Department of Microbiology and Immunology, College of Medicine, University of Louisville, KY, USA.
Department of Microbiology and Immunology, College of Medicine, University of Louisville, KY, USA; Center for Predictive Medicine, College of Medicine, University of Louisville, KY, USA.
Trends Microbiol. 2019 Jun;27(6):550-561. doi: 10.1016/j.tim.2018.12.012. Epub 2019 Jan 14.
The host is a nutrient-rich niche for microbial pathogens, but one that comes with obstacles and challenges. Many intracellular pathogens like Legionella pneumophila, Coxiella burnetii, Listeria monocytogenes, and Chlamydia trachomatis have developed bipartite metabolism within their hosts. This style of metabolic regulation enables pathogen sensing of specific nutrients to engage them into catabolic and anabolic processes, and contributes to temporal and spatial pathogen phenotypic modulation. Not only have intracellular pathogens adapted their metabolism to the host, they have also acquired idiosyncratic strategies to exploit host nutritional supplies and intercept metabolites. Francisella tularensis and Anaplasma phagocytophilum alter host autophagy, Shigella flexneri intercepts all host pyruvate, while L. pneumophila induces host protein degradation and blocks protein translation. Strategies of pathogen manipulation of host nutrients could serve as therapeutic targets.
宿主是微生物病原体的营养丰富小生境,但也伴随着障碍和挑战。许多细胞内病原体,如嗜肺军团菌、贝氏柯克斯体、李斯特菌和沙眼衣原体,在宿主中已经发展出二分代谢。这种代谢调节方式使病原体能够感应特定的营养物质,从而使它们参与分解代谢和合成代谢过程,并有助于病原体表型的时间和空间调节。细胞内病原体不仅使它们的代谢适应了宿主,还获得了独特的策略来利用宿主的营养供应和拦截代谢物。土拉弗朗西斯菌和嗜吞噬细胞无形体改变宿主自噬,福氏志贺菌拦截所有宿主丙酮酸,而嗜肺军团菌则诱导宿主蛋白降解并阻断蛋白翻译。病原体对宿主营养物质的操纵策略可以作为治疗靶点。