Structure and Function of Salmochelins and Microcins M/H47

对于许多致病细菌，铁供应是一个关键因素，因为在它们的宿主中，铁与蛋白质结合。在低铁生长条件下E.大肠杆菌分泌一种铁载体（铁络合剂），称为肠杆菌素（肠螯合素）。特异性高亲和力转运系统允许铁肠杆菌素的摄取，以提供生长所需的铁。自1970年以来，人们一直认为肠杆菌素是沙门氏菌菌株的主要铁载体。然而，我们最近发现，salmochelin，二葡萄糖基化肠杆菌素是主要的铁载体分泌的大多数沙门氏菌菌株。螯鲑素的合成和利用由iroBCDEN基因编码。在计划中的项目中，将对新型螯鲑素及其降解产物的化学结构进行表征。此外，还将用化学和遗传学方法研究和表征基因产物在生物合成、运输和降解中的功能和活性。由于肠杆菌素在哺乳动物中被血清白蛋白强烈结合，在炎症中被NGAL脂质运载蛋白强烈结合，因此宿主的这些先天防御机制似乎使肠杆菌素成为病原菌的劣质铁载体。因此，将检查螯鲑素与白蛋白和NGAL脂质运载蛋白的结合特性。第二部分研究了几株产沙门氏菌螯铁蛋白的大肠杆菌分泌的微菌素H47和M。大肠杆菌菌株。这些微菌素能杀死广谱的不同的大肠杆菌。大肠杆菌菌株，并使用与salmochelins和肠杆菌素相同的儿茶酚盐铁载体受体。此外，基因mcmL和mcmK是iroB和iroD的同源物，在微球蛋白H47和M生物合成的基因簇中被发现。通过对这些微菌素的结构鉴定，可以对McmL和McmK的可能修饰作用以及微菌素的功能进行初步的探讨。

For many pathogenic bacteria iron supply is a critical factor since in their host iron is bound to proteins. Under low iron growth conditions E. coli secretes a siderophore (iron complexing agent) called enterobactin (enterochelin). Specific high affinity transport systems allow the uptake of iron-enterobactin in order to supply the iron necessary for growth. Since 1970 it has been assumed that enterobactin is a major siderophore of Salmonella strains. However, we recently showed that salmochelin, a diglucosylated enterobactin is the principal siderophore secreted by most Salmonella strains. Synthesis and utilization of salmochelin is encoded by the iroBCDEN genes. In the planned project, the chemical structures of novel salmochelins and its degradation products will be characterized. Furthermore, the functions and activities of the gene products in biosynthesis, transport and degradation will be studied and characterized with chemical and genetic methods. Since, enterobactin is avidly bound in the mammal by serum albumins and in inflammation by NGAL lipocalin, these innate defense mechanisms of the host seem to make enterobactin an inferior siderophore for pathogenic bacteria. Therefore, the binding properties of salmochelins to albumins and NGAL lipocalin will be examined. The second part of the project is focused on microcins H47 and M secreted by several salmochelin producing E. coli strains. These microcins kill a broad spectrum of different E. coli strains and use the same catecholate siderophore receptors as salmochelins and enterobactin. Furthermore, the genes mcmL and mcmK, which are homologs of iroB and iroD, are found in the gene cluster for microcin H47 and M biosynthesis. With the structure elucidation of these microcins conclusions are expected on the putative modification by McmL and McmK and on the function of microcins.