基于感染的化学筛选揭示了宿主-病原体相互作用。
Infection-based chemical screens uncover host-pathogen interactions.
机构信息
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, United States.
出版信息
Curr Opin Microbiol. 2020 Apr;54:43-50. doi: 10.1016/j.mib.2019.12.003. Epub 2020 Feb 7.
Abstract
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.
摘要
细菌病原体必须抵抗宿主固有免疫才能引起疾病。虽然革兰氏阴性菌具有保护性的外膜，但该膜易受宿主诱导的损伤，使这些病原体变得脆弱。我们开发了一种高通量筛选平台，该平台可识别导致巨噬细胞中沙门氏菌属（Salmonella enterica）病原体死亡的化合物。该平台使与巨噬细胞协同作用以防止病原体存活的化合物的快速发现成为可能，因为大多数命中化合物在标准微生物培养基中不活跃，也不是前药。我们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新的抗感染方法。
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