PDF(Pubmed)
Abstract：
The spread of multi-drug-resistant (MDR) pathogens has rapidly outpaced the development of effective treatments. Diverse resistance mechanisms further limit the effectiveness of our best treatments, including multi-drug regimens and last line-of-defense antimicrobials. Biofilm formation is a powerful component of microbial pathogenesis, providing a scaffold for efficient colonization and shielding against anti-microbials, which further complicates drug resistance studies. Early genetic knockout tools didn\'t allow the study of essential genes, but clustered regularly interspaced palindromic repeat inference (CRISPRi) technologies have overcome this challenge via genetic silencing. These tools rapidly evolved to meet new demands and exploit native CRISPR systems. Modern tools range from the creation of massive CRISPRi libraries to tunable modulation of gene expression with CRISPR activation (CRISPRa). This review discusses the rapid expansion of CRISPRi/a-based technologies, their use in investigating MDR and biofilm formation, and how this drives further development of a potent tool to comprehensively examine multi-drug resistance.
摘要：
多药耐药（MDR）病原体的传播迅速超过了有效治疗的发展。不同的抗性机制进一步限制了我们最佳治疗方法的有效性，包括多药方案和最后一道防线抗菌药物。生物膜形成是微生物发病机制的有力组成部分,提供有效定殖和屏蔽抗微生物剂的支架，这进一步使耐药性研究复杂化。早期的基因敲除工具不允许研究必需基因，但是聚集的规则间隔回文重复推理（CRISPRi）技术已经通过遗传沉默克服了这一挑战。这些工具迅速发展以满足新的需求并利用本地CRISPR系统。现代工具的范围从创建大规模CRISPRi文库到用CRISPR激活(CRISPRa)可调调节基因表达。这篇综述讨论了基于CRISPRi/a的技术的快速扩展，它们在研究MDR和生物膜形成中的用途，以及这如何推动全面检查多药耐药性的有力工具的进一步发展。
