Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Ann N Y Acad Sci. 2023 Jun;1524(1):51-64. doi: 10.1111/nyas.14991. Epub 2023 Apr 2.
Antimicrobial resistance is at an all-time high and new drugs are required to overcome this crisis. Traditional approaches to drug discovery have failed to produce novel classes of antibiotics, with only a few currently in development. It is thought that novel classes will come from antibacterial drug discovery efforts that focus on unconventional targets. One such collection of antibacterial targets are those that comprise central carbon metabolism. Targets of this kind have been largely overlooked because conventional antibacterial testing media are ill-suited for exploring carbon source utilization. Nevertheless, as a consequence of infection, bacteria must find a carbon source in order to survive. Here, we review what is known about the carbon sources available and used by bacteria in different host infection sites. We also look at discovery efforts targeting central carbon metabolism and evaluate how these processes can influence antibiotic efficacy.
抗菌药物耐药性处于历史最高水平，需要新的药物来克服这一危机。传统的药物发现方法未能产生新的抗生素类别，目前只有少数几种正在开发中。人们认为，新型抗生素将来自于专注于非传统靶点的抗菌药物发现努力。其中一类抗菌靶点是构成中心碳代谢的靶点。这类靶点在很大程度上被忽视了，因为传统的抗菌测试介质不适合探索碳源利用。然而，由于感染，细菌必须找到碳源才能生存。在这里，我们回顾了在不同宿主感染部位细菌可用和使用的碳源。我们还研究了针对中心碳代谢的发现工作，并评估了这些过程如何影响抗生素的疗效。
