Antibacterial agents that inhibit two-component signal transduction systems
Antibacterial agents that inhibit two-component signal transduction systems
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DOI：
10.1073/pnas.95.9.5317
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发表时间：
1998-04-28
影响因子：
11.1
通讯作者：
Hoch, JA
中科院分区：
文献类型：
--
作者：
Barrett, JF;Goldschmidt, RM;Hoch, JA
已经发现了一类抑制革兰氏阳性致病菌生长的抗菌药物。RWJ-49815是疏水酪胺家族的代表，除了是有效的杀菌革兰氏阳性抗菌剂外，还在体外抑制KinA：：Spo 0 F双组分信号转导系统的激酶A的自磷酸化。RWJ-49815的类似物在其抑制细菌生长的能力方面变化很大，并且这种能力与其作为激酶A抑制剂的活性直接相关。与强效喹诺酮类药物环丙沙星相比，RWJ-49815在实验室传代实验中表现出较低的耐药性出现。抑制组氨酸蛋白激酶：：反应调节剂的两个组件的信号转导途径可能会提供一个机会，抑制染色体耐药的出现，在一个单一的细菌中的一个单一的抑制剂靶向多个蛋白质。这类抑制剂可能代表一类抗菌药物，可能代表抗菌治疗的突破。
A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Grampositive antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F two-component signal transduction system in vitro. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase::response regulator two component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.