A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity

Zakuan Zainy Deris, Jesmin Akter, Sivashangarie Sivanesan, Kade Douglas Roberts, Philip Thompson, Roger Leigh Nation, Jian Li, Tony Velkov

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76 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)147 - 151
Number of pages5
JournalJournal of Antibiotics
Volume67
Issue number2
DOIs
Publication statusPublished - 2014

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