Antibacterial and antitumorigenic properties of microcin E492, a pore-forming bacteriocin.
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.
Lagos
R
R
Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile. rolagos@uchile.cl
Tello
M
M
Mercado
G
G
García
V
V
Monasterio
O
O
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D001430:Bacteriocins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018272:Porins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001430:Bacteriocins; D018272:Porins; C020411:microcin