Parasitism of iron-siderophore receptors of Escherichia coli by the siderophore-peptide microcin E492m and its unmodified counterpart.
Microcin E492 (MccE492) is an antibacterial peptide naturally secreted by Klebsiella pneumoniae RYC492. Initially described as an 84-residue unmodified peptide, it was also recently isolated in a posttranslationally modified form, MccE492m. The production of MccE492m is dependent on the synthesis of enterobactin and the mceABCDEFGHIJ gene cluster. The posttranslational modification was characterized as a trimer of N-(2,3-dihydroxybenzoyl)-L-serine (DHBS) linked to the Ser84-carboxylate via a beta-D-glucose moiety. MccE492m was shown to bind ferric ions through the trimer of DHBS. This is the first example of a novel type of antibacterial peptide termed siderophore-peptide. Recognition of MccE492m, but also of the unmodified MccE492, was shown to be mediated by the catecholate siderophore receptors FepA, Cir and Fiu at the outer membrane of E. coli. The siderophore-type modification was shown to be responsible for a significant enhancement of the microcin antibacterial activity. Therefore, we propose that MccE492 and MccE492m use iron-siderophore receptors for uptake into the target bacteria and that improvement of MccE492 antimicrobial activity upon modification results from an increase in the microcin/receptor affinity.
Destoumieux-Garzón
Delphine
D
Chemistry, Biochemistry of Natural Substances, Department Regulations, Development and Molecular Diversity, UMR 5154 CNRS--National Museum of Natural History, 63 rue Buffon, 75005, Paris, France.
Peduzzi
Jean
J
Thomas
Xavier
X
Djediat
Chakib
C
Rebuffat
Sylvie
S
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D004755:Enterobacteriaceae / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001430:Bacteriocins; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; C035902:siderophore receptors; C020411:microcin; D007501:Iron