Mycobacterium Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, India.
Division of Infectious Disease, Department of Medicine, & the Ruy V. Lourenço Centre for the Study of Emerging & Re-emerging Pathogens, Rutgers University - New Jersey Medical School, Newark, NJ 07107, USA.
Future Med Chem. 2020 Feb;12(4):339-355. doi: 10.4155/fmc-2019-0267. Epub 2020 Feb 7.
Infectious diseases continue to be a major cause of human mortality. With the emergence of drug resistance, diseases that were long thought to have been curable by antibiotics are resurging. There is an urgent clinical need for newer antibiotics that target novel cellular pathways to overcome resistance to currently used therapeutics. The base excision repair (BER) pathways of the pathogen restore altered bases and safeguard the genomic integrity of the pathogen from the host's immune response. Although the BER machinery is of paramount importance to the survival of the pathogens, its potential as a drug target is largely unexplored. In this review, we discuss the importance of BER in different pathogenic organisms and the potential of its inhibition with small molecules.
传染病仍然是人类死亡的主要原因。随着耐药性的出现,曾经被认为可以用抗生素治愈的疾病又卷土重来。目前迫切需要针对新型细胞途径的新型抗生素来克服对现有治疗方法的耐药性。病原体的碱基切除修复(BER)途径修复改变的碱基,并保护病原体的基因组完整性免受宿主免疫反应的影响。尽管 BER 机制对病原体的生存至关重要,但它作为药物靶点的潜力在很大程度上尚未得到探索。在这篇综述中,我们讨论了 BER 在不同病原体中的重要性以及用小分子抑制它的潜力。