Hirakawa Hidetada, Kurushima Jun, Hashimoto Yusuke, Tomita Haruyoshi
Department of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi Gunma 371-8511, Japan.
Laboratory of Bacterial Drug Resistance, Graduate School of Medicine, Gunma University, Maebashi Gunma 371-8511, Japan.
Antibiotics (Basel). 2020 Sep 23;9(10):635. doi: 10.3390/antibiotics9100635.
Bacteria adapt to changes in their environment using a mechanism known as the two-component regulatory system (TCS) (also called "two-component signal transduction system" or "two-component system"). It comprises a pair of at least two proteins, namely the sensor kinase and the response regulator. The former senses external stimuli while the latter alters the expression profile of bacterial genes for survival and adaptation. Although the first TCS was discovered and characterized in a non-pathogenic laboratory strain of , it has been recognized that all bacteria, including pathogens, use this mechanism. Some TCSs are essential for cell growth and fitness, while others are associated with the induction of virulence and drug resistance/tolerance. Therefore, the TCS is proposed as a potential target for antimicrobial chemotherapy. This concept is based on the inhibition of bacterial growth with the substances acting like conventional antibiotics in some cases. Alternatively, TCS targeting may reduce the burden of bacterial virulence and drug resistance/tolerance, without causing cell death. Therefore, this approach may aid in the development of antimicrobial therapeutic strategies for refractory infections caused by multi-drug resistant (MDR) pathogens. Herein, we review the progress of TCS inhibitors based on natural and synthetic compounds.
细菌利用一种称为双组分调节系统（TCS）（也称为“双组分信号转导系统”或“双组分系统”）的机制来适应其环境变化。它由一对至少两种蛋白质组成，即传感激酶和应答调节因子。前者感知外部刺激，而后者改变细菌基因的表达谱以实现生存和适应。尽管第一个TCS是在一种非致病性实验室菌株中发现和表征的，但人们已经认识到所有细菌，包括病原体，都使用这种机制。一些TCS对细胞生长和适应性至关重要，而另一些则与毒力诱导和耐药性/耐受性有关。因此，TCS被提议作为抗微生物化疗的潜在靶点。这一概念基于在某些情况下用类似传统抗生素的物质抑制细菌生长。或者，靶向TCS可能减轻细菌毒力和耐药性/耐受性的负担，而不会导致细胞死亡。因此，这种方法可能有助于开发针对由多重耐药（MDR）病原体引起的难治性感染的抗微生物治疗策略。在此，我们综述基于天然和合成化合物的TCS抑制剂的研究进展。
