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Response to “Prevalence of non-tuberculous mycobacteria by Line-Probe Assay” 对“线探针法检测非结核分枝杆菌患病率”的回应
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-04-02 DOI: 10.1016/j.tube.2025.102637
Elizna Maasdorp , Monique J. Williams
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引用次数: 0
The anti-mycobacterial potential of ibuprofen 布洛芬的抗分枝杆菌潜能
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-04-01 DOI: 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.
背景布洛芬(IBU)是一种非处方镇痛药,属于非甾体抗炎药类。它被广泛用于治疗疼痛、发烧和炎症。为了确定 IBU 对结核分枝杆菌(Mtb)的抗菌潜力,我们进行了硅学和体外实验。方法使用 STITCH v.5 管道分析 IBU 与 Mtb H37Ra 和 H37Rv 菌株蛋白质组的相互作用。用GFP标记的卡介苗(Bacillus Calmette Guerin,BCG)和td-tomato标记的Mtb H37Ra来测定IBU的抑菌和杀菌活性。IBU处理的THP-1衍生巨噬细胞分别被td-番茄标记的Mtb H37Ra和野生型卡介苗感染,以分析IBU对细菌吞噬和细胞凋亡的影响、细胞色素 p450 系统中的 Cyp-123、Cyp-126、Cyp-130 和 Cyp-139 。在体外,浓度不断增加的 IBU 对 Mtb H37Ra 有明显的抑菌作用,尤其是 100 μg/ml 和 200 μg/ml 浓度的 IBU 几乎完全抑制了细菌的生长。IBU 处理不会影响卡介苗诱导的 THP-1 巨噬细胞的凋亡,但会显著增强细菌的吸收,尤其是在 100 μg/ml 和 200 μg/ml 的浓度下。
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引用次数: 0
Construction and expression of multi-stage antigen fusion protein RPC4 vaccine for Mycobacterium tuberculosis and its immunogenicity analysis in combination with adjuvant DIMQ 多阶段抗原融合蛋白RPC4结核分枝杆菌疫苗的构建、表达及与佐剂DIMQ联合免疫原性分析
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-26 DOI: 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.
结核分枝杆菌(M. tb)是导致结核病的主要病原体。它主要以肺部为目标,并导致一种持续的传染病。耐药结核病的蔓延和人类免疫缺陷病毒(HIV)/M合并感染造成的经济负担加剧。结核病在预防和治疗方面构成重大挑战。卡介苗是目前唯一被批准的(结核病)疫苗,但它对成人的保护作用有限。在这项研究中,我们设计了融合蛋白基因RPC4,结合了结核分枝杆菌的四种关键抗原。研究表明,感染患者外周血中的IFN-γ水平明显超过健康个体。为了评估RPC4作为bcg增强疫苗在初始免疫后的免疫反应,研究人员将其与新型佐剂DIMQ一起给予小鼠免疫。实验表明,卡介苗+ RPC4/DIMQ疫苗在小鼠体内诱导了大量的免疫原性应答。
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引用次数: 0
Prevalence of non-tuberculous mycobacteria estimated by line-probe assay 用线探针法估计非结核分枝杆菌的患病率
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-26 DOI: 10.1016/j.tube.2025.102636
Sarman Singh
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引用次数: 0
IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa 撒哈拉以南非洲不同地理区域人群对毛卷曲结核分枝杆菌(MTP)的IgG抗体反应
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.tube.2025.102634
Koobashnee Pillay , Theresa Coetzer , Catherine Connolly , Balakrishna Pillay , Thamsanqa Chiliza , Kogieleum Naidoo , Jayne Sutherland , Thumbi Ndung'u , Harriet Mayanja-Kizza , Manormoney Pillay
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.
以前,使用合成或纯化的MTP抗原的槽印迹或间接酶联免疫吸附试验(ELISA)在概念上证明了IgG抗体对肺结核患者的诱导作用,尽管样本量小且敏感性不同。因此,我们在冈比亚(n = 549)、乌干达(n = 161)和南非(n = 193)的更大人群中评估了IgG MTP ELISA,包括人类免疫缺陷病毒(HIV)阳性和阴性,微生物学证实为活动性结核病。IgG水平与人口统计学特征之间的关系通过多变量logistic回归确定。三个队列的敏感性(44.8 - 61.2%)和特异性(33.4 - 78.5%)各不相同。抗mtp抗体滴度在南非和冈比亚队列中结核阳性和阴性组之间存在差异(p <;0.001),但乌干达没有(p = 0.35)。在HIV阳性和阴性患者中检测到抗体,并在治疗后6个月随访时降低(p >;0.067)。该研究证实了以前的发现,即在活动性结核病期间产生抗MTP抗体,从而产生MTP抗原。然而,MTP-IgG ELISA的准确性较低,因此不适合作为所调查的高负担结核病地区的目标产品。需要进一步的研究来阐明不同地理区域的不同反应性。
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引用次数: 0
High centrifugation speed improves recovery of M. tuberculosis and yield of culture 高离心速度可提高结核分枝杆菌的回收率和培养产量
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-15 DOI: 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.
我们评估了离心对结核分枝杆菌(M.tb)回收的影响。方法采用2周结核分枝杆菌、H37Rv培养液和匀浆痰液0.5 McFarland进行实验。样品用2% NaOH净化20分钟,用PBS作为对照。净化后的等分液在2000×g、3000×g和6000×g离心40分钟,接种于MGIT和LJ培养基。根据BD手册和GraphPad软件分析的数据,将MGIT培养到BACTEC MGIT 960系统中。结果MGIT和LJ中结核分枝杆菌、H37Rv在2000×g和6000×g的阳性(d)分别由20.4和47.6降至17.7和26.6;P比;0.05. 对照中,在2000×g和6000×g, MGIT和LJ阳性(天)分别从19降至10天和从39.2降至11.2天;P比;0.05. 在2000×g和6000×g, MGIT阳性分别为6(60%)和8(80%),对应于痰液的平均(±SD)分别为13.7±6.7和9.06±4.6天。LJ阳性在2000×g为1例(10%),在6000×g为7例(70%)。对照组(痰)MGIT污染超过50%,LJ超过80%。结论较高的离心速度可提高结核杆菌培养的产率和灵敏度。
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引用次数: 0
Functional analysis of genetic mutations in ddn and fbiA linked to delamanid resistance in rifampicin-resistant Mycobacterium tuberculosis 耐利福平结核分枝杆菌中与德拉曼耐药相关的ddn和fbiA基因突变的功能分析
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.tube.2025.102630
Seungmo Kim , Seung Heon Lee , Gisu Kang , Gyeong In Lee , Hyeon-Su Kim , Jeong Seong Yang , Youngsuk Park , Byoung Oh Hwang , Hyejin Kim
The connection between genetic mutations linked to delamanid resistance and phenotypic resistance remains unclear. We assessed the phenotypic effects of delamanid-resistant mutations in the Mycobacterium tuberculosis H37Rv strain through gene disruption using homologous recombination and complementation tests. Delamanid resistance was assessed by determining the minimum inhibitory concentration (MIC) via the 7H9 microdilution method. Sanger sequencing identified mutations, and conservation of the mutated residues was predicted through multiple sequence alignments of orthologs. A total of 116 isolates with MIC ≥0.025 μg/mL were analyzed, among which mutations were identified in the ddn and fbiA genes. Isogenic strains were generated based on these mutations. The ddn or fbiA isogenic strains with Ala77Val, Gly81Ser, Asn25fs, and Leu104Phe in fbiA had MICs ≥0.8 μg/mL, indicating resistance. In contrast, the ddn isogenic strain with Pro12Ala had an MIC of 0.012 μg/mL, showing susceptibility, while Gly96Asp in fbiA had an MIC of 0.1 μg/mL, indicating resistance. All mutations, except for Pro12Ala, were conserved in the protein sequences of both FbiA and Ddn and their mycobacterial orthologs. The characterization of these mutations provides insights into the mechanisms of delamanid resistance, which may inform the development of optimized treatment strategies.
与delamanid抗性相关的基因突变与表型抗性之间的联系尚不清楚。我们利用同源重组和互补试验对结核分枝杆菌H37Rv菌株进行基因破坏,评估了delamanid耐药突变的表型效应。通过7H9微量稀释法测定最小抑菌浓度(MIC)来评估Delamanid耐药性。Sanger测序鉴定突变,并通过多个同源物序列比对预测突变残基的保守性。共检测到MIC≥0.025 μg/mL的分离株116株,其中ddn和fbiA基因突变。基于这些突变产生了等基因菌株。fbiA中含有Ala77Val、Gly81Ser、Asn25fs和Leu104Phe的ddn或fbiA等基因菌株mic≥0.8 μg/mL,提示耐药。与此相反,含有Pro12Ala的ddn等基因菌株的MIC为0.012 μg/mL,表现为敏感性,而含有fbiA的Gly96Asp的MIC为0.1 μg/mL,表现为抗性。除Pro12Ala外,所有突变在FbiA和Ddn及其分枝杆菌同源物的蛋白序列中都是保守的。这些突变的特征提供了对delamanid耐药机制的深入了解,这可能为优化治疗策略的发展提供信息。
{"title":"Functional analysis of genetic mutations in ddn and fbiA linked to delamanid resistance in rifampicin-resistant Mycobacterium tuberculosis","authors":"Seungmo Kim ,&nbsp;Seung Heon Lee ,&nbsp;Gisu Kang ,&nbsp;Gyeong In Lee ,&nbsp;Hyeon-Su Kim ,&nbsp;Jeong Seong Yang ,&nbsp;Youngsuk Park ,&nbsp;Byoung Oh Hwang ,&nbsp;Hyejin Kim","doi":"10.1016/j.tube.2025.102630","DOIUrl":"10.1016/j.tube.2025.102630","url":null,"abstract":"<div><div>The connection between genetic mutations linked to delamanid resistance and phenotypic resistance remains unclear. We assessed the phenotypic effects of delamanid-resistant mutations in the <em>Mycobacterium tuberculosis</em> H37Rv strain through gene disruption using homologous recombination and complementation tests. Delamanid resistance was assessed by determining the minimum inhibitory concentration (MIC) via the 7H9 microdilution method. Sanger sequencing identified mutations, and conservation of the mutated residues was predicted through multiple sequence alignments of orthologs. A total of 116 isolates with MIC ≥0.025 μg/mL were analyzed, among which mutations were identified in the <em>ddn</em> and <em>fbiA</em> genes. Isogenic strains were generated based on these mutations. The <em>ddn</em> or <em>fbiA</em> isogenic strains with Ala77Val, Gly81Ser, Asn25fs, and Leu104Phe in <em>fbiA</em> had MICs ≥0.8 μg/mL, indicating resistance. In contrast, the <em>ddn</em> isogenic strain with Pro12Ala had an MIC of 0.012 μg/mL, showing susceptibility, while Gly96Asp in <em>fbiA</em> had an MIC of 0.1 μg/mL, indicating resistance. All mutations, except for Pro12Ala, were conserved in the protein sequences of both FbiA and Ddn and their mycobacterial orthologs. The characterization of these mutations provides insights into the mechanisms of delamanid resistance, which may inform the development of optimized treatment strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"152 ","pages":"Article 102630"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chasing the “White Plague” in the Barbaricum of the Carpathian Basin – A case with tuberculous meningitis discovered in a Sarmatian-period (2nd–3rd-century-CE) storage pit from the archaeological site of Kiskundorozsma–Daruhalom-dűlő II (Hungary) 在喀尔巴阡盆地的野蛮地区追逐“白色瘟疫”——在匈牙利Kiskundorozsma-Daruhalom-dűlő II考古遗址的一个萨尔马提亚时期(公元2 - 3世纪)的储存坑中发现的一例结核性脑膜炎病例
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-12 DOI: 10.1016/j.tube.2025.102632
Ágota Madai , Marcos De Andrés Montero , Luca Kis , Csaba Szalontai , Anna Szigeti , István Major , Attila Kiss P. , Olga Spekker
The aim of our paper is to demonstrate a case (KD429) with tuberculous meningitis (TBM) from the 2nd–3rd‒century‒CE Carpathian Basin. The skeleton of KD429 was subject to a detailed macromorphological evaluation, focusing on the detection of pathological lesions likely related to tuberculosis (TB). It was the presence of endocranial alterations, especially the TB-specific granular impressions, based on which the diagnosis of TBM was established in KD429. Besides KD429, only eight cases with TB have been published from the Sarmatian-period (1st–5th centuries CE) Carpathian Basin. Reports of archaeological cases with TB, like KD429, can provide invaluable information about the spatio-temporal distribution of the disease in the past. Nonetheless, to get a more accurate picture about the burden that TB may have put on the Sarmatians, the systematic macromorphological (re-)evaluation of their osteoarchaeological series would be advantageous. Interestingly, the skeleton of KD429 was unearthed from not a grave-pit but a storage pit from the archaeological site of Kiskundorozsma–Daruhalom-dűlő II (Hungary). At the current state of research, the motive behind the exclusion of KD429 from the “normal” burial custom cannot be determined; therefore, it remains an open question whether their disease (TBM) played a role in it or not.
我们的论文的目的是证明一个病例(KD429)结核性脑膜炎(TBM)来自公元2 - 3世纪的喀尔巴阡盆地。对KD429的骨骼进行了详细的宏观形态学评估,重点是检测可能与结核病(TB)相关的病理病变。正是颅内改变的存在,特别是结核病特异性颗粒印象,在KD429中建立了TBM的诊断。除KD429外,萨尔马时期(公元1 - 5世纪)喀尔巴阡盆地仅报告了8例结核病例。关于结核病考古病例的报告,如KD429,可以提供有关该疾病过去时空分布的宝贵信息。尽管如此,为了更准确地了解结核病可能给萨尔马特人带来的负担,对他们的骨考古系列进行系统的宏观形态学(重新)评估将是有利的。有趣的是,KD429的骨架不是从坟墓中出土的,而是从Kiskundorozsma-Daruhalom-dűlő II(匈牙利)考古遗址的一个储存坑中出土的。在目前的研究状态下,无法确定将KD429排除在“正常”丧葬习俗之外的动机;因此,他们的疾病(TBM)是否在其中起作用仍然是一个悬而未决的问题。
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引用次数: 0
Dry powder Inhalation of lytic mycobacteriophages for adjunct therapy in a mouse model of infection with Mycobacterium tuberculosis 干粉吸入溶解性分枝杆菌噬菌体辅助治疗结核分枝杆菌感染小鼠模型
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-11 DOI: 10.1016/j.tube.2025.102631
Sunil K. Raman , Trisha Roy , Khushboo Verma , Chunna Yadav , Sonia Verma , Venkata Siva Reddy Deivreddy , Hasham Shafi Sofi , Reena Bharti , Rahul Sharma , Himanshu Bansode , Akhilesh Kumar , Rakesh Kumar Sharma , Jyotsna Singh , Madhav N. Mugale , Urmi Bajpai , Vikas Jain , Amit Kumar Singh , Amit Misra
Inhaled therapy of tuberculosis (TB) by a Dry Powder Inhalation (DPI) comprising mycobacteriophage D29 and TM4 was non-inferior to oral anti-tuberculosis therapy (ATT) with isoniazid and rifampicin in a mouse model of infection with Mycobacterium tuberculosis (Mtb). No pharmaceutical phage product of mycobacteriophages is approved for large-scale production. We scaled up preparation and downstream processing of phages, developed DPI formulations, and established methods for determining identity, purity, assay, stability, and critical quality attributes (CQA). We carried out cell-based assays of intracellular bactericidal activity and pharmacokinetics and comparative efficacy in Mtb-infected mice. Daily doses of the DPI containing ∼1010 Plaque Forming Units/dose DPI reduced Mtb colony forming units (CFU) in the lungs from 6.4 ± 0.3-log to 4.8 ± 0.7-log in four weeks, while oral human equivalent doses (HED) of isoniazid and rifampicin reduced CFU to 3.8 ± 0.8-log. Combining inhaled phages with oral drugs sterilized the lungs of one of four mice and reduced group mean CFU to 2.3-log. Inhalations significantly upregulated tumor necrosis factor (TNF) in lung tissue to ∼1500 pg/ml of homogenate, improved organ morphology, and reduced histopathology. The HD DPI may be a useful adjunct to oral drugs. Dose-finding animal efficacy studies are required before assessing preclinical safety.
在感染结核分枝杆菌(Mtb)的小鼠模型中,用含有分枝杆菌噬菌体D29和TM4的干粉吸入(DPI)治疗结核(TB)的效果不逊于用异烟肼和利福平口服抗结核治疗(ATT)。没有一种药物噬菌体产品被批准大规模生产。我们扩大了噬菌体的制备和下游加工,开发了DPI配方,并建立了鉴定、纯度、测定、稳定性和关键质量属性(CQA)的方法。我们对mtb感染小鼠的细胞内杀菌活性、药代动力学和比较功效进行了基于细胞的测定。每日剂量含有1010个斑块形成单位/剂量的DPI在四周内将肺中的结核菌落形成单位(CFU)从6.4±0.3 log降低到4.8±0.7 log,而口服异烟肼和利福平的人等效剂量(HED)将CFU降低到3.8±0.8 log。将吸入噬菌体与口服药物联合使用,对4只小鼠中的1只进行肺消毒,使组平均CFU降至2.3 log。吸入显著上调肺组织中的肿瘤坏死因子(TNF)至~ 1500 pg/ml匀浆,改善器官形态,减少组织病理学。HD DPI可能是口服药物的有用辅助。在评估临床前安全性之前,需要进行剂量性动物疗效研究。
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引用次数: 0
A snapshot of genomic diversity and transmission clusters of rifampin-resistant Mycobacterium tuberculosis complex in the Central African Republic 中非共和国耐利福平结核分枝杆菌复合体基因组多样性和传播集群的快照
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-03-07 DOI: 10.1016/j.tube.2025.102627
B. Jolly , J. Saad , A. Farra , A. Manirakiza , G. Zandanga , E. Nakoune , Y. Boum II , E. Gando , G. Grine , C. Mossoro-Kpinde , M. Drancourt
Tuberculosis, a significant public health concern in Central African Republic lacks whole-genome-based identification and typing of the Mycobacterium tuberculosis complex strains circulating in populations in that country. Here, we investigated 68 rifampin-resistant clinical isolates collected in 2024 from eight districts in Bangui and surrounding regions. The analysis revealed that all isolates were M. tuberculosis stricto sensu, distributed across nine lineages: L4.1.2.1 Haarlem (n = 20), L4.6 Euro-American (n = 17), L4.6.1.2 Uganda (n = 13), L4.6.2.2 Cameroon (n = 12), and L4.1.1.1 X-Type (n = 2), and single isolates in L4.1 (Euro-American), L4.6.1 (Uganda), L4.3.1 (LAM), and L3 (Delhi-CAS). The antibiotic resistance profile showed that 9/68 (13.2 %) of the M. tuberculosis isolates were susceptible, while 59/68 (86.7 %) exhibited at least one predicted antibiotic resistance. These data provide new insights into tuberculosis transmission in Central African Republic in contrast to reports from neighboring countries, including the absence of Mycobacterium bovis, hence zoonotic tuberculosis and other factors. This preliminary study limited to rifampin-resistant isolates, nevertheless paves the way for a genome-based survey of tuberculosis in Central African Republic which is essential for enhancing the management and control of the deadly tuberculosis that is a public health concern in the country.
结核病是中非共和国的一个重大公共卫生问题,缺乏对该国人群中流行的结核分枝杆菌复合菌株的全基因组鉴定和分型。在这里,我们调查了2024年从班吉8个区及周边地区收集的68株利福平耐药临床分离株。所有分离株均为严格感结核分枝杆菌,分布在9个谱系:L4.1.2.1 Haarlem (n = 20)、L4.6欧美(n = 17)、L4.6.1.2乌干达(n = 13)、L4.6.2.2喀麦隆(n = 12)和L4.1.1.1 x型(n = 2), L4.1欧美、L4.6.1乌干达、L4.3.1 LAM和L3德里- cas。耐药谱显示,9/68株(13.2%)结核分枝杆菌敏感,59/68株(86.7%)至少表现出一种预测耐药。与邻国的报告相比,这些数据为中非共和国的结核病传播提供了新的见解,包括没有牛分枝杆菌,因此没有人畜共患结核病和其他因素。然而,这项初步研究仅限于对利福平耐药的分离株,为中非共和国开展基于基因组的结核病调查铺平了道路,这对于加强对致命结核病的管理和控制至关重要,结核病是该国的一个公共卫生问题。
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引用次数: 0
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Tuberculosis
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