To date, antibiotics have been identified on the basis of their ability to kill bacteria or inhibit their growth rather than directly for their capacity to improve clinical outcomes of infected patients. Although historically successful, this approach has led to the development of an antibiotic armamentarium that suffers from a number of shortcomings, including the inevitable emergence of resistance and, in certain infections, suboptimal efficacy leading to long treatment durations, infection recurrence, or high mortality and morbidity rates despite apparent bacterial sterilization. Conventional antibiotics fail to address the complexities of in vivo bacterial physiology and virulence, as well as the role of the host underlying the complex, dynamic interactions that cause disease. New interventions are needed, aimed at host outcome rather than microbiological cure. Here we review the role of screening models for cellular and whole-organism infection, including worms, flies, zebrafish, and mice, to identify novel therapeutic strategies and discuss their future implications.

迄今为止，抗生素的鉴定基于其杀死细菌或抑制其生长的能力，而不是直接基于其改善感染患者临床结果的能力。虽然在历史上是成功的，但这种方法导致了抗生素装备的开发，但它有许多缺点，包括不可避免地出现耐药性，以及在某些感染中，疗效不佳导致治疗持续时间长、感染复发或死亡率高，以及尽管有明显的细菌灭菌，但发病率仍然很高。传统抗生素无法解决体内细菌生理学和毒力的复杂性，以及宿主在导致疾病的复杂、动态相互作用背后的作用。需要新的干预措施，旨在宿主结果而不是微生物治愈。在这里，我们回顾了细胞和整个生物体感染（包括蠕虫、苍蝇、斑马鱼和小鼠）筛选模型的作用，以确定新的治疗策略并讨论它们的未来意义。