{"title":"Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection","authors":"Deepak Vats, Geeta Rani, Alisha Arora, Vidushi Sharma, Isha Rathore, Shaikh Abdul Mubeen, Archana Singh","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":"149 ","pages":"Article 102567"},"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}
TuberculosisPub Date : 2024-09-14DOI: 10.1016/j.tube.2024.102568
Hanif A.K. Djunaedy , Clarissa A. Febinia , Raph L. Hamers , Kevin Baird , Iqbal Elyazar , Nguyen Thuy Thuong Thuong , Hidayat Trimarsanto , Safarina G. Malik , Guy Thwaites , Reinout van Crevel , Bachti Alisjahbana , Lidya Chaidir , Philip M. Ashton
{"title":"A description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia","authors":"Hanif A.K. Djunaedy , Clarissa A. Febinia , Raph L. Hamers , Kevin Baird , Iqbal Elyazar , Nguyen Thuy Thuong Thuong , Hidayat Trimarsanto , Safarina G. Malik , Guy Thwaites , Reinout van Crevel , Bachti Alisjahbana , Lidya Chaidir , Philip M. Ashton","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":"149 ","pages":"Article 102568"},"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}
TuberculosisPub Date : 2024-09-10DOI: 10.1016/j.tube.2024.102566
Else M. Bijker , Jonathan P. Smith , Walter Mchembere , Kimberly D. McCarthy , Henny Oord , Jan-Willem Gerritsen , Eleanor S. Click , Kevin Cain , Rinn Song
{"title":"Exhaled breath analysis: A promising triage test for tuberculosis in young children","authors":"Else M. Bijker , Jonathan P. Smith , Walter Mchembere , Kimberly D. McCarthy , Henny Oord , Jan-Willem Gerritsen , Eleanor S. Click , Kevin Cain , Rinn Song","doi":"10.1016/j.tube.2024.102566","DOIUrl":"10.1016/j.tube.2024.102566","url":null,"abstract":"<div><div>The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.</div><div>We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.</div><div>Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62–96 %), this resulted in a specificity of 42 % (95 % CI 30–55 %).</div><div>Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102566"},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322603","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}
TuberculosisPub Date : 2024-09-05DOI: 10.1016/j.tube.2024.102565
Nicholas M. Sybertz , Shamim Al Jubaer , Michelle H. Larsen , Kathleen A. Alexander
{"title":"Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo)","authors":"Nicholas M. Sybertz , Shamim Al Jubaer , Michelle H. Larsen , Kathleen A. Alexander","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":"149 ","pages":"Article 102565"},"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}
TuberculosisPub Date : 2024-08-30DOI: 10.1016/j.tube.2024.102555
Igor Mokrousov , Maria Badleeva , Regina Mudarisova , Valery Kozhevnikov , Andrey Markhaev , Anastasia Guntupova , Anna Vyazovaya
{"title":"Increasing circulation of multi-drug resistant tuberculosis strains in Buryatia, high-burden and ethnically diverse region in the Russian Far East","authors":"Igor Mokrousov , Maria Badleeva , Regina Mudarisova , Valery Kozhevnikov , Andrey Markhaev , Anastasia Guntupova , Anna Vyazovaya","doi":"10.1016/j.tube.2024.102555","DOIUrl":"10.1016/j.tube.2024.102555","url":null,"abstract":"<div><p>Buryatia is a multidrug-resistant tuberculosis (MDR-TB) high-burden region in the Russian Far East with ethnically diverse population (30 % Mongoloid Buryats and 65 % Russians). Two hundred <em>M. tuberculosis</em> strains from newly-diagnosed patients were subjected to phenotypic testing and genotyping. The Beijing genotype was more prevalent among Russians than Buryats (68 % vs 53 %; P = 0.055). European non-Beijing genotypes (LAM, Ural, Haarlem) were double more prevalent in Buryats vs Russians (39.2 % vs 20.5 %; P = 0.01). Higher prevalence of Beijing among former prison inmates (79 % vs 61 % in other patients, P = 0.1) suggests its increased transmissibility. The Russian epidemic cluster B0/W148 was in 9.5 %, double smaller than elsewhere in Siberia. The hypervirulent Beijing 14717-15-cluster was endemic in Buryatia but paradoxically enough, it was more frequently isolated from Russians than Buryats (9.1 % vs 3.9 %; P = 0.2). Beijing subtypes B0/W148, CAO, and 14717-15 were associated with poly/multi-drug resistance (P = 0.01–0.0001). HIV coinfection was more frequent in Russians than in Buryats: 35/141 (24.8 %) vs 5/51 (9.8 %), P = 0.03. To conclude, <em>M. tuberculosis</em> population structure in Buryatia retained its singularities compared to other parts of Russia and remains strikingly different from the neighboring Mongolia. A circulation of strongly MDR-associated Beijing subtypes and drug-resistant non-Beijing strains highlights a risk of their broader dissemination.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102555"},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146406","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}
TuberculosisPub Date : 2024-08-28DOI: 10.1016/j.tube.2024.102556
Margarita O. Shleeva , Boris V. Nikonenko , Konstantin B. Majorov , Pavel Yu Ivanov , Alexander S. Apt , Valeria S. Velezheva
{"title":"Indole triazene compound TU112 demonstrates in vitro activity against dormant Mycobacterium tuberculosis and efficacy against chronic tuberculosis infection in mice","authors":"Margarita O. Shleeva , Boris V. Nikonenko , Konstantin B. Majorov , Pavel Yu Ivanov , Alexander S. Apt , Valeria S. Velezheva","doi":"10.1016/j.tube.2024.102556","DOIUrl":"10.1016/j.tube.2024.102556","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102556"},"PeriodicalIF":2.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121903","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}
TuberculosisPub Date : 2024-07-31DOI: 10.1016/j.tube.2024.102554
Sosina Ayalew , Teklu Wegayehu , Binium Wondale , Dawit Kebede , Mahlet Osman , Sebsib Niway , Azeb Tarekegn , Bamlak Tessema , Stefan Berg , Roland T. Ashford , Adane Mihret
{"title":"Detection of Mycobacterium tuberculosis complex in saliva by quantitative PCR: A potential alternative specimen for pulmonary tuberculosis diagnosis","authors":"Sosina Ayalew , Teklu Wegayehu , Binium Wondale , Dawit Kebede , Mahlet Osman , Sebsib Niway , Azeb Tarekegn , Bamlak Tessema , Stefan Berg , Roland T. Ashford , Adane Mihret","doi":"10.1016/j.tube.2024.102554","DOIUrl":"10.1016/j.tube.2024.102554","url":null,"abstract":"<div><h3>Background</h3><p>Current tuberculosis (TB) diagnostic tests primarily rely on sputum samples, yet many TB patients cannot produce sputum. This study explored whether saliva could be used instead of sputum to diagnose pulmonary TB (PTB).</p></div><div><h3>Method</h3><p>The study included 32 patients with confirmed PTB and 30 patients with other respiratory diseases (ORD). Saliva from all study participants was subjected to quantitative (qPCR) assays targeting the IS<em>1081</em> gene for detection of <em>M. tuberculosis complex</em> DNA.</p></div><div><h3>Results</h3><p>The sensitivity of saliva IS<em>1081</em> qPCR was 65.6 % (95 % CI 48.4–80.2 %) with positive results for 21/32 PTB cases, while the specificity was 96.7 % (95 % CI 85.9–99.6 %) with negative results for 29/30 participants with ORD. Sensitivity improved to 72.4 % (95 % CI 54.6–86.0 %) when sputum-Xpert was used as the reference standard, while remaining similar at 65.5 % (95 % CI 47.4–80.7 %) when culture was used as the reference standard. In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for saliva IS<em>1081</em> qPCR was 82.5 % (95 % CI 71.7–93.3 %).</p></div><div><h3>Conclusion</h3><p>Saliva testing offers a promising alternative to sputum for TB diagnosis among confirmed PTB cases. Larger multicenter studies, encompassing diverse clinical TB characteristics, are needed to provide improved estimates of diagnostic sensitivity and specificity.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102554"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879471","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}
TuberculosisPub Date : 2024-07-31DOI: 10.1016/j.tube.2024.102553
Mohd Rahimi Muda , Orwa Albitar , Sabariah Noor Harun , Syed Azhar Syed Sulaiman , Irfhan Ali Hyder Ali , Siti Maisharah Sheikh Ghadzi
{"title":"A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation","authors":"Mohd Rahimi Muda , Orwa Albitar , Sabariah Noor Harun , Syed Azhar Syed Sulaiman , Irfhan Ali Hyder Ali , Siti Maisharah Sheikh Ghadzi","doi":"10.1016/j.tube.2024.102553","DOIUrl":"10.1016/j.tube.2024.102553","url":null,"abstract":"<div><p>Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44–0.84) and 0.67, 95 % CI (0.53–0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23–0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35–0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102553"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879470","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}
TuberculosisPub Date : 2024-07-31DOI: 10.1016/j.tube.2024.102552
Balázs Tihanyi , Levente Samu , István Koncz , Kristóf Hergott , Pál Medgyesi , György Pálfi , Krisztina Ágnes Szabó , Luca Kis , Antónia Marcsik , Erika Molnár , Olga Spekker
{"title":"A glimpse into the past of Hansen's disease – Re-evaluation and comparative analysis of cases with leprosy from the Avar period of the Trans-Tisza region, Hungary","authors":"Balázs Tihanyi , Levente Samu , István Koncz , Kristóf Hergott , Pál Medgyesi , György Pálfi , Krisztina Ágnes Szabó , Luca Kis , Antónia Marcsik , Erika Molnár , Olga Spekker","doi":"10.1016/j.tube.2024.102552","DOIUrl":"10.1016/j.tube.2024.102552","url":null,"abstract":"<div><p>Our knowledge of how society viewed leprosy and treated its victims in the past is still scarce, especially in geographical regions and archaeological periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of five previously described, probable cases with leprosy from the Avar-period Trans-Tisza region (Hungary). The five skeletons were subject to a detailed macromorphological (re-)evaluation. Where possible, the biological and social consequences of having leprosy were reconstructed based on the observed bony changes and mortuary treatment, respectively. The retrospective, macromorphology-based diagnosis of leprosy could be established in three cases only. Based on the detected skeletal lesions, all of them suffered from near-lepromatous or lepromatous leprosy. The disease resulted in aesthetic repercussions and functional implications, which would have been disadvantageous for these individuals, and limited or changed their possibilities to participate in social situations. They could have even required heavy time investment from their respective communities. The analysis of the mortuary treatment of the confirmed leprosy cases revealed no evidence of a social stigma. These findings indicate that the afflicted have not been systematically expulsed or segregated, at least in death, in the Early Middle Ages of the Carpathian Basin.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102552"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000787/pdfft?md5=68a1f057b3b4b6cf8b126d76664314ee&pid=1-s2.0-S1472979224000787-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978326","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}
TuberculosisPub Date : 2024-07-26DOI: 10.1016/j.tube.2024.102551
Jin-Tian Xu , Yi Lin , Tao Cheng , Jiao-Yu Deng
{"title":"The rv2820c K114N mutation is related with capreomycin tolerance","authors":"Jin-Tian Xu , Yi Lin , Tao Cheng , Jiao-Yu Deng","doi":"10.1016/j.tube.2024.102551","DOIUrl":"10.1016/j.tube.2024.102551","url":null,"abstract":"<div><p>As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 <em>Mycobacterium tuberculosis</em> clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the <em>rv2820c</em> gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%). However, the mutation was also observed in capreomycin-sensitive isolates (10/394, 2.53%). In most cases (31/42, 73.81%), the <em>rv2820c</em> K114N mutation occurred in isolates with the known capreomycin resistance conferring mutation <em>rrs</em> A1401G. In contrast, the general frequency of the <em>rv2820c</em> K114N mutation was low in 7061 genomes downloaded from the National Center for Biotechnology Information database. To determine the impact of this mutation on the antimycobacterial activity of capreomycin, the intact <em>rv2820c</em> gene and the <em>rv2820c</em> K114N mutant were over-expressed in <em>Mycobacterium smegmatis</em> (<em>Ms</em>), and the results of susceptibility tests showed that the <em>rv2820c</em> K114N mutation did not affect the minimum inhibition concentration (MIC) of capreomycin. Subsequently, the data of time-kill assays showed that, it took only 2 h of capreomycin treatment (40 μg/ml, 5 × MIC) to kill 99.9% bacterial cells of <em>Ms</em> MC<sup>2</sup>155 pMV261::<em>rv2820c</em><sub>H37Rv</sub>, while it took 6 h to achieve that for <em>Ms</em> MC<sup>2</sup>155 pMV261::<em>rv2820c</em><sub>K114N</sub>. Taken together, these data suggested that the <em>rv2820c</em> K114N mutation is related with capreomycin tolerance, which merits further investigation.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102551"},"PeriodicalIF":2.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845544","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}