Choudhary M Iqbal, Römling Ute, Nadeem Faiza, Bilal Hafiz Muhammad, Zafar Munirah, Jahan Humera, Ur-Rahman Atta
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Microorganisms. 2022 Dec 21;11(1):16. doi: 10.3390/microorganisms11010016.
Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.
抗菌耐药性和耐受性是微生物因对各种异源生物制剂进行进化适应而产生的自然现象。这些适应机制使得当前的治疗选择面临挑战，因为治疗广泛的感染、相关生物膜形成、细胞内和宿主适应性微生物以及持续存在的细胞和处于受保护生态位中的微生物变得越来越困难。因此，需要新的策略来确定最有前景的药物靶点，以克服传染病治疗中现有的障碍。此外，由于在过去二十年中几乎没有引入新的抗菌药物，因此也非常需要发现新的候选药物。在这篇综述中，我们重点关注可能有助于开发能够干扰微生物耐药机制的创新小分子的策略。我们还强调了在优化模拟宿主条件的生长培养基以及对抗菌剂的微生物反应进行基因组规模分子分析方面的最新进展。此外，我们根据生物膜细胞独特的生理学和代谢来讨论抗生物膜分子的鉴定及其作用机制。因此，本综述提供了在模拟宿主生长培养基以有效发现和开发抗菌及抗生物膜药物方面的最新进展。
