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一线标准治疗药物对易治或难治性结核病小鼠模型杀菌反应、耐药性产生及治愈的作用。

Contribution of front-line, standard-of-care drugs to bactericidal responses, resistance emergence, and cure in murine models of easy- or hard-to-treat tuberculosis disease.

作者信息

Peroutka-Bigus Nathan, Brooks Elizabeth J, Ramey Michelle E, D'Erasmo Hope, Ernest Jackie P, Bauman Allison A, Woolhiser Lisa K, Savic Radojka M, Lenaerts Anne J, Aldridge Bree B, Sarathy Jansy P, Robertson Gregory T

机构信息

Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.

出版信息

Antimicrob Agents Chemother. 2025 May 7;69(5):e0190124. doi: 10.1128/aac.01901-24. Epub 2025 Mar 26.

DOI:10.1128/aac.01901-24
PMID:40135920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12057366/
Abstract

By assessing the standard-of-care regimen for tuberculosis (TB) in BALB/c and C3HeB/FeJ mice, we demonstrate that rifampin, with or without pyrazinamide, is essential for an effective bactericidal response and suppression of resistance. Potency measurements in an lipid-rich model and a rabbit caseum assay recapitulate the significance of rifampin as a sterilizing agent. These outcomes align with clinical performance, thus emphasizing the value of predictive tools and murine TB models with human-like pathology.

摘要

通过评估BALB/c和C3HeB/FeJ小鼠的结核病标准治疗方案，我们证明，无论有无吡嗪酰胺，利福平对于有效的杀菌反应和耐药性抑制都是必不可少的。在富含脂质的模型和兔酪蛋白试验中的效价测量结果再次证明了利福平作为一种杀菌药物的重要性。这些结果与临床疗效一致，从而强调了具有类似人类病理学特征的预测工具和小鼠结核病模型的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/5e7a0daa6df0/aac.01901-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/daf558b21cb7/aac.01901-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/7bd4de4daa5b/aac.01901-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/5e7a0daa6df0/aac.01901-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/daf558b21cb7/aac.01901-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/7bd4de4daa5b/aac.01901-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23f/12057366/5e7a0daa6df0/aac.01901-24.f003.jpg

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本文引用的文献

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Antimicrob Agents Chemother. 2023 Nov 15;67(11):e0059723. doi: 10.1128/aac.00597-23. Epub 2023 Oct 4.
2
A Novel Tool to Identify Bactericidal Compounds against Vulnerable Targets in Drug-Tolerant M. tuberculosis found in Caseum.一种新型工具，可鉴定干酪样物中耐药物结核分枝杆菌的脆弱靶标中的杀菌化合物。
mBio. 2023 Apr 25;14(2):e0059823. doi: 10.1128/mbio.00598-23. Epub 2023 Apr 5.
3
Radiological and functional evidence of the bronchial spread of tuberculosis: an observational analysis.
影像学和功能证据表明结核病支气管播散：一项观察性分析。
Lancet Microbe. 2021 Oct;2(10):e518-e526. doi: 10.1016/S2666-5247(21)00058-6.
4
Systematic measurement of combination-drug landscapes to predict in vivo treatment outcomes for tuberculosis.系统测量联合用药格局以预测结核病的体内治疗结果。
Cell Syst. 2021 Nov 17;12(11):1046-1063.e7. doi: 10.1016/j.cels.2021.08.004. Epub 2021 Aug 31.
5
Comparative Analysis of Pharmacodynamics in the C3HeB/FeJ Mouse Tuberculosis Model for DprE1 Inhibitors TBA-7371, PBTZ169, and OPC-167832.DprE1 抑制剂 TBA-7371、PBTZ169 和 OPC-167832 在 C3HeB/FeJ 小鼠结核病模型中的药效学比较分析。
Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0058321. doi: 10.1128/AAC.00583-21. Epub 2021 Aug 9.
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