Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Drug Resist Updat. 2017 Jan;30:1-6. doi: 10.1016/j.drup.2016.11.001. Epub 2016 Nov 27.
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.
上个世纪抗生素的广泛使用导致了抗生素耐药病原体的进化，产生了显著的人工选择压力。为了对抗这些病原体，已经引入了各种策略，包括新型抗生素、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，一种新的工具在对抗耐药病原体的斗争中被引入——原核防御机制——成簇规律间隔短回文重复序列-相关的（CRISPR-Cas）系统。CRISPR-Cas 系统作为一种核酸内切酶，可以被引导切割任何靶 DNA，从而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 系统来特异性编辑细菌群体、消除其耐药基因并将这两种策略结合起来以产生抗生素敏感病原体的人工选择压力的开创性研究。我们认为，该系统的智能设计以及将有效工具递送到病原体中，可能会显著降低抗生素耐药病原体的威胁。
