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

Deris ZZ 1 , Akter J 2 , Sivanesan S 2 , Roberts KD 3 , Thompson PE 3 , Nation RL 2 Show all authors , Li J 2 , Velkov T 2

Affiliations 

  • 1 1] Department of Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia [2] Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
  • 2 Department of Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia
  • 3 Department of Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia
J Antibiot (Tokyo), 2014 Feb;67(2):147-51.
PMID: 24169795 DOI: 10.1038/ja.2013.111

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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