Design and in situ biosynthesis of precision therapies against gastrointestinal pathogens
Design and in situ biosynthesis of precision therapies against gastrointestinal pathogens
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DOI：
10.1016/j.cophys.2021.06.007
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发表时间：
2021-07-24
影响因子：
2.5
通讯作者：
Crook, Nathan C.
中科院分区：
文献类型：
--
作者：
Durmusoglu, Deniz;Catella, Carly M.;Crook, Nathan C.
胃肠道病原体采用多种机制破坏宿主组织，获取营养，并逃避治疗。为了补充广谱抗菌剂，人们越来越感兴趣的是设计靶向特定分类群和毒力过程的分子。令人兴奋的是，这些抗病毒疗法可能能够由肠道驻留微生物合成，从而使这些药物能够直接递送到感染的空间和时间部位。在这篇综述中，我们强调了最近的进展，我们的理解小分子抑制特定的毒力机制。我们还讨论了新兴的方法来发现病原体特异性和机制特异性肽和小蛋白。最后，我们涵盖了最近的益生菌工程生产抗菌剂，以响应肠道中的病原体特异性线索的示范。总的来说，这些进展指向一种新兴的综合方法来治疗胃肠道疾病，包括微生物学家，肽化学家和合成生物学家。
Gastrointestinal pathogens employ a variety of mechanisms to damage host tissue, acquire nutrients, and evade treatment. To supplement broad-spectrum antimicrobials, there has been increasing interest in designing molecules that target specific taxa and virulence processes. Excitingly, these antivirulence therapies may be able to be synthesized by gut-resident microbes, thereby enabling delivery of these drugs directly to the spatial and temporal site of infection. In this review, we highlight recent progress in our understanding of small molecules that inhibit specific virulence mechanisms. We additionally discuss emerging methods to discover pathogen specific and mechanism-specific peptides and small proteins. Finally, we cover recent demonstrations of probiotics engineered to produce antimicrobials in response to pathogen specific cues in the gut. Collectively, these advances point to an emerging integrative approach to treatment of gastrointestinal diseases, comprising microbiologists, peptide chemists, and synthetic biologists.