Bromoenterobactins as Potent Inhibitors of a Pathogen-Associated, Siderophore-Modifying C-Glycosyltransferase

IroB is a C-glycosyltransferase encoded in the iroA cluster. 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 bo...

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Veröffentlicht in:Journal of the American Chemical Society 2006-07, Vol.128 (29), p.9324-9325
Hauptverfasser: Lin, Hening, Fischbach, Michael A, Gatto, Gregory J, Liu, David R, Walsh, Christopher T
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Sprache:eng
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Zusammenfassung:IroB is a C-glycosyltransferase encoded in the iroA cluster. 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 against iroA-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 targeting iroA-containing bacteria.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja063236x