Tuberculosis最新文献

{"title":"In vitro and in vivo antibacterial activity of sudapyridine (WX-081) combined with other drugs against Mycobacterium abscessus","authors":"Hong Wang ,&nbsp;Luyao Zheng ,&nbsp;Lei Fu ,&nbsp;Weiyan Zhang ,&nbsp;Shaoyu Dong ,&nbsp;Xiaoyou Chen ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102655","DOIUrl":"10.1016/j.tube.2025.102655","url":null,"abstract":"<div><div>The management of <em>Mycobacterium abscessus</em> (MAB) infection presents formidable challenges, necessitating the development of innovative antimicrobial agents and more efficacious combination therapies. The objective of this study was to investigate the <em>in vitro</em>, <em>intracellular</em>, and <em>in vivo</em> antibacterial activity of sudapyridine (WX-081) in combination with clarithromycin (CLR), clofazimine (CFZ), rifabutin (RFB), and linezolid (LZD) against MAB. <em>In vitro</em>, the interaction between WX-081 and other drugs was assessed using the checkerboard method against MAB. Synergistic or additive effects were observed when combining WX-081 with other drugs against all strains tested. The intracellular activity of WX-081 in combination with CLR, CFZ, RFB, and LZD against the MAB reference strain in J774A.1 cells was evaluated. The combination of WX-081 and CFZ or RFB exhibited potent inhibitory activity against MAB in macrophages. To evaluate pharmacodynamics, immunosuppressed BALB/c mice were infected with MAB to establish a murine model for assessing two-drug and three-drug combinations. <em>In vivo</em> studies demonstrated that the combination of WX-081 with CLR or both CLR and CFZ displayed antibacterial activity and significantly prevented mouse mortality. Our study demonstrates that the concurrent use of WX-081 with CLR or CLR plus CFZ holds significant promise as a clinical intervention for MAB infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102655"},"PeriodicalIF":2.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230356","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":"In vitro and in vivo activities of a novel benzothiopyranone candidate NTB-3119M against Mycobacterium tuberculosis","authors":"Manyi Xu ,&nbsp;Lei Zhang ,&nbsp;Bin Wang ,&nbsp;Lei Fu ,&nbsp;Shaochen Guo ,&nbsp;Xi Chen ,&nbsp;Weiyan Zhang ,&nbsp;Gang Li ,&nbsp;Peng Li ,&nbsp;Haihong Huang ,&nbsp;Yu Lu","doi":"10.1016/j.tube.2025.102654","DOIUrl":"10.1016/j.tube.2025.102654","url":null,"abstract":"<div><h3>Objectives</h3><div>NTB-3119M, a novel benzothiopyranone derivative identified through comprehensive drug development studies, was selected as a promising antituberculosis (anti-TB) candidate. This study systematically evaluated its anti-TB efficacy <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div><em>In vitro</em> analyses encompassed antimicrobial susceptibility testing to determine minimum inhibitory concentrations (MICs) against <em>Mycobacterium tuberculosis</em> H37Rv, 10 drug-susceptible clinical isolates, and 30 multidrug-resistant (MDR) strains, alongside evaluations of minimal bactericidal concentrations (MBCs) using H37Rv and seven clinical isolates. Additionally, intracellular anti-mycobacterial activity was assessed in H37Rv-infected macrophages, and cytotoxicity was profiled through MTT assays on Vero cells. <em>In vivo</em> studies utilized acute and chronic murine tuberculosis infection models to investigate the dose-dependent efficacy of NTB-3119M (50 and 100 mg/kg) against H37Rv, with concurrent comparative histopathological analysis of lung and spleen tissues.</div></div><div><h3>Results</h3><div>NTB-3119M demonstrated superior <em>in vitro</em> potency against both drug-sensitive and drug-resistant <em>M. tuberculosis</em> strains compared to first-line agents, Isoniazid (INH), Rifampicin (RIF), Moxifloxacin (MOFX), Levofloxacin (LVFX), and Streptomycin (SM), exhibiting comparable activity to PBTZ169. Time-kill curves for NTB-3119M indicate its potent bactericidal activity. Meanwhile, No cytotoxicity was observed on Vero cells. Spontaneous resistant mutants of NTB-3119M appears at a frequency of 6.44 × 10⁻⁷ to 3.65 × 10⁻⁶. Most importantly, NTB-3119M demonstrates comparable activity of PBTZ169 and better bactericidal activity against <em>M. tuberculosis</em> than INH and RIF in the 50- and 100- mg/kg groups in acute and chronic murine models.</div></div><div><h3>Conclusion</h3><div>Our research provided comprehensive evidence that NTB-3119M with increased water solubility and bioavailability based on previous research performed excellent anti-tuberculosis activity and less cytotoxicity, which effectively tackled the undesirable drug properties associated with previous benzothiopyrone derivatives. It is warranted that NTB-3119M, as a highly promising candidate anti tuberculosis drug, deserves further research and clinical trial.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102654"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230347","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":"Gut bacterial diversity in bovines infected with Mycobacterium tuberculosis var. bovis: insights on tuberculosis pathogenesis","authors":"Cristine Cerva ,&nbsp;Fabio Marcelo de Lima ,&nbsp;Ana Paula Muterle Varela ,&nbsp;Gabriela Merker Breyer ,&nbsp;Jerônimo Miguel Vicenzi ,&nbsp;Angélica Cavalheiro Bertagnolli ,&nbsp;Vinícius Freitas Klain ,&nbsp;Franciele Maboni Siqueira ,&nbsp;Fabiana Quoos Mayer","doi":"10.1016/j.tube.2025.102652","DOIUrl":"10.1016/j.tube.2025.102652","url":null,"abstract":"<div><div>Bovine tuberculosis susceptibility and pathogenesis are influenced by host immunity, which may be modulated by the host microbiota. While intestinal microbiota composition affects pulmonary diseases in humans, its role in bovine tuberculosis remains unclear. This study explores the intestinal microbiota of cattle and its association with tuberculosis to better understand disease pathophysiology. A case-control study was conducted using small intestine content samples from cattle with and without tuberculosis, slaughtered in Rio Grande do Sul, Brazil. DNA extraction, <em>16S rRNA</em> (V4) sequencing, and bioinformatics analyses assessed alpha and beta diversity, taxa characterization, differential abundance, and metabolic pathways. No significant differences in alpha and beta diversities between the groups were detected. However, the <em>Bacillota</em>/<em>Bacteroidota</em> ratio suggested dysbiosis associated with bovine tuberculosis. Differential abundance analysis showed that microorganisms belonging to the <em>Bacillota</em> phylum, the <em>Eubacterium cellulosolvens</em> group, <em>Colidextribacter</em> and <em>Coprococcus</em> genera were enriched in healthy cattle. Conversely, animals with tuberculosis showed higher abundances of <em>Verrucomicrobiota</em> phylum, <em>Sphingomonadaceae</em> and <em>Eubacteriaceae</em> families, and <em>Solobacterium</em> and <em>Clostridia-UCG-014</em> genera. Moreover, metabolic pathways related to carbohydrate degradation were enriched in healthy animals, and biosynthetic pathways related to disease were enriched in tuberculosis animals. This study highlights associations between intestinal microbiota and bovine tuberculosis, providing insights into disease mechanisms.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102652"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177947","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":"Hippocampal syndrome secondary to tuberculosis: From neuroinflammation to neurodegeneration","authors":"José Cruz Mendoza-Torres ,&nbsp;Nayar Durán-Hernández ,&nbsp;José Alberto Choreño-Parra ,&nbsp;Carlos Sánchez-Garibay ,&nbsp;Citlaltepetl Salinas-Lara","doi":"10.1016/j.tube.2025.102653","DOIUrl":"10.1016/j.tube.2025.102653","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB), caused by <em>Mycobacterium tuberculosis</em> (Mtb), remains a primary global health concern, with significant long-term sequelae. Central nervous system TB (CNS-TB) is a clinical spectrum with entities such as tuberculous meningitis and tuberculomas. Emerging evidence suggests that Mtb may directly or indirectly affect the hippocampus, a critical memory, learning, and cognition structure.</div></div><div><h3>Objectives</h3><div>This review aims to summarize the current biological understanding of Mtb's impact on the hippocampus, elucidate its potential role in neurodegeneration, and introduce the concept of “Hippocampal syndrome secondary to tuberculosis (HSST)\" as a novel chronic entity within the CNS-TB spectrum.</div></div><div><h3>Methods</h3><div>A comprehensive literature review was conducted to analyze how Mtb gains access to the brain, its neurotropism, and the resulting neuroinflammatory and neurodegenerative effects on the hippocampus. Data from clinical, histopathological, and experimental studies were evaluated to assess potential links between TB and cognitive impairment.</div></div><div><h3>Results</h3><div>Mtb can access the CNS through hematogenous dissemination, the “Trojan Horse” mechanism, or via the olfactory pathway, bypassing the blood-brain barrier (BBB). Once in the brain, Mtb induces chronic neuroinflammation and disrupts hippocampal structure. Studies suggest that TB increases the risk of Alzheimer's and Parkinson's diseases, with evidence of Mtb-driven amyloid-beta accumulation and neuronal loss.</div><div>Furthermore, specific Mtb strains exhibit neurotropism and produce virulence factors that facilitate CNS invasion.</div></div><div><h3>Conclusions</h3><div>Understanding the interaction between TB and neurocognitive disorders is critical for improving post-TB care. Recognizing HSST as a chronic condition within the CNS-TB spectrum may support early diagnosis and targeted interventions to mitigate long-term neurological consequences.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102653"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169923","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":"Reduced host cell-free DNA as a biomarker in latent tuberculosis infection among tuberculosis contacts","authors":"Jia-Yih Feng ,&nbsp;Yen-Han Tseng ,&nbsp;Chih-Jung Chang ,&nbsp;Yu-Hsun Chiang ,&nbsp;Sheng-Wei Pan ,&nbsp;Wei-Juin Su ,&nbsp;Yuh-Min Chen","doi":"10.1016/j.tube.2025.102651","DOIUrl":"10.1016/j.tube.2025.102651","url":null,"abstract":"<div><h3>Objectives</h3><div>Circulating cell-free DNA (cfDNA), including mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (nu-cfDNA), are potential biomarkers for infectious diseases. However, cfDNA variations in TB contacts with latent tuberculosis infection (LTBI) and their potential link to a predominance of M1 monocyte polarization in LTBI remain unexplored.</div></div><div><h3>Methods</h3><div>Contacts of TB patients were screened for LTBI using the Interferon gamma (IFN-γ) release assay. Blood cfDNA was extracted, and mt-cfDNA and nu-cfDNA copy numbers were quantified by qPCR. cfDNA levels in the supernatant of M1-polarized THP-1-derived macrophages were measured.</div></div><div><h3>Results</h3><div>Levels of mt-cfDNA and nu-cfDNA were lower in the LTBI group (n = 76) than in the uninfected group (n = 58) (p = 0.012, and p &lt; 0.001). The results were consistent in an age- and sex-matched analysis (n = 41 pairs). mt-cfDNA and nu-cfDNA levels were negatively associated with the TB-specific IFN-γ response (p = 0.009, p &lt; 0.001). In the LTBI group, mt-cfDNA was negatively associated with the index case's bacterial burden (p = 0.045). In cell model, mt-cfDNA and nu-cfDNA levels in the supernatant from M1-polarized macrophage were lower than those from M2-polarized cells (p = 0.030, p = 0.045).</div></div><div><h3>Conclusions</h3><div>TB contacts with LTBI had lower cfDNA levels, which correlated with index case infectivity. Reduced cfDNA in M1-polarized macrophages warrants further investigation into the mechanisms of cfDNA reduction in LTBI.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102651"},"PeriodicalIF":2.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943226","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":"Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets","authors":"Xutao Wang ,&nbsp;Katie Harper ,&nbsp;Pranay Sinha ,&nbsp;W. Evan Johnson ,&nbsp;Prasad Patil","doi":"10.1016/j.tube.2025.102649","DOIUrl":"10.1016/j.tube.2025.102649","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB) is the leading cause of infectious disease mortality worldwide. Numerous host blood-based gene expression signatures have been proposed in the literature as alternative tools for diagnosing TB infection. However, the generalizability of these signatures to different patient contexts is not well-characterized. There is a pressing need for a well-curated database of TB gene expression studies for the systematic assessment of existing and newly developed TB gene signatures.</div></div><div><h3>Results</h3><div>We built curatedTBData, a manually-curated database of 49 human TB transcriptomic studies. This data resource is freely available through GitHub and as an R Bioconductor package that allows users to validate new and existing biomarkers without the challenges of harmonizing heterogeneous studies. We demonstrate the use of this data resource with cross-study comparisons for 72 human host blood-based TB gene signatures. For the comparison of subjects with active TB from healthy controls, 19 gene signatures had weighted mean AUC of 0.90 or greater, with the highest result of 0.94. In active TB disease versus latent TB infection, 7 gene signatures had weighted mean AUC of 0.90 or greater, with a maximum of 0.93.</div></div><div><h3>Conclusions</h3><div>The curatedTBData data package offers a comprehensive resource of curated human blood-based gene expression and clinically annotated data. This resource will facilitate the development of new signatures that are generalizable across cohorts or more applicable to specific subsets of patients.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102649"},"PeriodicalIF":2.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935982","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":"Uncharted territory: the role of mitochondrial DNA variation in macrophage-mediated host susceptibility to tuberculosis","authors":"Dayna Croock ,&nbsp;Yolandi Swart ,&nbsp;Tomasz Janusz Sanko ,&nbsp;Vuyo Mavumengwana ,&nbsp;Marlo Möller ,&nbsp;Caitlin Uren ,&nbsp;Desiree C. Petersen","doi":"10.1016/j.tube.2025.102650","DOIUrl":"10.1016/j.tube.2025.102650","url":null,"abstract":"<div><div>Mitochondria form an integral, yet frequently underappreciated, part of the immune response to <em>Mycobacterium tuberculosis (M.tb),</em> particularly within macrophages. Despite growing recognition for their role in infection and immunity, studies investigating how mitochondrial DNA (mtDNA) variation influences host susceptibility to tuberculosis (TB) are limited. Notably, there are no studies in African-based populations, although Africans possess unparalleled human genetic diversity, including the earliest diverged mitochondrial haplogroups, and a high TB burden. This underrepresentation limits the discovery of novel ancestry-specific genetic loci associated with TB. In this review article, we describe the unique characteristics of mtDNA, highlight key mitochondrial functions relevant to macrophage responses during <em>M.tb</em> infection, and summarise published studies that investigate the role of host mtDNA variation in TB susceptibility. We further advocate for the inclusion of African populations in future studies to identify novel TB susceptibility genetic risk loci and expand the current knowledgebase on host TB susceptibility.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102650"},"PeriodicalIF":2.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931917","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":"IL-27 signaling limits the diversity of antigen-specific T cells and interferes with protection induced by BCG vaccination","authors":"Ashley M. Divens ,&nbsp;Kenneth J. Ryan ,&nbsp;Alessandro Sette ,&nbsp;Cecilia S. Lindestam Arlehamn ,&nbsp;Cory M. Robinson","doi":"10.1016/j.tube.2025.102641","DOIUrl":"10.1016/j.tube.2025.102641","url":null,"abstract":"<div><div>Tuberculosis (TB) is the leading cause of death due to a pathogen. The live-attenuated BCG vaccine is the only approved vaccine to prevent TB, but it fails to confer long-term protection. We hypothesize that the immunosuppressive cytokine IL-27 may contribute to the inefficacies of the BCG vaccine. IL-27 is elevated in neonates, the population most commonly administered BCG, and levels increase further upon vaccination. IL-27 interferes with the phagolysosomal pathway, suggesting it may limit the diversity of antigens processed and presented to T cells. We hypothesized that in the absence of IL-27 signaling, BCG vaccination induces antigen-specific T cells that recognize a greater number of antigens and provide enhanced protection during <em>M. tuberculosis</em> (Mtb) challenge. CD3⁺ T cells isolated from IL-27Rα KO mice vaccinated with BCG as neonates were more responsive to BCG and a Mtb peptide pool than T cells from vaccinated WT mice. Adoptive transfer of IL-27Rα KO T cells provided more consistent protection against Mtb than WT, but this was not observed in TCRα^−/− mice. A principal component analysis suggested a more consistent multifunctional cytokine response was associated IL-27Rα KO T cells. These findings enhance our understanding of IL-27 during neonatal vaccination and development of protective immunity.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102641"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907778","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":"Customized MHC Class I & II restricted peptides from clinical isolates of Mycobacterium tuberculosis tweak strong cellular immune response in Healthy individuals and Pulmonary Tuberculosis patients: A potential candidate in vaccine design","authors":"Niharika Sharma ,&nbsp;Beenu Joshi ,&nbsp;Bhawna Sharma ,&nbsp;Santosh Kumar ,&nbsp;Keshar Kunja Mohanty ,&nbsp;Hridayesh Prakash","doi":"10.1016/j.tube.2025.102640","DOIUrl":"10.1016/j.tube.2025.102640","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a global health challenge as annual mortality rate due to drug resistant TB is increasing exponentially. This is mostly associated with the delayed diagnosis of Multidrug-resistant (MDR) or latent TB. Effective management of TB demands development of novel immunological strategies, such as peptide-based/subunit vaccines that can stimulate specific immune responses. In this context, we evaluated the immunogenic potential of two Major Histocompatibility Complex (MHC) Class I/II-restricted peptides from <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>): Rv2588c and Rv0148. The peptides were tested on T and monocyte populations from healthy donors and pulmonary TB (PTB) patients. Flow cytometry analysis revealed significant T cell activation in peripheral blood mononuclear cells (PBMC) from both groups. Enzyme-linked immunosorbent assay (ELISA) demonstrated a strong IFN-γ response, confirming effective T cell activation. Additionally, these peptides induced increased nitric oxide (NO) production in macrophages, indicating their role in activating the innate immune system. Overall, Rv2588c and Rv0148 peptides exhibited robust immunogenicity, stimulating both adaptive and innate immune responses in PBMCs from healthy and PTB individuals. These findings highlight their potential as promising TB vaccine candidates, paving the way for improved TB treatment and prevention strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102640"},"PeriodicalIF":2.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851559","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":"Characterization of the global bovine microRNAome of peripheral blood mononuclear cells isolated from Mycobacterium bovis exposed cattle","authors":"Anna E. Karagianni ,&nbsp;Lindert Benedictus ,&nbsp;Sabine Steinbach ,&nbsp;Femke Broere ,&nbsp;Elisabeth M.D.L. van der Heijden","doi":"10.1016/j.tube.2025.102639","DOIUrl":"10.1016/j.tube.2025.102639","url":null,"abstract":"<div><div>Accurate diagnostics are urgently needed for bovine TB – an economically devastating disease posing a re-emerging threat to veterinary and public health worldwide. MicroRNAs, post-transcriptional gene regulators involved in a range of biological processes and immunological pathways, have emerged as promising diagnostic biomarkers for numerous diseases. In human TB, microRNAs have been widely studied, but not much is currently known about their role in bovine TB. This study aimed to investigate the diagnostic potential of microRNAs in bTB through comprehensive analysis of their expression profiles in disparate states of <em>M. bovis</em> exposure. We used RNA-sequencing to characterize the global microRNAome of peripheral blood mononuclear cells from cattle that were either unvaccinated, BCG-vaccinated, unprotected or protected. A total of 468 microRNAs were detected across all samples, none of which were uniquely expressed in any group. Significant differential expression was observed for bta-miR-6122–3p, bta-miR-3533 and bta-miR29b in various comparisons. Subsequent target analysis of bta-miR-29b, a candidate biomarker in human tuberculosis, revealed that several genes (<em>ACVR2A</em>, <em>PIK3R1</em>, <em>TBX21</em>, <em>TGFBR1</em> and <em>TGFBR2</em>) involved in a number of relevant T-cell and immune signaling pathways, were amongst the predicted targets. Overall, this study provides evidence that microRNAs could be promising novel biomarkers for bovine TB diagnostics.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"153 ","pages":"Article 102639"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912271","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}