Program Infection and Immunity, Fundación Caubet-CIMERA Illes Balears, Recinto Hospital Joan March, Carretera Soller Km 12, 07110 Bunyola, Spain. Area Molecular basis of microbial pathogenesis, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES) Bunyola, Spain. Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Environ Microbiol Rep. 2010 Apr;2(2):219-27. doi: 10.1111/j.1758-2229.2009.00068.x. Epub 2009 Aug 19.
Infectious diseases are a leading cause of global human mortality. The use of antimicrobials remains the most common strategy for treatment. However, the isolation of pathogens resistant to virtually all antimicrobials makes it urgent to develop effective therapeutics based on new targets. Here we review a new drug discovery paradigm focusing on identifying and targeting host factors important for infection as well as pathogen determinants involved in disease progression. We summarize innovative strategies which by combining bioinformatics with transcriptomics and chemical genetics have already identified host factors essential for pathogen entry, survival and replication. We describe how the discovery of RNA interference which allows loss-of-function studies has facilitated functional genomic studies in human cells. It is expected that these studies will identify targets to be used as host-directed drug therapy which, together with antimicrobials targeting microbial virulence factors, will efficiently eliminate the invading pathogen.
传染病是全球人类死亡的主要原因。使用抗生素仍然是治疗的最常见策略。然而，几乎所有抗生素都产生抗药性的病原体的分离，使得基于新靶点开发有效治疗方法变得紧迫。在这里，我们回顾了一种新的药物发现范例，重点是确定和针对感染宿主因素以及参与疾病进展的病原体决定因素。我们总结了一些创新策略，这些策略通过将生物信息学与转录组学和化学遗传学相结合，已经确定了病原体进入、存活和复制所必需的宿主因素。我们描述了 RNA 干扰的发现如何促进了人类细胞中的功能基因组研究，RNA 干扰允许进行功能丧失研究。预计这些研究将确定可作为宿主定向药物治疗的靶点，这些靶点与针对微生物毒力因子的抗生素一起，将有效地消除入侵的病原体。
