St Louis Brendyn M, Quagliato Sydney M, Lee Pei-Chung
Department of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI, United States.
Front Microbiol. 2023 Feb 10;14:1113021. doi: 10.3389/fmicb.2023.1113021. eCollection 2023.
Post-translational modifications (PTMs) are critical in regulating protein function by altering chemical characteristics of proteins. Phosphorylation is an integral PTM, catalyzed by kinases and reversibly removed by phosphatases, that modulates many cellular processes in response to stimuli in all living organisms. Consequently, bacterial pathogens have evolved to secrete effectors capable of manipulating host phosphorylation pathways as a common infection strategy. Given the importance of protein phosphorylation in infection, recent advances in sequence and structural homology search have significantly expanded the discovery of a multitude of bacterial effectors with kinase activity in pathogenic bacteria. Although challenges exist due to complexity of phosphorylation networks in host cells and transient interactions between kinases and substrates, approaches are continuously being developed and applied to identify bacterial effector kinases and their host substrates. In this review, we illustrate the importance of exploiting phosphorylation in host cells by bacterial pathogens the action of effector kinases and how these effector kinases contribute to virulence through the manipulation of diverse host signaling pathways. We also highlight recent developments in the identification of bacterial effector kinases and a variety of techniques to characterize kinase-substrate interactions in host cells. Identification of host substrates provides new insights for regulation of host signaling during microbial infection and may serve as foundation for developing interventions to treat infection by blocking the activity of secreted effector kinases.
翻译后修饰（PTMs）通过改变蛋白质的化学特性在调节蛋白质功能方面起着关键作用。磷酸化是一种不可或缺的翻译后修饰，由激酶催化，并可被磷酸酶可逆性去除，它能调节所有生物体中许多细胞过程以响应刺激。因此，细菌病原体已经进化出分泌能够操纵宿主磷酸化途径的效应蛋白，作为一种常见的感染策略。鉴于蛋白质磷酸化在感染中的重要性，序列和结构同源性搜索方面的最新进展显著扩大了对病原菌中多种具有激酶活性的细菌效应蛋白的发现。尽管由于宿主细胞中磷酸化网络的复杂性以及激酶与底物之间的瞬时相互作用而存在挑战，但仍在不断开发和应用各种方法来鉴定细菌效应激酶及其宿主底物。在这篇综述中，我们阐述了细菌病原体利用宿主细胞磷酸化的重要性、效应激酶的作用以及这些效应激酶如何通过操纵多种宿主信号通路来促进毒力。我们还强调了在鉴定细菌效应激酶方面的最新进展以及用于表征宿主细胞中激酶 - 底物相互作用的各种技术。鉴定宿主底物为微生物感染期间宿主信号调节提供了新的见解，并可能为通过阻断分泌的效应激酶活性来开发治疗感染的干预措施奠定基础。
