Schwegmann Anita, Brombacher Frank
Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town and The International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.
Sci Signal. 2008 Jul 22;1(29):re8. doi: 10.1126/scisignal.129re8.
The current paradigm for managing infectious diseases has targeted unique processes or enzymes within pathogens. A serious disadvantage of this pathogen-directed drug targeting strategy has been the development of microbial drug resistance and consequent resurgence of once-contained infectious diseases. A new drug discovery paradigm has therefore emerged focusing on identifying and targeting host factors essential for pathogen entry, survival, and replication. Innovative strategies combining genome-wide computational biology, genomics, proteomics, and traditional forward and reverse genetics have identified host-pathogen interactions and host functions critical for the establishment of infection. Chemogenomics and chemical genetics have allowed rapid identification of new and existing licensed drugs with antimicrobial activity. Although most host-directed drug targeting studies have focused on viral infections, they have provided a proof of concept for similar approaches to bacterial and parasite infections. Future therapies may combine conventional targeting of microbial virulence factors, together with host-directed drug therapy and augmentation of protective host factors, to efficiently eliminate the invading pathogen.
当前管理传染病的模式一直以病原体内部独特的过程或酶为目标。这种针对病原体的药物靶向策略的一个严重缺点是微生物耐药性的发展以及曾经得到控制的传染病随之死灰复燃。因此，一种新的药物发现模式应运而生，其重点在于识别和靶向病原体进入、存活及复制所必需的宿主因子。结合全基因组计算生物学、基因组学、蛋白质组学以及传统正向和反向遗传学的创新策略已经确定了对感染建立至关重要的宿主-病原体相互作用和宿主功能。化学基因组学和化学遗传学使得能够快速识别具有抗菌活性的新的和现有的已获许可药物。尽管大多数针对宿主的药物靶向研究都集中在病毒感染上，但它们为针对细菌和寄生虫感染的类似方法提供了概念验证。未来的治疗方法可能会将传统的针对微生物毒力因子的靶向与针对宿主的药物治疗以及增强保护性宿主因子相结合，以有效消除入侵的病原体。
