Rabaan Ali A, Al Fares Mona A, Almaghaslah Manar, Alpakistany Tariq, Al Kaabi Nawal A, Alshamrani Saleh A, Alshehri Ahmad A, Almazni Ibrahim Abdullah, Saif Ahmed, Hakami Abdulrahim R, Khamis Faryal, Alfaresi Mubarak, Alsalem Zainab, Alsoliabi Zainab A, Al Amri Kawthar Amur Salim, Hassoueh Amal K, Mohapatra Ranjan K, Arteaga-Livias Kovy, Alissa Mohammed
Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Microorganisms. 2023 Sep 26;11(10):2404. doi: 10.3390/microorganisms11102404.
Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.
据估计,被称为超级细菌的菌株中的多药耐药性在全球范围内导致致命感染。迁移和城市化导致过度拥挤和卫生条件不足,增加了不同社区内部和之间超级细菌感染的高风险。CRISPR-Cas系统,主要是II型,已被视为一种强大的工具,可精确编辑耐药细菌基因组,以有效对抗抗生素耐药细菌菌株。为了充分发挥其潜力,需要在CRISPR-Cas系统方面进行进一步开发,以降低毒性并提高基因编辑应用的功效。这可能涉及用于产生点突变的碱基编辑技术。这些方法采用设计好的Cas9变体,如腺嘌呤碱基编辑器(ABE)和胞嘧啶碱基编辑器(CBE),直接编辑单碱基对而不引起双链断裂。CBE和ABE可以将目标碱基对改变为另一个(例如,G-C变为A-T或C-G变为A-T)。在本综述中,我们阐述了CRISPR/Cas系统的局限性,并探索了通过应用各种碱基编辑技术来规避这些局限性的策略。此外,我们还讨论了最近展示碱基编辑器消除耐药微生物能力的研究。