Molecular Immunity Unit, Department of Medicine, LMB-MRC, Cambridge CB2 OQH, UK.
Curr Opin Microbiol. 2020 Apr;54:103-110. doi: 10.1016/j.mib.2020.01.011. Epub 2020 Feb 13.
Thirty years ago Stanley Falkow formulated molecular Koch's postulates as a framework to help dissect the contribution of microbial genes to their pathogenicity (Box 1). Three years later, his advice led me to develop Mycobacterium marinum, a close genetic relative of Mycobacterium tuberculosis, as a model for tuberculosis pathogenesis. Here, I discuss insights into M. tuberculosis pathogenicity from studying M. marinum in the zebrafish, and frame them in terms of molecular Koch's postulates. The highly orchestrated life cycle of M. tuberculosis is achieved in substantial measure not by "traditional" pathogen-exclusive virulence genes acquired along its evolutionary history, but rather by genes that are shared with its environmental ancestors. Together, these genes support its tactics of subterfuge and exploitation to overcome host immunity so as to produce the transmissible disease that ensures the evolutionary survival of this obligate human pathogen.
三十年前，斯坦利·福尔科（Stanley Falkow）提出了分子科赫假设，作为一种帮助剖析微生物基因对其致病性贡献的框架（Box 1）。三年后，他的建议促使我利用与结核分枝杆菌（Mycobacterium tuberculosis）密切相关的海分枝杆菌（Mycobacterium marinum）作为结核发病机制的模型。在这里，我将讨论通过在斑马鱼中研究海分枝杆菌，从而对结核分枝杆菌致病性的深入了解，并根据分子科赫假设对其进行阐述。结核分枝杆菌高度协调的生命周期在很大程度上不是通过其进化过程中获得的“传统”、专性致病菌的毒力基因来实现的，而是通过与环境祖先共享的基因来实现的。这些基因共同支持其欺骗和利用策略，以克服宿主免疫，从而产生可传播的疾病，从而确保这种专性人类病原体的进化生存。
