A central challenge in infection medicine is to determine the structure and function of host–pathogen protein–protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host–pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial–human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and -tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs.

中文翻译：

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细菌-人类蛋白质相互作用中的结构蛋白质组学，电子冷冻显微镜和结构建模方法。

感染医学的一个主要挑战是确定宿主-病原体蛋白-蛋白相互作用的结构和功能，以了解这些相互作用如何促进细菌粘附，传播和存活。在这篇综述中，我们重点关注蛋白质组学，电子冷冻显微镜和结构建模，以展示亲和纯化（AP）和交联（XL）质谱（MS）增进了我们对宿主-病原体相互作用的理解的实例。我们重点介绍了XL-MS与结构建模相结合的案例，这些案例提供了对种间蛋白质复合物四级结构的了解。我们进一步举例说明了如何使用电子冷冻断层扫描技术来可视化附着和感染过程中细菌与人的相互作用。最后，我们讨论AP-MS如何 XL-MS和电子冷冻显微镜和断层扫描以及结构建模方法可用于未来的研究，以拓宽我们对此类相互作用的功能，动力学和演变的认识。这些知识将与未来的药物和疫苗开发计划相关。