TuberculosisPub Date : 2024-06-08DOI: 10.1016/j.tube.2024.102531
Yannik A. Haller , Jiapei Jiang , Zijian Wan , Alexia Childress , Shaopeng Wang , Shelley E. Haydel
{"title":"M. tuberculosis PrrA binds the dosR promoter and regulates mycobacterial adaptation to hypoxia","authors":"Yannik A. Haller , Jiapei Jiang , Zijian Wan , Alexia Childress , Shaopeng Wang , Shelley E. Haydel","doi":"10.1016/j.tube.2024.102531","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102531","url":null,"abstract":"<div><p>The PrrAB two-component system (TCS) is essential for <em>Mycobacterium tuberculosis</em> viability. Previously, it was demonstrated that PrrA binds DNA in the absence of PrrB-mediated transphosphorylation and that non-cognate serine/threonine-kinases phosphorylate PrrA threonine-6 (T6). Therefore, we investigated the differential binding affinity and regulatory properties of the <em>M. tuberculosis</em>-derived wild-type PrrA, PrrA phosphomimetic (D58E, T6E), and PrrA phosphoablative (D58A, T6A) proteins with the <em>prrA</em><sup><em>Mtb</em></sup><em>, dosR</em><sup><em>Mtb</em></sup><em>,</em> and <em>cydA</em><sup><em>Mtb</em></sup> genes. While we hypothesized greater DNA binding affinity and more pronounced regulation by PrrA phosphomimetic variants, recombinant, wild-type PrrA<sup><em>Mtb</em></sup> bound DNA with greatest affinity. Collectively, wild-type PrrA<sup><em>Mtb</em></sup> recombinant protein displayed the highest binding affinity to the <em>dosR</em><sup><em>Mtb</em></sup> promoter (<em>K</em><sub><em>D</em></sub> 3.46 ± 2.09 nM), followed by the <em>prrA</em><sup><em>Mtb</em></sup> promoter (<em>K</em><sub><em>D</em></sub> 9.00 ± 2.66 nM). To establish PrrA<sup><em>Mtb</em></sup> regulatory activity, we constructed <em>M. smegmatis</em> Δ<em>prrAB</em><sup><em>Msmeg</em></sup><em>::prrA</em><sup><em>Mtb</em></sup> strains with each of the PrrA<sup><em>Mtb</em></sup> variants and extrachromosomal <em>prrA</em><sup><em>Mtb</em></sup><em>, dosR</em><sup><em>Mtb</em></sup><em>, and cyd</em><em>A</em><sup><em>Mtb</em></sup> promoter-mCherry reporter fusions. Our findings showed that PrrA<sup><em>Mtb</em></sup> is autoregulatory and induces <em>dosR</em><sup><em>Mtb</em></sup> expression only during in vitro, hypoxic growth. Combined expression of <em>prrAB</em><sup><em>Mtb</em></sup> in <em>M. smegmatis</em> Δ<em>prrAB</em> significantly induced <em>cydA</em><sup><em>Mtb</em></sup> promoter<em>-</em>mCherry expression. Our studies advanced the understanding of PrrA function and PrrAB phosphorylation-mediated regulatory mechanisms and control of mycobacterial <em>dosR</em> and <em>cydA</em> hypoxic and low-oxygen responsive genes.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102531"},"PeriodicalIF":3.2,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333334","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 : 2024-06-06DOI: 10.1016/j.tube.2024.102530
Wenlong Xu , Jihua Yang , Haizhen Yu , Shizhen Li
{"title":"Diagnostic value of lncRNAs LINC00152 and LARS2-AS1 and their regulatory roles in macrophage immune response in tuberculosis","authors":"Wenlong Xu , Jihua Yang , Haizhen Yu , Shizhen Li","doi":"10.1016/j.tube.2024.102530","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102530","url":null,"abstract":"<div><h3>Objectives</h3><p>To determine the usefulness of LINC00152 and LARS2-AS1 as potential biomarkers for latent tuberculosis (LTB) and active tuberculosis (ATB), as well as their effect on Mycobacterium (Mtb) infection.</p></div><div><h3>Methods</h3><p>The expression levels of LINC00152 and LARS2-AS1 in the health, patients with LTB and ATB were detected by qRT-PCR. The ROC curves were constructed to show their potential as biomarkers. The intracellular survival assays for Mtb and the levels of immune-related cytokines were determined to discover the effect of LINC00152 and LARS2-AS1 on Mtb infection. The relationships of miR-485-5p with LINC00152 and LARS2-AS1 were explored.</p></div><div><h3>Results</h3><p>LINC00152 and LARS2-AS1 levels were significantly elevated in patients with ATB and LTB, and Mtb-infected macrophages. LINC00152 and LARS2-AS1 can distinguish the LTB from the health and ATB from LTB. LARS2-AS1 and LINC00152 knock-down reduced the intracellular Mtb survival and induced cellular immune response after Mtb challenge. miR-485-5p was a targeting miRNA for LINC00152 and LARS2-AS1.</p></div><div><h3>Conclusions</h3><p>LINC00152 and LARS2-AS1 can be considered as potential biomarkers for tuberculosis disease. LINC00152 and LARS2-AS1 have anti-Mtb effects.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102530"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141298025","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":"Effect of Metformin on systemic chemokine responses during anti-tuberculosis chemotherapy","authors":"Nathella Pavan Kumar , Chandrasekaran Padmapriyadarsini , Arul Nancy , M. Tamizhselvan , Anant Mohan , Devarajulu Reddy , N. Poorana Ganga Devi , Prabakaran Rathinam , Bharathi Jeyadeepa , R.K. Shandil , Randeep Guleria , Manjula Singh , Subash Babu","doi":"10.1016/j.tube.2024.102523","DOIUrl":"10.1016/j.tube.2024.102523","url":null,"abstract":"<div><h3>Background</h3><p>Metformin (MET), by boosting immunity, has been suggested as a host-adjunctive therapy to anti-tuberculosis treatment (ATT).</p></div><div><h3>Methods</h3><p>We evaluated whether adding MET to the standard ATT can alter the host chemokine response. We investigated the influence of metformin on the plasma levels of a wide panel of chemokines in a group of active tuberculosis patients before treatment, at 2nd month of ATT and at 6-months of ATT as part of our clinical study to examine the effect of metformin on ATT.</p></div><div><h3>Results</h3><p>Our results demonstrated that addition of metformin resulted in diminished CC (CCL1 and CCL3) and CXC (CXCL-2 and CXCL-10) chemokines in MET arm as compared to non-MET arm at the 2nd month and 6th month of ATT. In addition to this, MET arm showed significantly diminished chemokines in individuals with high bacterial burden and cavitary disease.</p></div><div><h3>Conclusion</h3><p>Our current data suggest that metformin alters chemokines responses that could potentially curb excessive inflammation during ATT.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102523"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276796","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":"Exploring diagnostic methods for drug-resistant tuberculosis: A comprehensive overview","authors":"Andrea Sanchini , Alessio Lanni , Federico Giannoni , Alessandro Mustazzolu","doi":"10.1016/j.tube.2024.102522","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102522","url":null,"abstract":"<div><p>Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102522"},"PeriodicalIF":3.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285982","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 : 2024-05-23DOI: 10.1016/j.tube.2024.102521
Peize Zhang , Junfeng Zheng , Tingting Han , Jian Ma , Devasena Gnanashanmugam , Mengran Li , Yi-Wei Tang , Guofang Deng
{"title":"A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis","authors":"Peize Zhang , Junfeng Zheng , Tingting Han , Jian Ma , Devasena Gnanashanmugam , Mengran Li , Yi-Wei Tang , Guofang Deng","doi":"10.1016/j.tube.2024.102521","DOIUrl":"10.1016/j.tube.2024.102521","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance.</p></div><div><h3>Methods</h3><p>122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score.</p></div><div><h3>Results</h3><p>The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579–0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756–1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6–98.2%) and specificity was 81.3% (95% CI: 70.0–88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2.</p></div><div><h3>Conclusion</h3><p>Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102521"},"PeriodicalIF":3.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134795","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 : 2024-05-18DOI: 10.1016/j.tube.2024.102520
Yahav Bracha, Daniel Barkan
{"title":"A simplified and efficient method for single-step, targeted gene deletion in mycobacteria","authors":"Yahav Bracha, Daniel Barkan","doi":"10.1016/j.tube.2024.102520","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102520","url":null,"abstract":"<div><p>Targeted gene deletion in mycobacteria remain complicated, requiring expertise and multiple steps. Here we present a single-step, easy to understand and perform method for targeted gene deletion. Using this method, we successfully deleted several genes in both <em>M. smegmatis and M. abscessus</em>. We believe this method will facilitate molecular research of mycobacteria and make it accessible to a greater number of researchers throughout the world.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102520"},"PeriodicalIF":3.2,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078482","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 : 2024-05-13DOI: 10.1016/j.tube.2024.102519
Gunavanthi D. Boorgula , Tawanda Gumbo , Sanjay Singh , Pamela J. McShane , Julie V. Philley , Shashikant Srivastava
{"title":"Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation","authors":"Gunavanthi D. Boorgula , Tawanda Gumbo , Sanjay Singh , Pamela J. McShane , Julie V. Philley , Shashikant Srivastava","doi":"10.1016/j.tube.2024.102519","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102519","url":null,"abstract":"<div><h3>Background</h3><p>Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against <em>Mycobacterium abscessus</em> (Mab)<em>, Mycobacterium avium</em>-complex (MAC)<em>,</em> and <em>Mycobacterium kansasii</em> (Mkn).</p></div><div><h3>Methods</h3><p>First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains.</p></div><div><h3>Results</h3><p>Oxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for <em>M</em>. <em>avium</em>, 256 mg/L for <em>M</em>. <em>intracellulare</em>, and 4 mg/L for <em>M</em>. <em>chimaera</em> (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of <em>M. avium</em>, 4/5 <em>M. chimera</em>, but only 11/18 of <em>M. intracellulare</em> (p < 0.013).</p></div><div><h3>Conclusion</h3><p>Use of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102519"},"PeriodicalIF":3.2,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947029","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":"Bergenin potentiates BCG efficacy by enriching mycobacteria-specific adaptive memory responses via the Akt-Foxo-Stat4 axis","authors":"Suparba Mukhopadhyay , Isha Pahuja , Ahmed Abdallah Okieh , Darshana Pandey , Vinod Yadav , Ashima Bhaskar , Ved Prakash Dwivedi","doi":"10.1016/j.tube.2024.102517","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102517","url":null,"abstract":"<div><p>The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102517"},"PeriodicalIF":3.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905759","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 : 2024-05-08DOI: 10.1016/j.tube.2024.102516
María Laura Mon , Nelson Romano , Pablo Daniel Farace , Claudia A. Tortone , Delia S. Oriani , Gianluca Picariello , Martín José Zumárraga , Andrea Karina Gioffré , Paola M. Talia
{"title":"Exploring the cellulolytic activity of environmental mycobacteria","authors":"María Laura Mon , Nelson Romano , Pablo Daniel Farace , Claudia A. Tortone , Delia S. Oriani , Gianluca Picariello , Martín José Zumárraga , Andrea Karina Gioffré , Paola M. Talia","doi":"10.1016/j.tube.2024.102516","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102516","url":null,"abstract":"<div><p>Although studies on non-tuberculous mycobacteria have increased in recent years because they cause a considerable proportion of infections, their cellulolytic system is still poorly studied. This study presents a characterization of the cellulolytic activities of environmental mycobacterial isolates derived from soil and water samples from the central region of Argentina, aimed to evaluate the conservation of the mechanism for the degradation of cellulose in this group of bacteria. The molecular and genomic identification revealed identity with <em>Mycolicibacterium septicum</em>. The endoglucanase and total cellulase activities were assessed both qualitatively and quantitatively and the optimal enzymatic conditions were characterized. A specific protein of around 56 kDa with cellulolytic activity was detected in a zymogram. Protein sequences possibly arising from a cellulase were identified by mass spectrometry-based shotgun proteomics. Results showed that <em>M. septicum</em> encodes for cellulose- and hemicellulose-related degrading enzymes, including at least an active β-1,4 endoglucanase enzyme that could be useful to improve its survival in the environment. Given the important health issues related to mycobacteria, the results of the present study may contribute to the knowledge of their cellulolytic system, which could be important for their ability to survive in many different types of environments.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102516"},"PeriodicalIF":3.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910070","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":"Evaluation of AAICare®-TB sequence analysis tool for accurate diagnosis of drug-resistant tuberculosis: A comparative study with TB-Profiler and Mykrobe","authors":"Ritu Singhal , Smita Hingane , Manpreet Bhalla , Aniruddh Sharma , Sehnaz Ferdosh , Avlokita Tiwari , Praapti Jayaswal , Raj Narayan Yadav , Jyoti Arora , Ravindra Kumar Dewan , Sangeeta Sharma","doi":"10.1016/j.tube.2024.102515","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102515","url":null,"abstract":"<div><p>A rapid and comprehensive drug susceptibility test is essential for eliminating drug resistant tuberculosis. Next generation sequencing (NGS) based susceptibility testing is being explored as a potential substitute for the conventional phenotypic and genotypic testing methods. However, the adoption of NGS based genotypic susceptibility testing depends on the availability of simple, accurate and efficient analysis tools. This preliminary study aimed to evaluate the performance of a <em>Mycobacterium tuberculosis</em> (Mtb) genome analysis pipeline, AAICare®-TB, for susceptibility prediction, in comparison to two widely used gDST prediction tools, TB-Profiler and Mykrobe. This study was performed in a National Reference Laboratory in India on presumptive drug-resistant tuberculosis (DR-TB) isolates. Whole genome sequences of the 120 cultured isolates were obtained through Illumina sequencing on a MiSeq platform. Raw sequences were simultaneously analysed using the three tools. Susceptibility prediction reports thus generated, were compared to estimate the total concordance and discordance. WHO mutation catalogue (1st edition, 2021) was used as the reference standard for categorizing the mutations. In this study, AAICare®-TB was able to predict drug resistance status for First Line (Streptomycin, Isoniazid, Rifampicin, Ethambutol and Pyrazinamide) and Second Line drugs (Fluoroquinolones, Second Line Injectables and Ethionamide) in 93 samples along with lineage and hetero-resistance as per the WHO guidelines.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102515"},"PeriodicalIF":3.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918944","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}