Antibacterial and Antitumorigenic Properties of Microcin E492, a Pore- Forming Bacteriocin

Author(s): R. Lagos, M. Tello, G. Mercado, V. Garcia, O. Monasterio

Journal Name: Current Pharmaceutical Biotechnology

Volume 10 , Issue 1 , 2009

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Microcins are a family of low-molecular weight bacteriocins produced and secreted by Gram-negative bacteria. This review is focused on microcin E492, a pore-forming bacteriocin produced by Klebsiella pneumoniae RYC492 that exerts its antibacterial action on related strains. The steps necessary for the production of active microcin E492 involve post-translational modification with a catechol-type siderophore at the C-terminal and proteolytic processing during export to the extracellular space. This bacteriocin has a modular structure, with a toxic domain at the N-terminal and an uptake domain at the C-terminal of the mature protein. The mechanism by which the C-terminal of microcin E492 is recognized by catecholate siderophore receptors is called the “Trojan horse” strategy, because the C-terminal structure mimics essential bacterial elements, which are recognized by the respective receptors and translocated across the outer membrane to exert antibacterial action. The C-terminal uptake module can be exchanged and used with other toxic domains. Microcin E492 also has a cytotoxic effect on malignant human cell lines. The cytotoxic mechanism is through apoptosis, a desired mechanism for cancer therapy. The ability of microcin E492 to form amyloid-like fibrils constitutes a property that can be exploited in the formulation of this bacteriocin as an antitumoral agent, because these fibrils can behave as stable depots to ensure the sustained release of a biologically active molecule. Alternatively, live bacteria can be used as a continuous source of microcin E492 production in specific tumors.

Keywords: Microcin E492, channel-forming bacteriocin, antitumoral bacteriocin, amyloid-like fibrils, salmochelin, siderophore- peptide, cancer therapy

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Article Details

Year: 2009
Page: [74 - 85]
Pages: 12
DOI: 10.2174/138920109787048643

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