Humanity’s ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host–pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host–bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.

人类与新的、重新出现的地方性传染病的持续斗争经常提醒人们需要了解宿主-病原体的相互作用。基因组学的最新进展极大地促进了我们对遗传学如何促成宿主抗性或对细菌感染的易感性的理解。在这里，我们讨论了在全基因组水平上定义宿主-细菌相互作用的当前趋势，包括利用 CRISPR/Cas9 基因组编辑、自然遗传变异、蛋白质组学和转录组学的筛选。我们报告了这些创新筛选的优点、局限性和发现，并讨论了它们的互补性。最后，随着我们在后基因组时代的不断进步以及更深入的机制洞察和临床应用，我们推测未来的创新。