de la Fuente Tagarro Carlos, Martín-González Diego, De Lucas Andrea, Bordel Sergio, Santos-Beneit Fernando
Department of Chemical Engineering and Environmental Technology, School of Industrial Engineering, University of Valladolid, Paseo Prado de la Magdalena 3-5, 47011 Valladolid, Spain.
Institute of Sustainable Processes, Paseo Prado de la Magdalena 3-5, 47011 Valladolid, Spain.
Antibiotics (Basel). 2024 Nov 27;13(12):1141. doi: 10.3390/antibiotics13121141.
CRISPR/Cas systems have emerged as valuable tools to approach the problem of antimicrobial resistance by either sensitizing or lysing resistant bacteria or by aiding in antibiotic development, with successful applications across diverse organisms, including bacteria and fungi. CRISPR/Cas systems can target plasmids or the bacterial chromosome of AMR-bacteria, and it is especially necessary to have an efficient entry into the target cells, which can be achieved through nanoparticles or bacteriophages. Regarding antibiotic development and production, though the use of CRISPR/Cas in this field is still modest, there is an untapped reservoir of bacterial and fungal natural products, with over 95% yet to be characterized. In , a key antibiotic-producing bacterial genus, CRISPR/Cas has been successfully used to activate silent biosynthetic gene clusters, leading to the discovery of new antibiotics. CRISPR/Cas is also applicable to non-model bacteria and different species of fungi, making it a versatile tool for natural products discovery. Moreover, CRISPR/Cas-based studies offer insights into metabolic regulation and biosynthetic pathways in both bacteria and fungi, highlighting its utility in understanding genetic regulation and improving industrial strains. In this work, we review ongoing innovations on ways to treat antimicrobial resistances and on antibiotic discovery using CRISPR/Cas platforms, highlighting the role of bacteria and fungi in these processes.
CRISPR/Cas系统已成为解决抗菌耐药性问题的重要工具，可通过使耐药细菌敏感或裂解，或辅助抗生素研发来实现，已在包括细菌和真菌在内的多种生物体中成功应用。CRISPR/Cas系统可靶向抗微生物耐药性细菌的质粒或细菌染色体，尤其需要高效进入靶细胞，这可通过纳米颗粒或噬菌体来实现。关于抗生素的研发和生产，尽管CRISPR/Cas在该领域的应用仍较少，但细菌和真菌天然产物有尚未开发的宝库，超过95%的产物尚未被表征。在关键的抗生素生产细菌属中，CRISPR/Cas已成功用于激活沉默的生物合成基因簇，从而发现新的抗生素。CRISPR/Cas也适用于非模式细菌和不同种类的真菌，使其成为发现天然产物的通用工具。此外，基于CRISPR/Cas的研究为细菌和真菌的代谢调控及生物合成途径提供了见解，凸显了其在理解基因调控和改良工业菌株方面的效用。在本研究中，我们综述了利用CRISPR/Cas平台治疗抗菌耐药性和发现抗生素的创新进展，强调了细菌和真菌在这些过程中的作用。
