Tuberculosis最新文献_第2页

Chasing the “White Plague” in the Barbaricum of the Carpathian Basin – A case with tuberculous meningitis discovered in a Sarmatian-period (2nd–3rd-century-CE) storage pit from the archaeological site of Kiskundorozsma–Daruhalom-dűlő II (Hungary) 在喀尔巴阡盆地的野蛮地区追逐“白色瘟疫”——在匈牙利Kiskundorozsma-Daruhalom-dűlő II考古遗址的一个萨尔马提亚时期（公元2 - 3世纪）的储存坑中发现的一例结核性脑膜炎病例

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-12 DOI: 10.1016/j.tube.2025.102632

Ágota Madai , Marcos De Andrés Montero , Luca Kis , Csaba Szalontai , Anna Szigeti , István Major , Attila Kiss P. , Olga Spekker

{"title":"Chasing the “White Plague” in the Barbaricum of the Carpathian Basin – A case with tuberculous meningitis discovered in a Sarmatian-period (2nd–3rd-century-CE) storage pit from the archaeological site of Kiskundorozsma–Daruhalom-dűlő II (Hungary)","authors":"Ágota Madai , Marcos De Andrés Montero , Luca Kis , Csaba Szalontai , Anna Szigeti , István Major , Attila Kiss P. , Olga Spekker","doi":"10.1016/j.tube.2025.102632","DOIUrl":"10.1016/j.tube.2025.102632","url":null,"abstract":"<div><div>The aim of our paper is to demonstrate a case (<strong>KD429</strong>) with tuberculous meningitis (TBM) from the 2nd–3rd‒century‒CE Carpathian Basin. The skeleton of <strong>KD429</strong> was subject to a detailed macromorphological evaluation, focusing on the detection of pathological lesions likely related to tuberculosis (TB). It was the presence of endocranial alterations, especially the TB-specific granular impressions, based on which the diagnosis of TBM was established in <strong>KD429</strong>. Besides <strong>KD429</strong>, only eight cases with TB have been published from the Sarmatian-period (1st–5th centuries CE) Carpathian Basin. Reports of archaeological cases with TB, like <strong>KD429</strong>, can provide invaluable information about the spatio-temporal distribution of the disease in the past. Nonetheless, to get a more accurate picture about the burden that TB may have put on the Sarmatians, the systematic macromorphological (re-)evaluation of their osteoarchaeological series would be advantageous. Interestingly, the skeleton of <strong>KD429</strong> was unearthed from not a grave-pit but a storage pit from the archaeological site of Kiskundorozsma–Daruhalom-dűlő II (Hungary). At the current state of research, the motive behind the exclusion of <strong>KD429</strong> from the “normal” burial custom cannot be determined; therefore, it remains an open question whether their disease (TBM) played a role in it or not.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102632"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628521","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}

引用次数: 0

Dry powder Inhalation of lytic mycobacteriophages for adjunct therapy in a mouse model of infection with Mycobacterium tuberculosis 干粉吸入溶解性分枝杆菌噬菌体辅助治疗结核分枝杆菌感染小鼠模型

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-11 DOI: 10.1016/j.tube.2025.102631

Sunil K. Raman , Trisha Roy , Khushboo Verma , Chunna Yadav , Sonia Verma , Venkata Siva Reddy Deivreddy , Hasham Shafi Sofi , Reena Bharti , Rahul Sharma , Himanshu Bansode , Akhilesh Kumar , Rakesh Kumar Sharma , Jyotsna Singh , Madhav N. Mugale , Urmi Bajpai , Vikas Jain , Amit Kumar Singh , Amit Misra

{"title":"Dry powder Inhalation of lytic mycobacteriophages for adjunct therapy in a mouse model of infection with Mycobacterium tuberculosis","authors":"Sunil K. Raman , Trisha Roy , Khushboo Verma , Chunna Yadav , Sonia Verma , Venkata Siva Reddy Deivreddy , Hasham Shafi Sofi , Reena Bharti , Rahul Sharma , Himanshu Bansode , Akhilesh Kumar , Rakesh Kumar Sharma , Jyotsna Singh , Madhav N. Mugale , Urmi Bajpai , Vikas Jain , Amit Kumar Singh , Amit Misra","doi":"10.1016/j.tube.2025.102631","DOIUrl":"10.1016/j.tube.2025.102631","url":null,"abstract":"<div><div>Inhaled therapy of tuberculosis (TB) by a Dry Powder Inhalation (DPI) comprising mycobacteriophage D29 and TM4 was non-inferior to oral anti-tuberculosis therapy (ATT) with isoniazid and rifampicin in a mouse model of infection with <em>Mycobacterium tuberculosis</em> (Mtb). No pharmaceutical phage product of mycobacteriophages is approved for large-scale production. We scaled up preparation and downstream processing of phages, developed DPI formulations, and established methods for determining identity, purity, assay, stability, and critical quality attributes (CQA). We carried out cell-based assays of intracellular bactericidal activity and pharmacokinetics and comparative efficacy in Mtb-infected mice. Daily doses of the DPI containing ∼10<sup>10</sup> Plaque Forming Units/dose DPI reduced Mtb colony forming units (CFU) in the lungs from 6.4 ± 0.3-log to 4.8 ± 0.7-log in four weeks, while oral human equivalent doses (HED) of isoniazid and rifampicin reduced CFU to 3.8 ± 0.8-log. Combining inhaled phages with oral drugs sterilized the lungs of one of four mice and reduced group mean CFU to 2.3-log. Inhalations significantly upregulated tumor necrosis factor (TNF) in lung tissue to ∼1500 pg/ml of homogenate, improved organ morphology, and reduced histopathology. The HD DPI may be a useful adjunct to oral drugs. Dose-finding animal efficacy studies are required before assessing preclinical safety.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102631"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628522","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}

引用次数: 0

A snapshot of genomic diversity and transmission clusters of rifampin-resistant Mycobacterium tuberculosis complex in the Central African Republic 中非共和国耐利福平结核分枝杆菌复合体基因组多样性和传播集群的快照

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-07 DOI: 10.1016/j.tube.2025.102627

B. Jolly , J. Saad , A. Farra , A. Manirakiza , G. Zandanga , E. Nakoune , Y. Boum II , E. Gando , G. Grine , C. Mossoro-Kpinde , M. Drancourt

{"title":"A snapshot of genomic diversity and transmission clusters of rifampin-resistant Mycobacterium tuberculosis complex in the Central African Republic","authors":"B. Jolly , J. Saad , A. Farra , A. Manirakiza , G. Zandanga , E. Nakoune , Y. Boum II , E. Gando , G. Grine , C. Mossoro-Kpinde , M. Drancourt","doi":"10.1016/j.tube.2025.102627","DOIUrl":"10.1016/j.tube.2025.102627","url":null,"abstract":"<div><div>Tuberculosis, a significant public health concern in Central African Republic lacks whole-genome-based identification and typing of the <em>Mycobacterium tuberculosis</em> complex strains circulating in populations in that country. Here, we investigated 68 rifampin-resistant clinical isolates collected in 2024 from eight districts in Bangui and surrounding regions. The analysis revealed that all isolates were <em>M. tuberculosis stricto sensu</em>, distributed across nine lineages: L4.1.2.1 Haarlem (n = 20), L4.6 Euro-American (n = 17), L4.6.1.2 Uganda (n = 13), L4.6.2.2 Cameroon (n = 12), and L4.1.1.1 X-Type (n = 2), and single isolates in L4.1 (Euro-American), L4.6.1 (Uganda), L4.3.1 (LAM), and L3 (Delhi-CAS). The antibiotic resistance profile showed that 9/68 (13.2 %) of the <em>M. tuberculosis</em> isolates were susceptible, while 59/68 (86.7 %) exhibited at least one predicted antibiotic resistance. These data provide new insights into tuberculosis transmission in Central African Republic in contrast to reports from neighboring countries, including the absence of <em>Mycobacterium bovis</em>, hence zoonotic tuberculosis and other factors. This preliminary study limited to rifampin-resistant isolates, nevertheless paves the way for a genome-based survey of tuberculosis in Central African Republic which is essential for enhancing the management and control of the deadly tuberculosis that is a public health concern in the country.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102627"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609263","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}

引用次数: 0

Integrative exploration of 2-phenylquinolin-4(1H)-one tethered 1,2,3-triazole derivatives: A comprehensive in vitro and in silico investigation towards novel anti-tubercular agents 2-苯基喹啉-4(1H)- 1系链1,2,3-三唑衍生物的综合探索：新型抗结核药物的体外和体内综合研究

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-07 DOI: 10.1016/j.tube.2025.102628

Raut Mehavi , Walhekar Vinayak , Patil Ashwini , Pavan Kumar Jaini , Mohana Vamsi Nuli , Bhikshapathi DVRN , Ravindra Kulkarni

{"title":"Integrative exploration of 2-phenylquinolin-4(1H)-one tethered 1,2,3-triazole derivatives: A comprehensive in vitro and in silico investigation towards novel anti-tubercular agents","authors":"Raut Mehavi , Walhekar Vinayak , Patil Ashwini , Pavan Kumar Jaini , Mohana Vamsi Nuli , Bhikshapathi DVRN , Ravindra Kulkarni","doi":"10.1016/j.tube.2025.102628","DOIUrl":"10.1016/j.tube.2025.102628","url":null,"abstract":"<div><div>Novel 2-phenylquinolin-4(1<em>H</em>)-one threaded 1,2,3- triazoles were designed, synthesized and evaluated for <em>in vitro</em> activity against <em>Mycobacterium tuberculosis</em> which could be putatively through inhibition of carbonic anhydrase <em>β</em>. Molecules were synthesized in simple Schottan Baumann reaction for amide synthesis. Purified compounds were screened for antitubercular and antibacterial activities. Among them, 1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-phenylquinolin-4(1<em>H</em>)-one <strong>9j</strong> with 2-methoxy at the ortho position of phenyl ring indicated significant antitubercular activity with MIC value of <strong>6.25, 3.12</strong> and <strong>3.12 μg/ml</strong> antimicrobial activity against <em>Mycobacterium tuberculosis,</em> gram positive and gram negative strain. The molecular docking and dynamics studies demonstrated that the compound <strong>9j</strong> occupied the Zn-binding site of the enzyme with docking energy of <strong>-6.2 kcal mol<sup>−1</sup></strong>. <em>In silico</em> ADME studies indicated that the synthesized compounds have good drug likeliness. The findings explore and present a potential series of antimycobacterial agents in the hope of developing new and advanced therapeutics for tuberculosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102628"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619972","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}

引用次数: 0

An immunocompetent rat model of Mycobacterium abscessus multinodular granulomatous lung infection 脓肿分枝杆菌多结节性肉芽肿性肺感染免疫活性大鼠模型

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-04 DOI: 10.1016/j.tube.2025.102629

Sholeh Feizi , Clare M. Cooksley , Nicole Reyne , Bernadette Boog , John Finnie , Gohar Shaghayegh , Karen Hon , Mahnaz Ramezanpour , Alkis J. Psaltis , Peter-John Wormald , Patricia Cmielewski , Alexandra McCarron , Martin Donnelley , David Parsons , Sarah Vreugde

{"title":"An immunocompetent rat model of Mycobacterium abscessus multinodular granulomatous lung infection","authors":"Sholeh Feizi , Clare M. Cooksley , Nicole Reyne , Bernadette Boog , John Finnie , Gohar Shaghayegh , Karen Hon , Mahnaz Ramezanpour , Alkis J. Psaltis , Peter-John Wormald , Patricia Cmielewski , Alexandra McCarron , Martin Donnelley , David Parsons , Sarah Vreugde","doi":"10.1016/j.tube.2025.102629","DOIUrl":"10.1016/j.tube.2025.102629","url":null,"abstract":"<div><div>Animal models that can mimic progressive granulomatous pulmonary disease (PD) due to non-tuberculous mycobacteria (NTM) have not been established in rats to date. These models could assist with the study of the pathophysiology of NTM-PD as well as the preclinical development of new therapies. In the present study, an immunocompetent rat model of progressive <em>Mycobacterium abscessus (MABs)</em>- PD was developed using <em>MABs</em> originating from a patient with cystic fibrosis. <em>MABs</em> was embedded in agarose beads and delivered intratracheally to the lungs of Sprague Dawley rats two times at a one-week time interval. The bacterial burden of lysed lungs, spleen and liver was assessed by calculating colony forming units (CFUs) on day 28. Lung CFUs indicated a ∼1.2–2 log<sub>10</sub> total CFU increase compared to the initial total bacterial load instilled into the lungs. In all infected rats, multinodular granulomatous inflammatory lesions containing <em>MABs</em> were found in the lung. These findings support the establishment of an immunocompetent <em>MABs</em> PD rat model, characterised by an increase in mycobacterial burden over time and a chronic granulomatous inflammatory response to the <em>MABs</em> infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102629"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562533","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}

引用次数: 0

The evaluation of Phenylalanine-tRNA ligase beta unit (PheT), as a potential target in Mycobacterium abscessus 苯丙氨酸- trna连接酶β单元（PheT）作为脓肿分枝杆菌潜在靶点的评价

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-03-01 DOI: 10.1016/j.tube.2025.102626

Weile Xie , Dan Luo , Mingqing Wu , Yicheng Sun , Zhe Wang

{"title":"The evaluation of Phenylalanine-tRNA ligase beta unit (PheT), as a potential target in Mycobacterium abscessus","authors":"Weile Xie , Dan Luo , Mingqing Wu , Yicheng Sun , Zhe Wang","doi":"10.1016/j.tube.2025.102626","DOIUrl":"10.1016/j.tube.2025.102626","url":null,"abstract":"<div><div><em>Mycobacterium abscessus</em> (<em>M. abscessus</em>) is an emerging pathogenic mycobacterium that mainly causes pulmonary infections, especially in immunocompromised patients. This bacterium shows exhibits intrinsic resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and clinicians, thereby raising the need for innovative drug discovery. In this study, we selected phenylalanine-tRNA ligase beta unit (<em>PheT</em>) as a model target and used CRISPR interference to evaluate its essentiality as a therapeutic target against <em>M. abscessus</em>. The results show that genetically disruption of <em>PheT</em> leads to clear growth inhibitory phenotypes both <em>in vitro</em> and <em>in vivo</em>. Further transcriptome analysis revealed differential expression of host genes in response to <em>PheT</em> gene silencing, including genes involved in the cell cycle, apoptotic signaling, and inflammatory responses. Overall, <em>PheT</em> gene plays a crucial role in <em>M. abscessus</em> infection, and its silencing may represent a druggable therapeutic strategy for treating this infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102626"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534828","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}

引用次数: 0

A novel method for detecting Lipoarabinomannan in urine with the promise of meeting the WHO target product profile for the diagnosis of tuberculosis 一种检测尿液中脂arabinman聚糖的新方法，有望满足世卫组织诊断结核病的目标产品概况

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-02-24 DOI: 10.1016/j.tube.2025.102619

Katharina Budde , Christoph Lange , Maja Reimann , Nika Zielinski , Lennard Meiwes , Niklas Köhler

{"title":"A novel method for detecting Lipoarabinomannan in urine with the promise of meeting the WHO target product profile for the diagnosis of tuberculosis","authors":"Katharina Budde , Christoph Lange , Maja Reimann , Nika Zielinski , Lennard Meiwes , Niklas Köhler","doi":"10.1016/j.tube.2025.102619","DOIUrl":"10.1016/j.tube.2025.102619","url":null,"abstract":"<div><div>The diagnosis of tuberculosis largely relies on the detection of <em>Mycobacterium tuberculosis (M. tuberculosis)</em> via pathogen-specific DNA or bacterial culture from sputum samples. As the only point-of-care test so far, urinary lipoarabinomannan (LAM) has been endorsed by the World Health Organization for the diagnosis of tuberculosis in people living with HIV.</div><div>In this study, the electrochemiluminescence LAM research assay (EclLAM) was used to measure LAM in the urine of HIV-sero-negative individuals with pulmonary tuberculosis and to monitor anti-tuberculosis treatment. Urine samples from 18 patients with microbiologically confirmed tuberculosis were analyzed before and after the initiation of anti-tuberculosis therapy and 17 healthy controls via the S4-20/A194-01 antibody pair.</div><div>The assay identified 13/18 (72.2 %) patients with tuberculosis and was negative in 17/17 (100.0 %) controls (AUC 0.88). The results of the reactive urine LAM tests correlated with the detection of <em>M. tuberculosis</em> growth in culture (r = 0.94, p < 0.05).</div><div>In conclusion, the LAM-specific antibody assay is promising to fulfill the WHO target product profile for the diagnosis of tuberculosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102619"},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552987","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}

引用次数: 0

Rv3371, a triacylglycerol synthase promotes survival of Mycobacterium tuberculosis in the host through its contributions to redox homeostasis and propionate detoxification Rv3371是一种三酰基甘油合成酶，它通过氧化还原稳态和丙酸解毒促进宿主结核分枝杆菌的存活

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-02-21 DOI: 10.1016/j.tube.2025.102617

Rahul Kumar Maurya , Sarah Fatima , Swati Anand , Rajmani Raju , Suman Bharti , Shivangi Rastogi , Umamageswaran Venugopal , Amitava Sinha , Amit Singh , Manju Y. Krishnan

{"title":"Rv3371, a triacylglycerol synthase promotes survival of Mycobacterium tuberculosis in the host through its contributions to redox homeostasis and propionate detoxification","authors":"Rahul Kumar Maurya , Sarah Fatima , Swati Anand , Rajmani Raju , Suman Bharti , Shivangi Rastogi , Umamageswaran Venugopal , Amitava Sinha , Amit Singh , Manju Y. Krishnan","doi":"10.1016/j.tube.2025.102617","DOIUrl":"10.1016/j.tube.2025.102617","url":null,"abstract":"<div><div>Triacylglycerol (TAG) is the major storage lipid of mycobacteria. <em>Mycobacterium tuberculosis</em> (Mtb) genome encodes 15 triacylglycerol synthases (Tgs), which are speculated to differ in substrate preference, suggesting specific physiological roles. In this study, we investigated the role of a Tgs, Rv3371, in the context of infection. <em>Rv3371</em> knock-out (KO) Mtb was attenuated in mice, with corresponding poor fitness inside macrophages. The KO was more sensitive to free long-chain fatty acids, but was more tolerant to oxidative and nitrosative stresses. Enzyme kinetics of Rv3371 showed its preference for propionyl-CoA. Excess propionate in growth medium retarded the growth of the KO more significantly than the wild type and complemented mutant. This suggests an additional role of Rv3371 in reducing toxic levels of propionate in Mtb by synthesising propionyl TAG. Moreover, chemical inhibition of methylcitrate cycle caused a decrease in methyl-branched lipids in the KO. Overall, the results suggest a role of Rv3371 in Mtb survival in the host through its roles beyond TAG storage.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102617"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511327","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}

引用次数: 0

Functional and mechanistic insights into the stealth protein full-length CpsY is conducive to understanding immune evasion mechanisms by Mycobacterium tuberculosis 对隐身蛋白全长CpsY的功能和机制的深入了解有助于了解结核分枝杆菌的免疫逃避机制

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-02-19 DOI: 10.1016/j.tube.2025.102616

Dafeng Liu , Ablikim Abdiriyim , Lvxia Zhang , Buayxam Ruzitohti

{"title":"Functional and mechanistic insights into the stealth protein full-length CpsY is conducive to understanding immune evasion mechanisms by Mycobacterium tuberculosis","authors":"Dafeng Liu , Ablikim Abdiriyim , Lvxia Zhang , Buayxam Ruzitohti","doi":"10.1016/j.tube.2025.102616","DOIUrl":"10.1016/j.tube.2025.102616","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) is a crucial and destructive intracellular pathogen responsible for causing tuberculosis (TB), a disease of substantial morbidity and mortality. <em>Mtb</em> capsular polysaccharides can misdirect the host's immune response pathways, resulting in additional challenges in TB treatment. These capsule polysaccharides are biosynthesized by a series of stealth proteins including CpsY. Our prior investigations elucidated the structural and functional information of the central domain (aa 201–520) of CpsY within <em>Mtb</em>. However, within the host milieu, it is the full-length iteration of CpsY, rather than its truncated form CpsY<sup>201-520</sup>, that assumes pivotal roles in immune evasion. Consequently, investigating the functional mechanism of full-length CpsY is extremely important. Here, we found that the indispensable role of four conserved regions (CR1-CR4) in governing the phosphotransferase activity of full-length CpsY. Notably, the deletion of S2 (ΔS2) dramatically increased the activity compared to the wild-type (WT) full-length CpsY, thereby revealing S2 in the regulatory dynamics governing the inactivation and activation of full-length CpsY. The gene <em>cpsY</em> helps <em>Mtb</em> to survive in macrophages. Our findings were useful for the development of vaccines and immunotherapies targeting <em>Mtb</em>.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102616"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463837","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}

引用次数: 0

Unraveling the role of the immune landscape in tuberculosis granuloma 揭示免疫景观在结核肉芽肿中的作用

IF 2.8 3区医学

Tuberculosis Pub Date : 2025-02-13 DOI: 10.1016/j.tube.2025.102615

Swati Jaiswal , Samreen Fatima , Erandi Velarde de la Cruz , Satyendra Kumar

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