Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
J Nanobiotechnology. 2021 Dec 4;19(1):401. doi: 10.1186/s12951-021-01132-8.
Antibiotic resistance is spreading rapidly around the world and seriously impeding efforts to control microbial infections. Although nucleic acid testing is widely deployed for the detection of antibiotic resistant bacteria, the current techniques-mainly based on polymerase chain reaction (PCR)-are time-consuming and laborious. There is an urgent need to develop new strategies to control bacterial infections and the spread of antimicrobial resistance (AMR). The CRISPR-Cas system is an adaptive immune system found in many prokaryotes that presents attractive opportunities to target and edit nucleic acids with high precision and reliability. Engineered CRISPR-Cas systems are reported to effectively kill bacteria or even revert bacterial resistance to antibiotics (resensitizing bacterial cells to antibiotics). Strategies for combating antimicrobial resistance using CRISPR (i.e., Cas9, Cas12, Cas13, and Cas14) can be of great significance in detecting bacteria and their resistance to antibiotics. This review discusses the structures, mechanisms, and detection methods of CRISPR-Cas systems and how these systems can be engineered for the rapid and reliable detection of bacteria using various approaches, with a particular focus on nanoparticles. In addition, we summarize the most recent advances in applying the CRISPR-Cas system for virulence modulation of bacterial infections and combating antimicrobial resistance.
抗生素耐药性正在全球范围内迅速传播,严重阻碍了控制微生物感染的努力。尽管核酸检测被广泛用于检测抗生素耐药菌,但目前的技术——主要基于聚合酶链反应(PCR)——既耗时又费力。因此,迫切需要开发新的策略来控制细菌感染和抗生素耐药性(AMR)的传播。CRISPR-Cas 系统是一种存在于许多原核生物中的适应性免疫系统,为靶向和编辑核酸提供了高精确度和高可靠性的诱人机会。已报道工程化的 CRISPR-Cas 系统可有效杀死细菌,甚至使细菌对抗生素的耐药性逆转(使细菌细胞对抗生素重新敏感)。利用 CRISPR(即 Cas9、Cas12、Cas13 和 Cas14)对抗抗生素耐药性的策略在检测细菌及其对抗生素的耐药性方面具有重要意义。本综述讨论了 CRISPR-Cas 系统的结构、机制和检测方法,以及如何通过各种方法(特别关注纳米颗粒)对这些系统进行工程化,以实现细菌的快速可靠检测。此外,我们总结了最近在利用 CRISPR-Cas 系统调节细菌感染的毒力和对抗抗生素耐药性方面的最新进展。