Enzymatic tailoring of enterobactin alters membrane partitioning and iron acquisition.
Enterobactin (Ent), a prototypic bacterial siderophore, is modified by both the C-glucosyltransferase IroB and the macrolactone hydrolase IroE in pathogenic bacteria that contain the iroA cluster. To investigate the possible effects of glucosylation and macrolactone hydrolysis on the physical properties of Ent, the membrane affinities and iron acquisition rates of Ent and Ent-derived siderophores were measured. The data obtained indicate that Ent has a high membrane affinity (K(x) = 1.5 x 10(4)) similar to that of ferric acinetoferrin, an amphiphile containing two eight-carbon hydrophobic chains. Glucosylation and macrolactone hydrolysis decrease the membrane affinity of Ent by 5-25-fold. Furthermore, in the presence of phospholipid vesicles, the iron acquisition rate is significantly increased by glucosylation and macrolactone hydrolysis, due to the resultant decrease in membrane sequestration of the siderophore. These results suggest that IroB and IroE enhance the ability of Ent-producing pathogens to acquire iron in membrane-rich microenvironments.
Luo
Minkui
M
Lin
Hening
H
Fischbach
Michael A
MA
Liu
David R
DR
Walsh
Christopher T
CT
Groves
John T
JT
D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004758:Enterobactin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D017262:Siderophores / Q000378:metabolism
D001426:Bacterial Proteins; D017262:Siderophores; D004758:Enterobactin; D007501:Iron