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

Curr Pharm Biotechnol. 2009 Jan;10(1):74-85. doi: 10.2174/138920109787048643.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Antineoplastic Agents / chemistry*
  • Bacteriocins / chemistry*
  • Bacteriocins / genetics
  • Bacteriocins / pharmacology
  • Bacteriocins / therapeutic use
  • Humans
  • Porins / chemistry*
  • Porins / genetics
  • Porins / physiology*

Substances

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