Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity.
Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity.
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DOI：
10.1016/j.mib.2021.03.007
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发表时间：
2021-06
影响因子：
5.4
通讯作者：
Carlson EE
中科院分区：
文献类型：
--
作者：
Fihn CA;Carlson EE
随着抗生素耐药性的上升和缺乏有效的策略来应对这一威胁，开发新的治疗方法至关重要。通过细菌的双组分系统（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）和同源反应调节因子（RR）组成，其中细菌可以具有多达160种不同的蛋白质。TCS通常不是生命所必需的，但控制许多毒力和抗药性机制。这一点，沿着它们在动物中的缺失使得TCS成为抗微生物治疗的有吸引力的靶标，无论是作为独立治疗还是作为现有治疗的佐剂。本文综述了针对HK ATP结合结构域的抑制剂的研究进展。由于该结构域是高度保守的，因此在单个生物体中破坏多个TCS以增加有效性并降低抗性进化的压力可能是可行的。
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 comprised 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.
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影响因子：
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