Structural and functional diversity of microcins, gene-encoded antibacterial peptides from enterobacteria.
Microcins are a peculiar class of gene-encoded low-molecular-mass antibacterial peptides secreted by enterobacteria. They contribute to the regulation of microbial competitions within the intestinal microbiota. The genetic systems involved in microcin biosynthesis share a conserved organization. Similar to bacteriocins of Gram-positive bacteria, microcins exert potent antibacterial activity directed against phylogenetically-related bacterial strains, with minimal inhibitory concentrations in the nanomolar range. In contrast to bacteriocins, they display a great structural diversity among the few representatives well characterized until now, that makes difficult the description of microcin subclasses. This review focuses on three microcins, MccE492m that carries a C-terminal posttranslational modification containing a catechol-type siderophore, MccJ25, a cyclic peptide with a unique 'lasso-type' structure and MccC7 or C51, with a common N-formylated heptapeptide-nucleotide structure. We show these microcins exhibit 'Trojan horse' mechanisms of antibacterial activity: either (i) the microcin structure is a mime of an essential element, permitting its recognition by outer membrane receptors used for vital functions in bacteria and further translocation into the periplasmic space, or (ii) it is secreted as a harmless molecule and further processed in susceptible bacteria to form the toxic entity. When inside target bacteria, microcins bind essential enzymes or interact with the inner membrane to form a bacterial killing structure.
Duquesne
Sophie
S
Chemistry and Biochemistry of Natural Substances, UMR 5154 CNRS-National Museum of Natural History, Department Regulations, Development and Molecular Diversity, Paris, France.
Petit
Vanessa
V
Peduzzi
Jean
J
Rebuffat
Sylvie
S
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001430:Bacteriocins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D005798:Genes, Bacterial; D006094:Gram-Positive Bacteria / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D011487:Protein Conformation