Antibiotics have vastly improved our quality of life since their discovery and introduction into modern medicine. Yet, widespread use and misuse have compromised the efficacy of these compounds and put our ability to cure infectious diseases in jeopardy. To defend themselves against antibiotics, bacteria have evolved an arsenal of survival strategies. In addition to acquiring mutations and genetic determinants that confer antibiotic resistance, bacteria can respond to environmental cues and adopt reversible phenotypic changes that transiently enhance their ability to survive adverse conditions, including those brought on by antibiotics. These antibiotic tolerant and persistent bacteria, which are prevalent in biofilms and can survive antimicrobial therapy without inheriting resistance, are thought to underlie treatment failure and infection relapse. At infection sites, bacteria encounter a range of signals originating from host immunity and the local microbiota that can induce transcriptomic and metabolic reprogramming. In this review, we will focus on the impact of host factors and microbial interactions on antibiotic tolerance and persistence. We will also outline current efforts in leveraging the knowledge of host-microbe and microbe-microbe interactions in designing therapies that potentiate antibiotic activity and reduce the burden caused by recurrent infections.

自从抗生素被发现并引入现代医学以来，它们极大地改善了我们的生活质量。然而，广泛使用和滥用已经损害了这些化合物的功效，并使我们治愈传染病的能力处于危险之中。为了抵御抗生素，细菌进化出了一系列生存策略。除了获得赋予抗生素抗性的突变和遗传决定因素外，细菌还可以对环境线索做出反应并采用可逆的表型变化，从而暂时增强它们在不利条件下生存的能力，包括抗生素带来的条件。这些抗生素耐受性和持久性细菌普遍存在于生物膜中，可以在抗微生物治疗中存活而不会遗传耐药性，被认为是治疗失败和感染复发的基础。在感染部位，细菌会遇到一系列来自宿主免疫和局部微生物群的信号，这些信号可以诱导转录组和代谢重编程。在这篇综述中，我们将重点关注宿主因素和微生物相互作用对抗生素耐受性和持久性的影响。我们还将概述当前在利用宿主-微生物和微生物-微生物相互作用的知识来设计增强抗生素活性和减少复发性感染负担的疗法方面所做的努力。我们将关注宿主因素和微生物相互作用对抗生素耐受性和持久性的影响。我们还将概述当前在利用宿主-微生物和微生物-微生物相互作用的知识来设计增强抗生素活性和减少复发性感染负担的疗法方面所做的努力。我们将关注宿主因素和微生物相互作用对抗生素耐受性和持久性的影响。我们还将概述当前在利用宿主-微生物和微生物-微生物相互作用的知识来设计增强抗生素活性和减少复发性感染负担的疗法方面所做的努力。