Tuberculosis最新文献

Quinoline hybrid derivatives as effective structural motifs in the treatment of tuberculosis: Emphasis on structure-activity relationships 喹啉杂化衍生物作为治疗结核病的有效结构基团：强调结构-活性关系。

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-11-03 DOI: 10.1016/j.tube.2024.102573

{"title":"Quinoline hybrid derivatives as effective structural motifs in the treatment of tuberculosis: Emphasis on structure-activity relationships","authors":"","doi":"10.1016/j.tube.2024.102573","DOIUrl":"10.1016/j.tube.2024.102573","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis (MTB/Mtb)</em> is the causative agent of tuberculosis (TB), a highly infectious serious airborne illness. TB usually affects the lungs, in 25 % of patients (children or immune impaired adults), mycobacteria can enter the blood stream and infect other bodily areas such the meninges, pleura, lymphatic system, genitourinary system, bones, and joints. Currently, the most challenging aspect of treating this illness is the ineffectiveness of the most potent first-line anti-TB medications, isoniazid, rifampin, pyrazinamide, and ethambutol, which can result in multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB), and in rare instances, completely drug-resistant TB (TDR-TB). As a result, finding new pharmaceutical compounds to treat these diseases is a significant challenge for the scientific community. A number of bio-active molecules have been investigated in this quest, including quinoline, which is considered a promising candidate for the development of TB drugs. It is known that quinoline are low in toxicity and have a wide range of pharmacological properties. Researchers have investigated quinoline scaffolds as anti-TB drugs based on their biological spectrum. The objective of this review is to examine the recent development of quinoline and its structural characteristics crucial to its antitubercular (anti-TB) activity. A molecular analog of the TB treatment can be designed and identified with this information. As a result, future generation quinoline-based anti-TB agents with greater potency and safety can also be explored.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591358","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

Mycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination 接种疫苗一年后，牛分枝杆菌致病因子 PhoP、ESAT-6 和 CFP-10 突变体在小鼠器官中持续存在

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-11-01 DOI: 10.1016/j.tube.2024.102574

{"title":"Mycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination","authors":"","doi":"10.1016/j.tube.2024.102574","DOIUrl":"10.1016/j.tube.2024.102574","url":null,"abstract":"<div><div>A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile. Mice are the most widely used animal models in tuberculosis research, particularly for pre-clinical vaccine evaluation. In these animal models, the key indicator of infection or vaccine efficacy is the mycobacteria load in the lungs. In this study, we evaluated the long-term protection conferred by vaccinating BALB/c mice with a <em>Mycobacterium bovis</em> triple mutant lacking the virulence genes <em>phoP</em>, <em>esxA</em>, and <em>esxB</em>. Our findings showed that the triple mutant protected the lungs of mice against <em>M. bovis</em> challenge for up to one-year post-vaccination. However, the bacterial load in the spleens predominantly comprised the vaccine strain, and the lungs also contained some of these bacteria. These results suggest that the vaccine strain persisted in the mouse organs for at least one year, which raised concerns about its potential safety for animal vaccination.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592540","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

Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis 耐多药结核分枝杆菌对贝达喹啉敏感性降低的相关基因特征分析

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-10-23 DOI: 10.1016/j.tube.2024.102572

{"title":"Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102572","DOIUrl":"10.1016/j.tube.2024.102572","url":null,"abstract":"<div><div>Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log<sub>2</sub>-transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: <em>Rv0678</em>_141_ins_1 and <em>Rv1979c</em>_D249E, with effect estimates of 1.76 (95 % CI: 0.67–2.84) and 1.69 (95 % CI: 0.22–3.17), respectively. Other implicated genes included <em>Rv2699c</em>_-84_del_1, <em>hsaB</em>_I179T, <em>mmpL9</em>_T241A, <em>pncA</em>_C14R, <em>Rv0373c</em>_G621S, <em>Rv0893c</em>_L27F, <em>Rv1770</em>_A4D, and <em>Rv3428c</em>_S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587296","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

Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis 吲哚分枝杆菌和人类 beta Defensin-2 作为结核分枝杆菌辅助疗法的协同作用。

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-10-15 DOI: 10.1016/j.tube.2024.102571

{"title":"Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102571","DOIUrl":"10.1016/j.tube.2024.102571","url":null,"abstract":"<div><div>Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, <em>Mycobacterium indicus pranii (MIP)</em> and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by <em>Mycobacterium smegmatis</em> (<em>M.</em><em>smeg</em>) and <em>Mycobacterium tuberculosis (M</em>.<em>tb)</em> (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against <em>M.tb</em> by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508880","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

Combining bioinformatics and machine learning to identify diagnostic biomarkers of TB associated with immune cell infiltration 结合生物信息学和机器学习，确定与免疫细胞浸润相关的结核病诊断生物标志物

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-10-11 DOI: 10.1016/j.tube.2024.102570

{"title":"Combining bioinformatics and machine learning to identify diagnostic biomarkers of TB associated with immune cell infiltration","authors":"","doi":"10.1016/j.tube.2024.102570","DOIUrl":"10.1016/j.tube.2024.102570","url":null,"abstract":"<div><h3>Objective</h3><div>The asymptomatic nature of tuberculosis (TB) during its latent phase, combined with limitations in current diagnostic methods, makes accurate diagnosis challenging. This study aims to identify TB diagnostic biomarkers by integrating gene expression screening with machine learning, evaluating their diagnostic potential and correlation with immune cell infiltration.</div></div><div><h3>Methods</h3><div>We analyzed GSE19435, GSE19444, and GSE54992 datasets to identify differentially expressed genes (DEGs). GO and KEGG enrichment characterized gene functions. Three machine learning algorithms identified potential biomarkers, validated with GSE83456, GSE62525, and RT-qPCR on clinical samples. Immune cell infiltration was analyzed and verified with blood data.</div></div><div><h3>Results</h3><div>249 DEGs were identified, with PDE7A and DOK3 emerging as potential biomarkers. RT-qPCR confirmed their expression, showing AUCs above 0.75 and a combined AUC of 0.926 for TB diagnosis. Immune infiltration analysis revealed strong correlations between PDE7A, DOK3, and immune cells.</div></div><div><h3>Conclusion</h3><div>PDE7A and DOK3 show strong diagnostic potential for TB, closely linked to immune cell infiltration, and may serve as promising biomarkers and therapeutic targets.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442504","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 C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis 一种新型 C-4 改性异四氢呋喃可作为一种有效的生物增强剂，增强抗结核药物对结核分枝杆菌的活性。

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-09-27 DOI: 10.1016/j.tube.2024.102569

{"title":"A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102569","DOIUrl":"10.1016/j.tube.2024.102569","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of <em>C</em>-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of <em>M. tuberculosis</em> H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of <em>M. tuberculosis</em> and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366685","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

Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection 结核病与 T 细胞结核感染中 T 细胞多样性的影响

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-09-18 DOI: 10.1016/j.tube.2024.102567

{"title":"Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection","authors":"","doi":"10.1016/j.tube.2024.102567","DOIUrl":"10.1016/j.tube.2024.102567","url":null,"abstract":"<div><p>Tuberculosis is a global threat and is still a leading cause of death due to an infectious agent. The infection is spread through inhalation of <em>M. tb</em> containing aerosol droplets. Bacteria after reaching the lung alveoli are engulfed by alveolar macrophages, leading to an immune response. Then, pro-inflammatory cytokines are released by these macrophages, recruiting other antigen-presenting cells like dendritic cells. These cells phagocytose the bacteria and present mycobacterial antigens to naïve T cells. After activation by DCs, T cells differentiate into various T cells subsets, viz. CD4<sup>+</sup>, CD8<sup>+</sup>, Th17, Treg, Tfh cells and others display enormous diversification in their characteristics and functions. This review comprises a comprehensive literature on conventional and unconventional T cells, highlighting the polyfunctional T cells as well, their role in controlling TB infection, and their implications in the spectrum of TB infection. While some subsets such as CD4<sup>+</sup> T cells are extensively studied, some T cell subsets such as gamma delta T cells and Tfh cells remain poorly understood in the pathophysiology of tuberculosis, despite having significant potential implications. The goal of TB eradication can be assisted by development of better vaccines against TB, which can effectively induce a robust and long-term T cells memory. The same has been discussed in the latter part of this review. BCG being the standalone commercialised TB vaccine so far has its limitations. Strategies for the enhancement of BCG along with novel studies in vaccine development, has also been discussed in great detail. Lastly, T cells display a complex interplay of an adaptive immune response against TB, with activation and enhancement of the innate immune responses. Therefore, it is critical to fully understand the role of various T cells subsets in pathophysiology of tuberculosis to provide better therapeutic inventions and improve patient care.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274808","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 description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia 印度尼西亚巴布亚地区结核分枝杆菌 1 系的描述

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-09-14 DOI: 10.1016/j.tube.2024.102568

{"title":"A description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia","authors":"","doi":"10.1016/j.tube.2024.102568","DOIUrl":"10.1016/j.tube.2024.102568","url":null,"abstract":"<div><div>Indonesia has the third highest number of tuberculosis (TB) patients infected with Mycobacterium tuberculosis (<em>MTB</em>) Lineage 1 (L1). Most of these MTB L1 cases can be found in Indonesia's remote easternmost province of Papua, one of Indonesia's most underdeveloped provinces with a particularly high burden for TB. In this study, we sequenced and described 42 <em>MTB</em> L1 isolates from a well-characterized cohort of patients. We found a genetically diverse <em>MTB</em> L1 population with no association between pathogen genetic relatedness and place of residence or pathogen genetic relatedness and patient ethnicity, which could reflect mixing between different locales and ethnicities or our low sampling fraction. Only a small number showed genetic variants associated with drug resistance (5/42, 11.9 %), probably due to a lack of effective treatment programs. The Papuan isolates showed similarities to other Island Southeast Asian Countries due to the high proportion of L1.2.1.2.1 (30/42, 71.4 %), especially East Timor and the Philippines. This study fills a research gap of MTB L1 in Indonesian Papua and should serve as a stepping stone for further research in the region.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000945/pdfft?md5=a6f4d495c84889622c44816e926c96f8&pid=1-s2.0-S1472979224000945-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315327","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

Exhaled breath analysis: A promising triage test for tuberculosis in young children 呼气分析：有望成为幼儿结核病分诊测试的方法

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-09-10 DOI: 10.1016/j.tube.2024.102566

引用次数: 0

Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo) 评估转录标记以区分自由活动的带状金钱豹（Mungos mungo）的孟氏分枝杆菌感染状况

IF 2.8 3区医学

Tuberculosis Pub Date : 2024-09-05 DOI: 10.1016/j.tube.2024.102565

{"title":"Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo)","authors":"","doi":"10.1016/j.tube.2024.102565","DOIUrl":"10.1016/j.tube.2024.102565","url":null,"abstract":"<div><p>There is an increasingly urgent need to improve our ability to accurately forecast and control zoonotic diseases in wildlife reservoirs. We are confronted, however, with the continued challenge of accurately determining host infection status across space and time. This dilemma is epitomized with the <em>Mycobacterium tuberculosis</em> Complex (MTBC) pathogens and particularly in free-ranging wildlife, a critical global challenge for both human and animal health. In humans, transcriptional markers have been increasingly identified as a robust tool for diagnosing <em>Mycobacterium tuberculosis</em> (<em>MTB</em>) infection status but have rarely been utilized for diagnosing TB in free-ranging wildlife populations. Here, we report the first use of transcriptional markers to evaluate TB infection status in a free-ranging wildlife species, banded mongoose (<em>Mungos mungo</em>), infected with the MTBC pathogen, <em>Mycobacterium mungi</em>. In this study, we found that <em>GBP5</em> and <em>DUSP3</em> were significantly upregulated in free-ranging banded mongoose infected with <em>M. mungi</em>. These results provide the first step in developing an antemortem diagnostic tool for use in free-ranging wildlife species. Our results highlight the potential of transcriptional marker-based assays to advance our ability to detect and manage TB in free-ranging wildlife, especially in field studies and other scenarios when conventional diagnostics are not feasible.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241236","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