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-resistant pathogens–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.

上个世纪以来，抗生素的广泛使用给抗生素耐药性病原体的进化带来了巨大的人工选择压力。已经提出了与这些病原体作斗争的各种策略，包括新的抗生素，专门针对病原体的天然来源的酶/肽和裂解这些病原体的噬菌体。最近，在抗药性病原体的对抗中引入了一种新工具-原核防御机制-聚簇的规则间隔的短回文重复序列-CRISPR相关（CRISPR-Cas）系统。CRISPR-Cas系统充当核酸酶，可被引导以切割任何目标DNA，从而允许对病原体进行复杂但可行的操作。在这里，我们回顾了使用CRISPR-Cas系统专门编辑细菌种群的开创性研究，消除它们的抗性基因，并结合这两种策略，以对抗生素敏感的病原体产生人为的选择压力。我们建议，该系统的智能设计以及向病原体的有效输送工具，可以显着减少对抗生素耐药的病原体的威胁。