Kadkhoda Hiva, Gholizadeh Pourya, Samadi Kafil Hossein, Ghotaslou Reza, Pirzadeh Tahereh, Ahangarzadeh Rezaee Mohammad, Nabizadeh Edris, Feizi Hadi, Aghazadeh Mohammad
Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Heliyon. 2024 Jul 16;10(14):e34692. doi: 10.1016/j.heliyon.2024.e34692. eCollection 2024 Jul 30.
The emergence and development of antibiotic resistance in bacteria is a serious threat to global public health. Antibiotic resistance genes (ARGs) are often located on mobile genetic elements (MGEs). They can be transferred among bacteria by horizontal gene transfer (HGT), leading to the spread of drug-resistant strains and antibiotic treatment failure. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated genes) is one of the many strategies bacteria have developed under long-term selection pressure to restrict the HGT. CRISPR-Cas systems exist in about half of bacterial genomes and play a significant role in limiting the spread of antibiotic resistance. On the other hand, bacteriophages and other MGEs encode a wide range of anti-CRISPR proteins (Acrs) to counteract the immunity of the CRISPR-Cas system. The Acrs could decrease the CRISPR-Cas system's activity against phages and facilitate the acquisition of ARGs and virulence traits for bacteria. This review aimed to assess the relationship between the CRISPR-Cas systems and Acrs with bacterial antibiotic resistance. We also highlighted the CRISPR technology and Acrs to control and prevent antibacterial resistance. The CRISPR-Cas system can target nucleic acid sequences with high accuracy and reliability; therefore, it has become a novel gene editing and gene therapy tool to prevent the spread of antibiotic resistance. CRISPR-based approaches may pave the way for developing smart antibiotics, which could eliminate multidrug-resistant (MDR) bacteria and distinguish between pathogenic and beneficial microorganisms. Additionally, the engineered anti-CRISPR gene-containing phages in combination with antibiotics could be used as a cutting-edge treatment approach to reduce antibiotic resistance.
细菌中抗生素耐药性的出现和发展对全球公共卫生构成严重威胁。抗生素耐药基因（ARGs）通常位于移动遗传元件（MGEs）上。它们可通过水平基因转移（HGT）在细菌之间转移，导致耐药菌株的传播和抗生素治疗失败。CRISPR（成簇规律间隔短回文重复序列）-Cas（CRISPR相关基因）是细菌在长期选择压力下为限制HGT而发展出的众多策略之一。CRISPR-Cas系统存在于约一半的细菌基因组中，在限制抗生素耐药性传播方面发挥着重要作用。另一方面，噬菌体和其他MGEs编码多种抗CRISPR蛋白（Acrs）以对抗CRISPR-Cas系统的免疫作用。这些Acrs可降低CRISPR-Cas系统对噬菌体的活性，并促进细菌获得ARGs和毒力性状。本综述旨在评估CRISPR-Cas系统和Acrs与细菌抗生素耐药性之间的关系。我们还强调了利用CRISPR技术和Acrs来控制和预防细菌耐药性。CRISPR-Cas系统能够高精度、可靠地靶向核酸序列；因此，它已成为一种新型的基因编辑和基因治疗工具，用于防止抗生素耐药性的传播。基于CRISPR的方法可能为开发智能抗生素铺平道路，这种智能抗生素可以消灭多重耐药（MDR）细菌，并区分致病微生物和有益微生物。此外，经过工程改造的含抗CRISPR基因的噬菌体与抗生素联合使用，可作为一种前沿治疗方法来降低抗生素耐药性。
