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Structure and Function of Salmochelins and Microcins M/H47

Fachliche Zuordnung Stoffwechselphysiologie, Biochemie und Genetik der Mikroorganismen
Förderung Förderung von 2004 bis 2011
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5468788
 
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.
DFG-Verfahren Forschungsgruppen
 
 

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