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Microcin

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Background

Bacterial drug resistance is a very important medical problem, and identifying new antimicrobial agents and new drug targets is an important goal. Microcins are peptides synthesized by ribosomes and, in some cases, are post-translationally modified. Microcins are a peculiar class of gene-encoded low-molecular-mass antibacterial peptides secreted by enterobacteria and active against closely related bacterial species. They help regulate microbial competition within the gut microbiota. They are essentially hydrophobic and form a very restricted, but highly heterogeneous, class of bacteriocins, with 14 representatives identified to date, among which only eight have been isolated and structurally characterized. Microcins are classified into two groups based on their molecular mass and the presence or absence of disulfide bonds and post-translational modifications. Microcins are encoded by genetic systems with conserved tissues. They are precursor peptides consisting of an N-terminal leader peptide extension and a core peptide.

The Functions of Microcins

Microcins have been discovered as molecules influencing interbacterial interactions in complex microbial ecosystems, regulating microbial communities. Microcins might have functions involving interactions with eukaryotic host cells. An important aspect is whether microcins can cross the gut-blood barrier to have systemic effects on the host. Microcins and their related molecules may also have regulatory functions in bacterial cells. Microcins may function to maintain bacterial mobile genetic elements such as plasmids; so as a post-segregational killing mechanism; in other words, bacteria that lose their plasmids are punished by cell death. The efficiency of microcins depends on their secretion in the environment, where they accumulate and reach concentrations necessary to inhibit the growth of bacterial competitors.

Mechanisms of Action

Microcins are antibiotic peptides that block important functions of target cells. They act by forming pores in the bacterial membrane, inhibiting aspartyl-tRNA synthetase, essential in protein synthesis (MccC), inhibiting the DNA gyrase GyrB, resulting in double DNA breaks. Some others block the secondary RNA polymerase channel, impairing transcription and acting on cytochromes to inhibit cellular respiration, impairing the cellular proton channel, or the ATP synthase.

Mechanisms of action of Trojan horse microcins.Fig.1 Mechanisms of action of Trojan horse microcins. (Rebuffat, 2012)

Advantages

Microcins exert their potent and selective antimicrobial activities through original, sometimes unique, mechanisms that can be excellent models for scientists to generate potent and selective drugs by mimicking these elegant and sophisticated strategies.

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Reference:

  1. Rebuffat, S. Microcins in action: amazing defence strategies of Enterobacteria. Biochemical Society Transactions. 2012, 40(6): 1456-1462.
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