Pub Date : 2025-05-08DOI: 10.1016/j.tube.2025.102650
Dayna Croock , Yolandi Swart , Tomasz Janusz Sanko , Vuyo Mavumengwana , Marlo Möller , Caitlin Uren , Desiree C. Petersen
Mitochondria form an integral, yet frequently underappreciated, part of the immune response to Mycobacterium tuberculosis (M.tb), 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 M.tb 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.
{"title":"Uncharted territory: the role of mitochondrial DNA variation in macrophage-mediated host susceptibility to tuberculosis","authors":"Dayna Croock , Yolandi Swart , Tomasz Janusz Sanko , Vuyo Mavumengwana , Marlo Möller , Caitlin Uren , 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}
Pub Date : 2025-04-23DOI: 10.1016/j.tube.2025.102641
Ashley M. Divens , Kenneth J. Ryan , Alessandro Sette , Cecilia S. Lindestam Arlehamn , Cory M. Robinson
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 M. tuberculosis (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.
结核病（TB）是由病原体导致死亡的主要原因。减毒卡介苗是唯一被批准用于预防结核病的疫苗，但它不能提供长期保护。我们推测免疫抑制因子IL-27可能是卡介苗无效的原因之一。IL-27在最常接种卡介苗的新生儿中升高，接种后水平进一步升高。IL-27干扰吞噬溶酶体途径，表明它可能限制抗原加工并呈递给T细胞的多样性。我们假设，在缺乏IL-27信号的情况下，卡介苗接种诱导抗原特异性T细胞识别更多的抗原，并在结核分枝杆菌（Mtb）攻击期间提供增强的保护。新生期接种卡介苗的IL-27Rα KO小鼠分离的CD3+ T细胞对卡介苗和结核分枝杆菌肽库的反应强于接种WT小鼠的T细胞。IL-27Rα KO T细胞的过继转移比WT对Mtb具有更一致的保护作用，但在TCRα−/−小鼠中没有观察到这一点。主成分分析表明，更一致的多功能细胞因子反应与IL-27Rα KO T细胞有关。这些发现增强了我们对新生儿免疫接种和保护性免疫发展过程中IL-27的理解。
{"title":"IL-27 signaling limits the diversity of antigen-specific T cells and interferes with protection induced by BCG vaccination","authors":"Ashley M. Divens , Kenneth J. Ryan , Alessandro Sette , Cecilia S. Lindestam Arlehamn , 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<sup>+</sup> 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<sup>−/−</sup> 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}
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 Mycobacterium tuberculosis (M. tuberculosis): 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.
{"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 , Beenu Joshi , Bhawna Sharma , Santosh Kumar , Keshar Kunja Mohanty , 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}
Pub Date : 2025-04-04DOI: 10.1016/j.tube.2025.102639
Anna E. Karagianni , Lindert Benedictus , Sabine Steinbach , Femke Broere , Elisabeth M.D.L. van der Heijden
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 M. bovis 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 (ACVR2A, PIK3R1, TBX21, TGFBR1 and TGFBR2) 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.
{"title":"Characterization of the global bovine microRNAome of peripheral blood mononuclear cells isolated from Mycobacterium bovis exposed cattle","authors":"Anna E. Karagianni , Lindert Benedictus , Sabine Steinbach , Femke Broere , 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}
Pub Date : 2025-04-02DOI: 10.1016/j.tube.2025.102637
Elizna Maasdorp , Monique J. Williams
{"title":"Response to “Prevalence of non-tuberculous mycobacteria by Line-Probe Assay”","authors":"Elizna Maasdorp , Monique J. Williams","doi":"10.1016/j.tube.2025.102637","DOIUrl":"10.1016/j.tube.2025.102637","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102637"},"PeriodicalIF":2.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786188","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}
Pub Date : 2025-04-01DOI: 10.1016/j.tube.2025.102638
Pir Tariq Shah , Li Xing
Background
Ibuprofen (IBU) is a non-prescription analgesic drug from the non-steroidal anti-inflammatory drug class. It is widely used for treating pain, fever, and inflammation. Both the in silico and in vitro experiments were performed to determine the antibacterial potentials of the IBU against Mycobacterium tuberculosis (Mtb).
Methods
The STITCH v.5 pipeline was used to analyze the interaction of IBU with the proteome of the Mtb H37Ra and H37Rv strains. The GFP-tagged Bacillus Calmette Guerin (BCG) and td-tomato-tagged Mtb H37Ra were used to determine the bacteriostatic and bactericidal activities of IBU. The IBU-treated THP-1-derived macrophages were infected by td-tomato-tagged Mtb H37Ra and wild-type BCG to analyze the effects of IBU on bacterial phagocytosis and apoptosis, respectively.
Results
The in-silico study revealed that the IBU interacts with Mtb proteins primarily involved in cellular process, metabolism, and virulence, and targets four virulent proteins of Mtb, e.g., Cyp-123, Cyp-126, Cyp-130, and Cyp-139 in the cytochrome p450 system. The increasing concentrations of IBU showed significant bacteriostatic activity against Mtb H37Ra in vitro, where the 100 μg/ml and 200 μg/ml concentrations especially led to almost complete bacterial growth arrest. The IBU treatment does not affect BCG-induced apoptosis of THP-1-derived macrophages, but significantly enhances bacterial uptake, especially at 100 μg/ml and 200 μg/ml concentrations.
Conclusions
The IBU enhances Mtb uptake by macrophages and exhibits direct bacteriostatic activity in vitro.
{"title":"The anti-mycobacterial potential of ibuprofen","authors":"Pir Tariq Shah , Li Xing","doi":"10.1016/j.tube.2025.102638","DOIUrl":"10.1016/j.tube.2025.102638","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen (IBU) is a non-prescription analgesic drug from the non-steroidal anti-inflammatory drug class. It is widely used for treating pain, fever, and inflammation. Both the <em>in silico</em> and <em>in vitro</em> experiments were performed to determine the antibacterial potentials of the IBU against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>).</div></div><div><h3>Methods</h3><div>The STITCH v.5 pipeline was used to analyze the interaction of IBU with the proteome of the <em>Mtb</em> H37Ra and H37Rv strains. The GFP-tagged <em>Bacillus Calmette Guerin</em> (<em>BCG</em>) and td-tomato-tagged <em>Mtb</em> H37Ra were used to determine the bacteriostatic and bactericidal activities of IBU. The IBU-treated THP-1-derived macrophages were infected by td-tomato-tagged <em>Mtb</em> H37Ra and wild-type <em>BCG</em> to analyze the effects of IBU on bacterial phagocytosis and apoptosis, respectively.</div></div><div><h3>Results</h3><div>The <em>in-silico</em> study revealed that the IBU interacts with <em>Mtb</em> proteins primarily involved in cellular process, metabolism, and virulence, and targets four virulent proteins of <em>Mtb</em>, e.g., Cyp-123, Cyp-126, Cyp-130, and Cyp-139 in the cytochrome p450 system. The increasing concentrations of IBU showed significant bacteriostatic activity against <em>Mtb</em> H37Ra <em>in vitro</em>, where the 100 μg/ml and 200 μg/ml concentrations especially led to almost complete bacterial growth arrest. The IBU treatment does not affect <em>BCG</em>-induced apoptosis of THP-1-derived macrophages, but significantly enhances bacterial uptake, especially at 100 μg/ml and 200 μg/ml concentrations.</div></div><div><h3>Conclusions</h3><div>The IBU enhances <em>Mtb</em> uptake by macrophages and exhibits direct bacteriostatic activity <em>in vitro</em>.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102638"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783156","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}
Pub Date : 2025-03-26DOI: 10.1016/j.tube.2025.102635
Xiaochun Wang , Yun Xu , Qiangsen Zhong , Zian Zhang , LingYun Kong , Mingming Zhou , Runlin Wang , Xinxin Pi , Suwen Qiao
Mycobacterium tuberculosis (M. tb) serves as the main pathogen responsible for Tuberculosis (TB). It predominantly targets the lungs and leads to a persistent infectious disease. The spread of drug-resistant tuberculosis and the exacerbation of economic burdens due to co-infections with Human Immunodeficiency Virus (HIV)/M. tb pose significant challenges in prevention and treatment. The BCG vaccine is currently the only approved (TB) vaccine, but its protective effect is limited for adults. In this research, we engineered the fusion protein gene RPC4, incorporating four crucial antigens from M. tb. The study revealed that the IFN-γ levels in the peripheral blood of infected patients significantly surpassed those in healthy individuals. To assess the immune response of RPC4 as a BCG-enhanced vaccine following initial immunity, researchers administered it alongside the novel adjuvant DIMQ to immunize mice. Experiments revealed that the BCG + RPC4/DIMQ vaccine induces a substantial immunogenic response in the mice.
{"title":"Construction and expression of multi-stage antigen fusion protein RPC4 vaccine for Mycobacterium tuberculosis and its immunogenicity analysis in combination with adjuvant DIMQ","authors":"Xiaochun Wang , Yun Xu , Qiangsen Zhong , Zian Zhang , LingYun Kong , Mingming Zhou , Runlin Wang , Xinxin Pi , Suwen Qiao","doi":"10.1016/j.tube.2025.102635","DOIUrl":"10.1016/j.tube.2025.102635","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) serves as the main pathogen responsible for Tuberculosis (TB). It predominantly targets the lungs and leads to a persistent infectious disease. The spread of drug-resistant tuberculosis and the exacerbation of economic burdens due to co-infections with Human Immunodeficiency Virus (HIV)/<em>M. tb</em> pose significant challenges in prevention and treatment. The BCG vaccine is currently the only approved (TB) vaccine, but its protective effect is limited for adults. In this research, we engineered the fusion protein gene RPC4, incorporating four crucial antigens from <em>M. tb</em>. The study revealed that the IFN-γ levels in the peripheral blood of infected patients significantly surpassed those in healthy individuals. To assess the immune response of RPC4 as a BCG-enhanced vaccine following initial immunity, researchers administered it alongside the novel adjuvant DIMQ to immunize mice. Experiments revealed that the BCG + RPC4/DIMQ vaccine induces a substantial immunogenic response in the mice.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102635"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738964","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}
Previously, a slot blot or an indirect enzyme-linked immunosorbent assay (ELISA) using a synthetic or purified MTP antigen, conceptually demonstrated IgG antibody induction in pulmonary TB patients, albeit with small sample sizes and differing sensitivity. Therefore, we evaluated an IgG MTP ELISA in larger populations from The Gambia (n = 549), Uganda (n = 161), and South Africa (n = 193), comprising human immunodeficiency virus (HIV) positive and negative, with microbiologically confirmed active TB. The association between the IgG level and demographic characteristics was determined by multivariate logistic regression. The sensitivity (44.8–61.2 %) and specificity (33.4–78.5 %) varied in the three cohorts. Anti-MTP antibody titres differed between the TB positive and negative groups within the South African and The Gambian cohorts (p < 0.001), but not in Uganda (p = 0.35). Antibodies were detected in HIV positive and negative patients and were reduced at 6-month follow-up after treatment (p > 0.067). The study verified previous findings that anti-MTP antibodies, and therefore MTP antigen, are produced during active TB. However, the accuracy of the MTP-IgG ELISA was low, and is therefore not suitable as a target product profile in the high burden TB areas investigated. Further studies are needed to clarify the variable reactivities in different geographical areas.
{"title":"IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa","authors":"Koobashnee Pillay , Theresa Coetzer , Catherine Connolly , Balakrishna Pillay , Thamsanqa Chiliza , Kogieleum Naidoo , Jayne Sutherland , Thumbi Ndung'u , Harriet Mayanja-Kizza , Manormoney Pillay","doi":"10.1016/j.tube.2025.102634","DOIUrl":"10.1016/j.tube.2025.102634","url":null,"abstract":"<div><div>Previously, a slot blot or an indirect enzyme-linked immunosorbent assay (ELISA) using a synthetic or purified MTP antigen, conceptually demonstrated IgG antibody induction in pulmonary TB patients, albeit with small sample sizes and differing sensitivity. Therefore, we evaluated an IgG MTP ELISA in larger populations from The Gambia (n = 549), Uganda (n = 161), and South Africa (n = 193), comprising human immunodeficiency virus (HIV) positive and negative, with microbiologically confirmed active TB. The association between the IgG level and demographic characteristics was determined by multivariate logistic regression. The sensitivity (44.8–61.2 %) and specificity (33.4–78.5 %) varied in the three cohorts. Anti-MTP antibody titres differed between the TB positive and negative groups within the South African and The Gambian cohorts (p < 0.001), but not in Uganda (p = 0.35). Antibodies were detected in HIV positive and negative patients and were reduced at 6-month follow-up after treatment (p > 0.067). The study verified previous findings that anti-MTP antibodies, and therefore MTP antigen, are produced during active TB. However, the accuracy of the MTP-IgG ELISA was low, and is therefore not suitable as a target product profile in the high burden TB areas investigated. Further studies are needed to clarify the variable reactivities in different geographical areas.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102634"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714208","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}
Pub Date : 2025-03-15DOI: 10.1016/j.tube.2025.102633
Godlove T. Chaula , Lucy Namkinga , Ally Mahadhy , Wilber Sabiiti , Nyanda Elias Ntinginya , Bariki Mtafya
Background
We assessed the impact of centrifugation on recovery of Mycobacterium tuberculosis (M.tb).
Methods
We used 0.5 McFarland from the 2 weeks M. tb, H37Rv culture and homogenized sputum for our experiments. Samples were decontaminated by 2 % NaOH for 20 min and with PBS for controls. Decontaminated aliquots were centrifuged at 2000×g, 3000×g and 6000×g for 40 min and inoculated on MGIT and LJ media. MGITs were incubated into the BACTEC MGIT 960 Systems following BD manuals and data analyzed on GraphPad Software.
Results
The positivity (days) for M. tb, H37Rv in MGIT and LJ decreased from 20.4 to 17.7 and from 47.6 to 26.6 at 2000×g and 6000×g, respectively; P > 0.05. For controls, MGIT and LJ positivity (days) decreased from 19 to 10 and from 39.2 to 11.2 at 2000×g and 6000×g, respectively; P > 0.05. MGIT positivity was 6(60 %) at 2000×g and 8(80 %) at 6000×g, corresponding to mean (±SD) of 13.7 ± 6.7 and 9.06 ± 4.6 days, respectively for sputum. LJ positivity was 1(10 %) at 2000×g and 7(70 %) at 6000×g. MGIT contamination for controls (sputum) was over 50 % and 80 % for LJ.
Conclusion
Higher centrifugation speed improves yield and sensitivity of TB culture.
{"title":"High centrifugation speed improves recovery of M. tuberculosis and yield of culture","authors":"Godlove T. Chaula , Lucy Namkinga , Ally Mahadhy , Wilber Sabiiti , Nyanda Elias Ntinginya , Bariki Mtafya","doi":"10.1016/j.tube.2025.102633","DOIUrl":"10.1016/j.tube.2025.102633","url":null,"abstract":"<div><h3>Background</h3><div>We assessed the impact of centrifugation on recovery of <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>).</div></div><div><h3>Methods</h3><div>We used 0.5 McFarland from the 2 weeks <em>M. tb,</em> H37Rv culture and homogenized sputum for our experiments. Samples were decontaminated by 2 % NaOH for 20 min and with PBS for controls. Decontaminated aliquots were centrifuged at 2000×<em>g</em>, 3000×<em>g</em> and 6000×<em>g</em> for 40 min and inoculated on MGIT and LJ media. MGITs were incubated into the BACTEC MGIT 960 Systems following BD manuals and data analyzed on GraphPad Software.</div></div><div><h3>Results</h3><div>The positivity (days) for <em>M. tb</em>, <em>H37Rv</em> in MGIT and LJ decreased from 20.4 to 17.7 and from 47.6 to 26.6 at 2000×<em>g</em> and 6000×<em>g</em>, respectively; P > 0.05. For controls, MGIT and LJ positivity (days) decreased from 19 to 10 and from 39.2 to 11.2 at 2000×<em>g</em> and 6000×<em>g</em>, respectively; P > 0.05. MGIT positivity was 6(60 %) at 2000×<em>g</em> and 8(80 %) at 6000×<em>g</em>, corresponding to mean (±SD) of 13.7 ± 6.7 and 9.06 ± 4.6 days, respectively for sputum. LJ positivity was 1(10 %) at 2000×<em>g</em> and 7(70 %) at 6000×<em>g</em>. MGIT contamination for controls (sputum) was over 50 % and 80 % for LJ.</div></div><div><h3>Conclusion</h3><div>Higher centrifugation speed improves yield and sensitivity of TB culture.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102633"},"PeriodicalIF":2.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706412","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}
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