Bromoenterobactins as potent inhibitors of a pathogen-associated, siderophore-modifying C-glycosyltransferase.
Bromoenterobactins as potent inhibitors of a pathogen-associated, siderophore-modifying C-glycosyltransferase.
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溴肠杆菌素是病原体相关铁载体修饰 C-糖基转移酶的有效抑制剂。
DOI：
10.1021/ja063236x
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发表时间：
2006
影响因子：
15
通讯作者：
Walsh,ChristopherT
中科院分区：
文献类型：
--
作者：
Lin,Hening;Fischbach,MichaelA;GattoJr,GregoryJ;Liu,DavidR;Walsh,ChristopherT
IroB是一种C-糖基转移酶，由IroA簇编码，IroB对细菌铁载体肠杆菌素的C-糖基化是某些病原菌逃避由脂质运载蛋白2（Lcn 2）介导的宿主先天免疫的策略。如果没有这种修饰，肠杆菌素可以与宿主Lcn 2紧密结合，使其作为铁载体无效。因此，IroB抑制剂可能成为抗携带IroA病原菌的潜在抗生素。我们使用肠杆菌素类似物来探测IroB的活性位点的性质，并发现在2，3-二羟基苯甲酰基环的C5位置溴化的肠杆菌素类似物是IroB的有效抑制剂。这一发现可能会导致发现有效的抗生素靶向含gingiroA的细菌。
IroB is aC-glycosyltransferase encoded in theiroAcluster.C-Glucosylation of the bacterial siderophore enterobactin by IroB is a strategy some pathogenic bacteria use to evade the host's innate immunity mediated by lipocalin 2 (Lcn2). Without this modification, enterobactin can be tightly bound by host Lcn2, rendering it ineffective as a siderophore. Therefore, IroB inhibitors could be potential antibiotics againstiroA-harboring pathogenic bacteria. We used enterobactin analogues to probe the properties of the active site of IroB and found that enterobactin analogues brominated at the C5 positions of the 2,3-dihydroxybenzoyl rings are potent inhibitors of IroB. This finding could lead to the discovery of effective antibiotics targetingiroA-containing bacteria.