title: Growth inhibition of pathogenic bacteria by sulfonylurea herbicides.
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.
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Kreisberg
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ong
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Krishna
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Joseph
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Catherine
authors.initials: C
authors.lastname: Ong
authors.forename: Hui Ann
authors.initials: HA
authors.lastname: Ooi
authors.forename: Julie C
authors.initials: JC
authors.lastname: Sung
authors.forename: Chern Chiang
authors.initials: CC
authors.lastname: Siew
authors.forename: Grace C
authors.initials: GC
authors.lastname: Chang
authors.forename: Fabrice
authors.initials: F
authors.lastname: Biot
authors.forename: Jon
authors.initials: J
authors.lastname: Cuccui
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Joey
authors.initials: J
authors.lastname: Chan
authors.forename: Suppiah P
authors.initials: SP
authors.lastname: Sivalingam
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D000597:Amino Acids, Branched-Chain / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D005260:Female; D006540:Herbicides / Q000494:pharmacology*; D008554:Melioidosis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D016019:Survival Analysis
chemical_list: D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; D006540:Herbicides; D013453:Sulfonylurea Compounds; D000095:Acetolactate Synthase