Tobin David M, Ramakrishnan Lalita
Department of Microbiology, University of Washington, Seattle, WA, USA.
Cell Microbiol. 2008 May;10(5):1027-39. doi: 10.1111/j.1462-5822.2008.01133.x. Epub 2008 Feb 20.
A thorough understanding of Mycobacterium tuberculosis pathogenesis in humans has been elusive in part because of imperfect surrogate laboratory hosts, each with its own idiosyncrasies. Mycobacterium marinum is the closest genetic relative of the M. tuberculosis complex and is a natural pathogen of ectotherms. In this review, we present evidence that the similar genetic programmes of M. marinum and M. tuberculosis and the corresponding host immune responses reveal a conserved skeleton of Mycobacterium host-pathogen interactions. While both species have made niche-specific refinements, an essential framework has persisted. We highlight genetic comparisons of the two organisms and studies of M. marinum in the developing zebrafish. By pairing M. marinum with the simplified immune system of zebrafish embryos, many of the defining mechanisms of mycobacterial pathogenesis can be distilled and investigated in a tractable host/pathogen pair.
由于缺乏理想的替代实验室宿主，每种宿主都有其自身的特性，因此对结核分枝杆菌在人类中的发病机制的全面理解一直难以实现。海分枝杆菌是结核分枝杆菌复合群中亲缘关系最近的基因亲属，是变温动物的天然病原体。在这篇综述中，我们提供的证据表明，海分枝杆菌和结核分枝杆菌相似的基因程序以及相应的宿主免疫反应揭示了分枝杆菌宿主-病原体相互作用的保守框架。虽然这两个物种都进行了特定生态位的优化，但一个基本框架仍然存在。我们着重介绍了这两种生物的基因比较以及在发育中的斑马鱼中对海分枝杆菌的研究。通过将海分枝杆菌与斑马鱼胚胎简化的免疫系统配对，可以在一个易于处理的宿主/病原体组合中提炼并研究分枝杆菌发病机制的许多决定性机制。
