Bacterial pathogens must resist host innate immunity to cause disease. While Gram-negative bacteria have a protective outer membrane, this membrane is subject to host-induced damage that makes these pathogens vulnerable. We developed a high content screening platform that identifies compounds that cause the killing of the bacterial pathogen Salmonella enterica in macrophages. This platform enables the rapid discovery of compounds that work in concert with the macrophage to prevent pathogen survival, as most hit compounds are not active in standard microbiological media and are not pro-drugs. We describe within the platform and the compounds it has found, and consider how they may help us discover new ways to fight infection.

中文翻译：

---

基于感染的化学筛选揭示了宿主-病原体的相互作用。

细菌病原体必须抵抗宿主固有的免疫力才能引起疾病。尽管革兰氏阴性细菌具有保护性外膜，但该膜易受宿主诱导的破坏，使这些病原体易受伤害。我们开发了一个高含量的筛选平台，该平台可识别可杀死巨噬细胞中细菌性病原体沙门氏菌的化合物。该平台可快速发现与巨噬细胞协同作用以阻止病原体存活的化合物，因为大多数命中的化合物在标准微生物培养基中均不具有活性，也不是前药。我们在平台中描述了该平台及其发现的化合物，并考虑了它们如何帮助我们发现对抗感染的新方法。