Antibacterial and antitumorigenic properties of microcin E492, a pore-forming bacteriocin.

Abstract

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.

• Authors: R Lagos, M Tello, G Mercado, V García, O Monasterio
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 10 Issue 1 Pg. 74-85 (Jan 2009) ISSN: 1873-4316 [Electronic] Netherlands
• PMID: 19149591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Bacterial Agents
• Antineoplastic Agents
• Bacteriocins
• Porins
• microcin

Topics

• Animals
• Anti-Bacterial Agents (chemistry)
• Antineoplastic Agents (chemistry)
• Bacteriocins (chemistry, genetics, pharmacology, therapeutic use)
• Humans
• Porins (chemistry, genetics, physiology)