摘要

上个世纪抗生素的广泛使用导致抗生素抗性病原体发生显着的人为选择压力。引入了各种对抗这些病原体的策略，包括新抗生素，特异性针对病原体的天然衍生酶/肽和溶解这些病原体的噬菌体。最近推出了一种新的工具，用于抗击耐药病原体 - 原核生物防御机制 - 聚集成规则的间隔短回文重复序列-CRISPR相关（CRISPR-Cas）系统。 CRISPR-Cas系统作为一种核酸酶，可被引导切割任何目标DNA，从而实现复杂而可行的病原体操作。在这里，我们回顾了使用CRISPR-Cas系统特异性编辑细菌种群，消除其抗性基因并将这两种策略结合起来以便为抗生素敏感病原体产生人为选择压力的开创性研究。我们建议，该系统的智能设计，以及有效的病原体传递工具，可以显着降低耐抗生素病原体的威胁。

The extensive use of antibiotics over the last century has resulted in a significant artificial selection pressure for antibiotic-resistant pathogens to evolve. Various strategies to fight these pathogens have been introduced including new antibiotics, naturally-derived enzymes/peptides that specifically target pathogens and bacteriophages that lyse these pathogens. A new tool has recently been introduced in the fight against drug-resistantpathogens–the prokaryotic defense mechanism–clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system. The CRISPR-Cas system acts as a nuclease that can be guided to cleave any target DNA, allowing sophisticated, yet feasible, manipulations of pathogens. Here, we review pioneering studies that use the CRISPR-Cas system to specifically edit bacterial populations, eliminate their resistance genes and combine these two strategies in order to produce an artificial selection pressure for antibiotic-sensitive pathogens. We suggest that intelligent design of this system, along with efficient delivery tools into pathogens, may significantly reduce the threat of antibiotic-resistant pathogens.

https://www.sciencedirect.com/science/article/pii/S1368764616300577