Structural and Functional Diversity of Microcins, Gene-Encoded Antibacterial Peptides from Enterobacteria

Abstract

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.

Small Toxic Proteins and the Antisense RNAs That Repress Them

“…TisB has also recently been found to fractionate with the inner membrane (52). It is tempting to speculate that the type I toxin proteins might act extracellularly, similar to toxic microcin peptides (10). However, there are no data to support this hypothesis, and exogenously applied Hok did not significantly kill the six bacterial strains tested, including E. coli (43).…”

Mechanisms of maintenance of intestinal homeostasis by autochthonic microbiota and probiotics

“…Bakteriocyny zwiększają przepuszczalność ściany komórkowej bakterii Gram-ujemnych, interferują z syntezą ściany komórkowej i wiążąc się z prekursorem peptydoglikanu, tworzą w niej pory. Mikrocyny łączą się z warstwą wewnętrzną ściany komórkowej i enzymami uczestniczącymi w syntezie DNA, RNA i białek (10,27). Znanymi producentami mikrocyn jest wiele szczepów różnych gatunków Lactobacillus hamujących wzrost między innymi pałeczek Listeria monocytogenes, ziarniaków Enterococcus spp.…”

Antimicrobial Peptides: New Frontiers in the Therapy of Infections

“…Whereas many antimicrobial peptides of bacterial origin are produced by large multidomain enzyme complexes termed peptide synthetases, microcins are typically produced as ribosomally synthesized precursors, similar to the bacteriocins from Gram-positive bacteria. Microcins are encoded by plasmid-or chromosome-located gene clusters, which typically include open reading frames encoding the microcin precursor, self-immunity factors, secretion proteins and modification enzymes, g i v i n g r i s e t o a n a m a z i n g d i v e r s i t y o f microcin structures and mechanisms of action (Duquesne et al, 2007). Microcins are secreted by enterobacteria (mostly E. coli) under conditions of nutrient depletion, and are involved in the regulation of microbial competition within the intestinal microbiota.…”

“…They are generally hydrophobic, highly resistant to heat, extreme pH and proteases, and exert potent antibacterial activity in nanomolar concentrations, usually against a narrow spectrum of closely related species. Their mechanism of action has been defined as a "Trojan horse" behavior: they are recognized as siderophores by the outer membrane receptors of susceptible bacteria, and as such internalized; once inside they bind essential enzymes or interact with the inner membrane killing the bacterium (Duquesne et al, 2007). At present microcins are still into the characterization phase, and despite their potent antibacterial activity, they are not being developed as antibacterials (Corsini et al, 2010).…”