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

被引:73
作者
Lagos, R. [1 ]
Tello, M. [1 ]
Mercado, G. [1 ]
Garcia, V. [1 ]
Monasterio, O. [1 ]
机构
[1] Univ Chile, Fac Ciencias, Dept Biol, Santiago, Chile
关键词
Microcin E492; channel-forming bacteriocin; antitumoral bacteriocin; amyloid-like fibrils; salmochelin; siderophore-peptide; cancer therapy; ESCHERICHIA-COLI STRAINS; GRAM-NEGATIVE BACTERIA; IN-VITRO CHARACTERIZATION; IROA GENE-CLUSTER; HUMAN CELL-LINES; KLEBSIELLA-PNEUMONIAE; ABC TRANSPORTERS; SIDEROPHORE-PEPTIDE; OUTER-MEMBRANE; POSTTRANSLATIONAL MODIFICATION;
D O I
10.2174/138920109787048643
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:74 / 85
页数:12
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