Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, UK.
Department of Pathology, Animal and Plant Health Agency, Addlestone, UK.
Virulence. 2022 Dec;13(1):1543-1557. doi: 10.1080/21505594.2022.2119657.
Tuberculosis (TB), caused by (), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here, we demonstrate and present a basic description of how (the greater wax moth, ) larvae can be used as a low cost, rapid, and ethically more acceptable model for TB research. This is the first study to infect with the fully virulent H37Rv, the most widely used strain in research. Infection of with resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated BCG and auxotrophic strains. The model can also be used for anti-TB drug screening, although CFU enumeration from is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of isogenic mutants can be determined in . However, comparison of mutant phenotypes in against conventional models must consider the limitations of innate immunity. Our findings indicate that will be a practical, valuable, and advantageous additional model to be used alongside existing models to advance tuberculosis research.
结核病(TB)由()引起,是导致传染病死亡的主要原因。动物感染模型为我们了解结核病做出了重大贡献,但它们的生物学和非生物学限制是研究的瓶颈。需要更多符合伦理、经济和可重复的结核病感染模型,能够模拟疾病的关键方面。在这里,我们展示并介绍了如何使用(大蜡螟幼虫)作为一种低成本、快速且在伦理上更可接受的结核病研究模型的基本描述。这是首次使用完全毒力的 H37Rv(在研究中使用最广泛的菌株)感染的研究。用 感染 导致了有症状的致死性感染,其毒力与减毒的 BCG 和营养缺陷型菌株不同。该模型也可用于抗结核药物筛选,尽管需要从 中进行 CFU 计数以确认测试化合物对减少分枝杆菌负荷的活性。此外,可以在 中确定 的同源突变体的比较毒力。然而,在 中比较突变体表型与传统模型相比,必须考虑到先天免疫的局限性。我们的研究结果表明,将成为一种实用、有价值和有利的附加模型,与现有模型一起用于推进结核病研究。