood incubated with Mtb antigens in the QuantiFERON-TB Plus® kit were assessed with electrochemiluminescence assay and compared between participant categories.</div></div><div><h3>Results</h3><div>The concentration of 10 mediators (GM-CSF, interferon-γ, IL-2, I-TAC, IL-12, IP-10, I-309, MCP-2, MIG, and VEGF) significantly differed between IGRA + pre-treatment and IGRA-. A non-significant trend in levels of these markers was observed between IGRA + pre-treatment, IGRA + post-treatment and IGRA-. Based on these mediators two clusters were identified: A (<em>n</em> = 16), including 5 IGRA-, 4 IGRA + pre-treatment, 7 IGRA + post-treatment and B (<em>n</em> = 19), including 11 IGRA + pre-treatment and 8 IGRA + post-treatment.</div></div><div><h3>Conclusion</h3><div>Plasma levels of several Mtb-triggered mediators differed with regard to TBI status among persons recently exposed to TB, suggesting the potential for alternative markers to assess TBI status. Longitudinal analysis of these mediators during TPT is warranted to explore whether these markers can be used to assess likelihood of persistence of viable bacilli in Mtb-exposed individuals.</div><div>ClinicalTrials.govID:NCT05621343.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102595"},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915599","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":"Prevalence of BCG scar among vaccinated children and its correlation with Mantoux skin test at Omdawanban area, Sudan","authors":"Sabir Awad Mustafa","doi":"10.1016/j.tube.2024.102596","DOIUrl":"10.1016/j.tube.2024.102596","url":null,"abstract":"<div><h3>Purpose</h3><div>Tuberculosis (TB) remains a significant public health concern globally. Bacille Calmette-Guérin (BCG) vaccination is widely used, but scar formation post-vaccination is not universal, which raises concerns about its efficacy. The Mantoux test is used to assess the immune response following BCG vaccination. This study aims to evaluate the prevalence of BCG scar formation among vaccinated children and its correlation with Mantoux test reactions.</div></div><div><h3>Methods</h3><div>This quantitative, cross-sectional descriptive study was conducted among children aged 3 months to 9 years at the vaccination office in Omdawanban, Sudan, from September to October 2021. Data were collected using structured surveys and the Mantoux skin test.</div></div><div><h3>Results</h3><div>Out of 350 vaccinated children, 285 (81.4 %) exhibited a visible BCG scar, while 65 (18.6 %) did not. Mantoux test positivity was observed in 132 children (37.7 %). A significant association was found between the presence of a BCG scar and a positive Mantoux test result (p &lt; 0.05), with 39.3 % of children with a visible scar showing positive Mantoux results compared to 30.8 % of children without a scar. The likelihood of a positive Mantoux test was 3.2 times higher in children with a visible BCG scar (OR = 3.2, 95 % CI [1.8–5.8]). Mantoux positivity also varied by age, with the highest rate (41.2 %) observed among children aged 5–9 years (p = 0.03).</div></div><div><h3>Conclusions</h3><div>There is a significant association between BCG scar formation and Mantoux test positivity. Improved training for healthcare workers and better education for mothers about vaccination are recommended.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"151 ","pages":"Article 102596"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915617","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":"Impaired control of Mycobacterium tuberculosis infection in mast cell-deficient KitW-sh/W−sh mice","authors":"Berenice Villareal-Rivota ,&nbsp;Yatsiri G. Meneses-Preza ,&nbsp;Marcia Campillo-Navarro ,&nbsp;Bibiana Patricia Ruiz-Sánchez ,&nbsp;Rodolfo Soria-Castro ,&nbsp;Jorge Barrios-Payán ,&nbsp;Dulce Mata-Espinosa ,&nbsp;Luis Donis-Maturano ,&nbsp;Sonia M. Pérez-Tapia ,&nbsp;Alma D. Chávez-Blanco ,&nbsp;Sergio Estrada-Parra ,&nbsp;Rogelio Hernández-Pando ,&nbsp;Rommel Chacón-Salinas","doi":"10.1016/j.tube.2024.102587","DOIUrl":"10.1016/j.tube.2024.102587","url":null,"abstract":"<div><div>Tuberculosis (TB) is a global health problem with diverse clinical manifestations. Different cells of the immune response participate in containing the infection, mainly through the development of granulomas. Mast cells (MCs) are hematopoietic cells that participate in the immune response to different pathogens, and <em>in vitro</em> evidence indicates that they can be activated by <em>Mycobacterium tuberculosis</em> (Mtb). The aim of this study was to evaluate the role of MCs in a murine TB model. We observed that Kit^W-sh/W−sh mast cell-deficient mice showed increased bacterial load in the lungs and the spleen compared to wild-type C57BL/6 mice. Furthermore, MC-deficient mice showed fewer pulmonary granulomas but an early higher inflammatory infiltrate. Interestingly, serum cytokine levels were altered in MC-deficient mice, which showed increased levels of IL-4, IL-5, and IL-22 during the early phase of the infection but increased levels of IFN-γ, IL-9, IL-10, and IL-21 during the late phase of the infection. These results show that mast cells play an important role during Mtb infection by modulating the immune response to the bacteria.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102587"},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745212","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":"Identification of BMVC-8C3O as a novel Pks13 inhibitor with anti-tuberculosis activity","authors":"Tianjun Liu ,&nbsp;Jianzhou Meng ,&nbsp;Bin Wang ,&nbsp;Xiaohui Li ,&nbsp;Qian Wang ,&nbsp;Sihan Liu ,&nbsp;Yan Guan ,&nbsp;Xiao Wang ,&nbsp;Yishuang Liu","doi":"10.1016/j.tube.2024.102579","DOIUrl":"10.1016/j.tube.2024.102579","url":null,"abstract":"<div><div>Given the increasing prevalence of drug-resistant tuberculosis (TB), there is an urgent demand in developing novel anti-TB medications with highly effective, safe, and utilize innovative mechanisms of action. Blocking the mycolic acid synthesis pathway is well-established to be a significant strategy in developing anti-TB drugs, and Pks13 was identified as a crucial enzyme in this process. Importantly, the modes of action of recognized Pks13 inhibitors differ from traditional anti-TB medications, highlighting Pks13 as a potential and promising target in drug development within TB treatment. In this study, we discovered a compound named BMVC-8C3O that effectively inhibited the activity of Pks13 with a 6.94 μM IC₅₀ value. The binding between BMVC-8C3O and Pks13 was validated through surface plasmon resonance (SPR) assay as well as molecular docking analysis. Moreover, the SPR assay showed that the mutation of Asn1640 and Ser1533 resulted in decreased affinity of BMVC-8C3O to Pks13. Additionally, BMVC-8C3O not only exhibited activity against <em>Mycobacterium tuberculosis</em> (MTB), but also displayed potential intracellular anti-TB activity in macrophages. In summary, our findings indicate that BMVC-8C3O holds great potential as a lead compound against TB.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"150 ","pages":"Article 102579"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695830","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":"Altered intestinal microbiota and fecal metabolites in patients with latent and active pulmonary tuberculosis","authors":"Hua Zhang ,&nbsp;Mengjiao Xue ,&nbsp;Xinxin He ,&nbsp;Lifang Sun ,&nbsp;Qiang He ,&nbsp;Yunguang Wang ,&nbsp;Juan Jin","doi":"10.1016/j.tube.2024.102577","DOIUrl":"10.1016/j.tube.2024.102577","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear.</div></div><div><h3>Methods</h3><div>Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups.</div></div><div><h3>Results</h3><div>Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids.</div></div><div><h3>Conclusions</h3><div>we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102577"},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644841","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":"Functional impact of a deletion in Mycobacterium bovis BCG Moreau celA1 gene","authors":"Leonardo Henrique Ferreira Gomes ,&nbsp;Paloma Rezende Corrêa,&nbsp;Marcos Gustavo Araujo Schwarz,&nbsp;Leila Mendonça-Lima","doi":"10.1016/j.tube.2024.102576","DOIUrl":"10.1016/j.tube.2024.102576","url":null,"abstract":"<div><div>Several mycobacterial species are known to cause human diseases, such as tuberculosis and leprosy. In addition to these pathogenic species, there are also saprophytic representatives, which occasionally cause opportunistic infections. It is well established that numerous mycobacteria produce biofilms containing cellulose, and their genomes frequently harbor genes involved in cellulose degradation, such as <em>celA1</em>. Notably, the BCG Moreau vaccine strain carries a specific deletion of two-base pairs, resulting in a predicted protein with fewer than 100 amino acids in the catalytic portion at the C-terminal end. We investigated the functional consequences of this polymorphism and observed that recombinant enzyme from the Moreau strain lack catalytic activity. Furthermore, compared to the Pasteur strain, Moreau is unable to utilize carboxymethylcellulose (CMC) as the sole carbon source. These findings suggest an absence of cellulolytic activity in this strain, which may influence the bacterium virulence.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102576"},"PeriodicalIF":2.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640034","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}