With the rise in antimicrobial resistance and the dearth of effective strategies to combat this threat, the development of novel therapies is of utmost importance. Targeting of bacterial signaling through their the two-component systems (TCSs) may be a viable strategy. TCSs are comprisesd of a sensory histidine kinase (HK), of which a bacterium can have up to 160 distinct proteins, and a cognate response regulator (RR). The TCSs are generally non-essential for life, but control many virulence and antibiotic-resistance mechanisms. This, along with their absence in animals makes the TCSs an attractive target for antimicrobial therapy, whether as a stand-alone treatments or adjuvants for existing therapies. This review focuses on progress in the development of inhibitors that target the HK ATP-binding domain. Because this domain is highly conserved, it may be feasible to disrupt multiple TCSs within a single organism to increase effectiveness and reduce pressure for the evolution of resistance.

随着抗菌素耐药性的上升以及缺乏有效策略来应对这一威胁，开发新疗法至关重要。通过双组分系统（TCS）靶向细菌信号传导可能是一种可行的策略。 TCS 由感觉组氨酸激酶 (HK) 和同源反应调节剂 (RR) 组成，其中细菌最多可含有 160 种不同的蛋白质。 TCS 通常不是生命所必需的，但控制着许多毒力和抗生素耐药机制。这一点，加上它们在动物体内的缺失，使得 TCS 成为抗菌治疗的有吸引力的目标，无论是作为独立治疗还是现有治疗的佐剂。本综述重点关注针对 HK ATP 结合域的抑制剂的开发进展。由于该结构域高度保守，因此破坏单个生物体内的多个 TCS 以提高有效性并减少耐药性进化的压力可能是可行的。