Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Animal Care and Veterinary Service, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
STAR Protoc. 2022 Jul 19;3(3):101575. doi: 10.1016/j.xpro.2022.101575. eCollection 2022 Sep 16.
Available mouse models for tuberculosis drug susceptibility testing requires using virulent biosafety-level-3 (BSL-3) (Mtb) strains, or attenuated BSL-2 strains that lack virulence genes. Here, we present a BSL-2-compatible mouse model for tuberculosis drug susceptibility testing using the auxotrophic Mtb mc6206 strain, which retains all virulence genes. Using rifampicin and a new autophagy-boosting compound, SMIP-30, we provide a step-by-step guide for the infection, drug administration, and evaluation of Mtb burden and cytokine profiles. This protocol is easily adaptable for testing of other antibiotics and host-directed compounds. For complete details on the use and execution of this protocol, please refer to Berton et al. (2022).
用于结核病药物敏感性测试的可用小鼠模型需要使用高致病性生物安全级别 3（BSL-3）（结核分枝杆菌）菌株，或缺乏毒力基因的减毒 BSL-2 菌株。在这里，我们使用营养缺陷型 Mtb mc6206 菌株（保留所有毒力基因）介绍了一种用于结核病药物敏感性测试的 BSL-2 相容的小鼠模型。使用利福平（rifampicin）和一种新的自噬增强化合物 SMIP-30，我们为感染、药物给药以及 Mtb 负荷和细胞因子谱的评估提供了逐步指南。该方案易于适应其他抗生素和宿主导向化合物的测试。有关该方案的使用和执行的完整详细信息，请参阅 Berton 等人（2022 年）。
