《自然》：抗生素的一个新的作用目标

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抗生素的一个新的作用目标

传统抗生素通过抑制重要病原体功能来发挥作用，它们因此也容易受病原体所形成的抗药性的影响。一种替代的办法是以支持病原体生长的宿主因子为作用靶点。现在，研究人员通过对能够抑制鼠伤寒沙门氏菌和结核分枝杆菌细胞内生长的激酶所进行的一项新颖的RNA干涉筛选，识别出这种方法的一个可能的作用靶点。这种关键分子是AKT1，它是一种激酶，以前被称为PKB，因其所具有的抗细胞程序死亡活性和在失控癌症中所起作用而被人们广泛研究。

Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1

With the emergence of multidrug resistant (MDR) bacteria, it is imperative to develop new intervention strategies. Current antibiotics typically target pathogen rather than host-specific biochemical pathways1. The researchers have developed kinase inhibitors that prevent intracellular growth of unrelated pathogens such as Salmonella typhimurium and Mycobacterium tuberculosis. An RNA interference screen of the human kinome using automated microscopy revealed several host kinases capable of inhibiting intracellular growth of S. typhimurium. The kinases identified clustered in one network around AKT1 (also known as PKB). Inhibitors of AKT1 prevent intracellular growth of various bacteria including MDR-M. tuberculosis. AKT1 is activated by the S. typhimurium effector SopB, which promotes intracellular survival by controlling actin dynamics through PAK4, and phagosome-lysosome fusion through the AS160 (also known as TBC1D4)-RAB14 pathway. AKT1 inhibitors counteract the bacterial manipulation of host signalling processes, thus controlling intracellular growth of bacteria.