Abstract
Polymyxin B and colistin were examined for their ability to inhibit the type II NADH-quinone oxidoreductases (NDH-2) of three species of Gram-negative bacteria. Polymyxin B and colistin inhibited the NDH-2 activity in preparations from all of the isolates in a concentration-dependent manner. The mechanism of NDH-2 inhibition by polymyxin B was investigated in detail with Escherichia coli inner membrane preparations and conformed to a mixed inhibition model with respect to ubiquinone-1 and a non-competitive inhibition model with respect to NADH. These suggest that the inhibition of vital respiratory enzymes in the bacterial inner membrane represents one of the secondary modes of action for polymyxins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acinetobacter baumannii / drug effects
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Acinetobacter baumannii / enzymology
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Anti-Bacterial Agents / pharmacology
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Cell Membrane / drug effects
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Cell Membrane / enzymology
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Colistin / analogs & derivatives
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Colistin / pharmacology*
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Gram-Negative Bacteria / drug effects*
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Gram-Negative Bacteria / enzymology*
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Klebsiella pneumoniae / drug effects
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Klebsiella pneumoniae / enzymology
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NAD / antagonists & inhibitors
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Polymyxin B / pharmacology*
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Quinone Reductases / antagonists & inhibitors*
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Quinone Reductases / drug effects
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Ubiquinone / antagonists & inhibitors
Substances
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Anti-Bacterial Agents
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NAD
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Ubiquinone
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colistinmethanesulfonic acid
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NADH dehydrogenase (quinone)
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Quinone Reductases
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Polymyxin B
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Colistin