Microcin E492, A Channel-Forming Bacteriocin from Klebsiella pneumoniae, Induces Apoptosis in Some Human Cell Lines

The cytotoxic effect of microcin E492, a low-molecular-mass channel-forming bacteriocin (7,887 Da) produced by a strain of Klebsiella pneumoniae, was characterized in HeLa cells. At low (5 µg/ml) and intermediate (10 µg/ml) concentrations, microcin E492 induced biochemical and morphological changes...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (5), p.2696-2701
Main Authors: Hetz, Claudio, Bono, Maria Rosa, Barros, Luis Felipe, Lagos, Rosalba
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Apoptosis
B lymphocytes
Bacteria
Bacteriocins
Bacteriocins - pharmacology
Biochemistry
Biological Sciences
Calcium - metabolism
Caspases - metabolism
Cell Line
Cell lines
Cells
Cytochrome c Group - metabolism
Cytotoxins - pharmacology
DNA
Endothelial cells
Enzyme Activation
HeLa Cells
Humans
Intracellular Membranes - drug effects
Jurkat Cells
Klebsiella pneumoniae
membrane potential
Membrane Potentials - drug effects
microcin E492
Mitochondria - drug effects
Necrosis
Proteins
T lymphocytes
Tumor Cells, Cultured
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Summary:The cytotoxic effect of microcin E492, a low-molecular-mass channel-forming bacteriocin (7,887 Da) produced by a strain of Klebsiella pneumoniae, was characterized in HeLa cells. At low (5 µg/ml) and intermediate (10 µg/ml) concentrations, microcin E492 induced biochemical and morphological changes typical of apoptosis, such as cell shrinkage, DNA fragmentation, extracellular exposure of phosphatidylserine, caspase activation, and loss of mitochondrial membrane potential. Treatment with zVAD-fmk, a general caspase inhibitor, completely blocked the cytotoxic effect of this bacteriocin. At higher microcin concentrations (>20 µg/ml) a necrotic phenotype was observed. Induction of apoptosis by microcin E492 was associated with the release of calcium from intracellular stores, probably after microcin-triggered ion channel formation. Microcin E492 also presented a cytotoxic effect on Jurkat and RJ2.25 cells, but had no effect on KG-1 cells nor on a primary culture of human tonsil endothelial cells, suggesting that there is a specific interaction of the bacteriocin with components of the target cell surface. This report describes a bacteriocin that has the capacity to induce apoptosis in human cell lines.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.052709699