Growth inhibition of pathogenic bacteria by sulfonylurea herbicides

Antimicrob Agents Chemother. 2013 Mar;57(3):1513-7. doi: 10.1128/AAC.02327-12. Epub 2012 Dec 21.

Abstract

Emerging resistance to current antibiotics raises the need for new microbial drug targets. We show that targeting branched-chain amino acid (BCAA) biosynthesis using sulfonylurea herbicides, which inhibit the BCAA biosynthetic enzyme acetohydroxyacid synthase (AHAS), can exert bacteriostatic effects on several pathogenic bacteria, including Burkholderia pseudomallei, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our results suggest that targeting biosynthetic enzymes like AHAS, which are lacking in humans, could represent a promising antimicrobial drug strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetolactate Synthase / antagonists & inhibitors*
  • Acetolactate Synthase / metabolism
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / enzymology
  • Acinetobacter baumannii / growth & development
  • Amino Acids, Branched-Chain / antagonists & inhibitors
  • Amino Acids, Branched-Chain / biosynthesis
  • Animals
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Burkholderia pseudomallei / drug effects*
  • Burkholderia pseudomallei / enzymology
  • Burkholderia pseudomallei / growth & development
  • Female
  • Herbicides / pharmacology*
  • Melioidosis / drug therapy
  • Melioidosis / microbiology
  • Melioidosis / mortality
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / mortality
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / growth & development
  • Sulfonylurea Compounds / pharmacology*
  • Survival Analysis

Substances

  • Amino Acids, Branched-Chain
  • Bacterial Proteins
  • Herbicides
  • Sulfonylurea Compounds
  • Acetolactate Synthase