Ndagi Umar, Falaki Abubakar A, Abdullahi Maryam, Lawal Monsurat M, Soliman Mahmoud E
Centre for Trans-Sahara Disease, Vaccine and Drug Research, Ibrahim Badamasi Babangida University Lapai Niger State Nigeria
Department of Microbiology, School of Agriculture and Applied Sciences, University of KwaZulu-Natal Durban 4001 South Africa.
RSC Adv. 2020 May 14;10(31):18451-18468. doi: 10.1039/d0ra01484b. eCollection 2020 May 10.
The use of antibiotics to manage infectious diseases dates back to ancient civilization, but the lack of a clear distinction between the therapeutic and toxic dose has been a major challenge. This precipitates the notion that antibiotic resistance was from time immemorial, principally because of a lack of adequate knowledge of therapeutic doses and continuous exposure of these bacteria to suboptimal plasma concentration of antibiotics. With the discovery of penicillin by Alexander Fleming in 1924, a milestone in bacterial infections' treatment was achieved. This forms the foundation for the modern era of antibiotic drugs. Antibiotics such as penicillins, cephalosporins, quinolones, tetracycline, macrolides, sulphonamides, aminoglycosides and glycopeptides are the mainstay in managing severe bacterial infections, but resistant strains of bacteria have emerged and hampered the progress of research in this field. Recently, new approaches to research involving bacteria resistance to antibiotics have appeared; these involve combining the molecular understanding of bacteria systems with the knowledge of bioinformatics. Consequently, many molecules have been developed to curb resistance associated with different bacterial infections. However, because of increased emphasis on the clinical relevance of antibiotics, the synergy between study and study is well cemented and this facilitates the discovery of potent antibiotics. In this review, we seek to give an overview of earlier reviews and molecular and structural understanding of bacteria resistance to antibiotics, while focusing on the recent bioinformatics approach to antibacterial drug discovery.
使用抗生素治疗传染病可追溯到古代文明,但治疗剂量和毒性剂量缺乏明确区分一直是一个重大挑战。这催生了抗生素耐药性自古就有的观念,主要是因为缺乏对治疗剂量的充分了解,以及这些细菌持续暴露于次优血浆浓度的抗生素中。1924年亚历山大·弗莱明发现青霉素,实现了细菌感染治疗的一个里程碑。这奠定了抗生素药物现代时代的基础。青霉素、头孢菌素、喹诺酮、四环素、大环内酯、磺胺类、氨基糖苷类和糖肽类等抗生素是治疗严重细菌感染的主要药物,但耐药菌株已经出现并阻碍了该领域的研究进展。最近,出现了涉及细菌对抗生素耐药性的新研究方法;这些方法将对细菌系统的分子理解与生物信息学知识相结合。因此,已经开发出许多分子来抑制与不同细菌感染相关的耐药性。然而,由于越来越强调抗生素的临床相关性,各项研究之间的协同作用得到了很好的巩固,这有助于发现有效的抗生素。在这篇综述中,我们试图概述早期的综述以及对细菌对抗生素耐药性的分子和结构理解,同时关注最近用于抗菌药物发现的生物信息学方法。