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

Research output: Contribution to journalArticleResearchpeer-review

54 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

Cite this

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title = "A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity",
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.",
author = "Deris, {Zakuan Zainy} and Jesmin Akter and Sivashangarie Sivanesan and Roberts, {Kade Douglas} and Philip Thompson and Nation, {Roger Leigh} and Jian Li and Tony Velkov",
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pages = "147 -- 151",
journal = "Journal of Antibiotics",
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A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity. / Deris, Zakuan Zainy; Akter, Jesmin; Sivanesan, Sivashangarie; Roberts, Kade Douglas; Thompson, Philip; Nation, Roger Leigh; Li, Jian; Velkov, Tony.

In: Journal of Antibiotics, Vol. 67, No. 2, 2014, p. 147 - 151.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity

AU - Deris, Zakuan Zainy

AU - Akter, Jesmin

AU - Sivanesan, Sivashangarie

AU - Roberts, Kade Douglas

AU - Thompson, Philip

AU - Nation, Roger Leigh

AU - Li, Jian

AU - Velkov, Tony

PY - 2014

Y1 - 2014

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AB - 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.

UR - http://www.nature.com/ja/journal/v67/n2/full/ja2013111a.html

U2 - 10.1038/ja.2013.111

DO - 10.1038/ja.2013.111

M3 - Article

VL - 67

SP - 147

EP - 151

JO - Journal of Antibiotics

JF - Journal of Antibiotics

SN - 0021-8820

IS - 2

ER -