Triclosan is a broad-spectrum antibacterial agent that inhibits bacterial fatty acid synthesis at the enoyl-acyl carrier protein reductase (FabI) step. Resistance to triclosan in Escherichia coli is acquired through a missense mutation in the fabI gene that leads to the expression of FabI[G93V]. The specific activity and substrate affinities of FabI[G93V] are similar to FabI. Two different binding assays establish that triclosan dramatically increases the affinity of FabI for NAD+. In contrast, triclosan does not increase the binding of NAD+ to FabI[G93V]. The x-ray crystal structure of the FabI-NAD+-triclosan complex confirms that hydrogen bonds and hydrophobic interactions between triclosan and both the protein and the NAD+ cofactor contribute to the formation of a stable ternary complex, with the drug binding at the enoyl substrate site. These data show that the formation of a noncovalent "bi-substrate" complex accounts for the effectiveness of triclosan as a FabI inhibitor and illustrates that mutations in the FabI active site that interfere with the formation of a stable FabI-NAD+-triclosan ternary complex acquire resistance to the drug.
Antimicrobial spectrum of triclosan, a broad-spectrum antimicrobial agent for topical application. II. Comparison with some other antimicrobial agents
Handwashing in a neonatal intensive care nursery: product acceptability and effectiveness of chlorhexidine gluconate 4% and triclosan 1%
Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli.
Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli.
Inhibition of beta-ketoacyl-acyl carrier protein synthase III (FabH) by acyl-acyl carrier protein in Escherichia coli.
Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis.
The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA
Transcriptional analysis of essential genes of the Escherichia coli fatty acid biosynthesis gene cluster by functional replacement with the analogous Salmonella typhimurium gene cluster
Genome-wide enrichment screening reveals multiple targets and resistance genes for triclosan in Escherichia coli
1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI)
Inhibitors of bacterial enoyl acyl carrier protein reductase (FabI): 2,9-disubstituted 1,2,3,4-tetrahydropyrido[3,4-b]indoles as potential antibacterial agents
Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure
Triclosan exposure increases triclosan resistance and influences taxonomic composition of benthic bacterial communities
3-substituted indole inhibitors against Francisella tularensis FabI identified by structure-based virtual screening
Discovery of 4-Pyridone derivatives as specific inhibitors of enoyl-acyl carrier protein reductase (FabI) with antibacterial activity against Staphylococcus aureus
Acyl-Acyl carrier protein regulates transcription of fatty acid biosynthetic genes via the FabT repressor in Streptococcus pneumoniae.
Exploring the interaction energies for the binding of hydroxydiphenyl ethers to enoyl-acyl carrier protein reductases
Mechanisms of antimicrobial action of antiseptics and disinfectants: an increasingly important area of investigation
Mass spectrometry-based systems approach for identification of inhibitors of Plasmodium falciparum fatty acid synthase
Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: exposure of a susceptible mutant strain to triclosan selects nfxB mutants overexpressing MexCD-OprJ
Defining and combating the mechanisms of triclosan resistance in clinical isolates of Staphylococcus aureus.
NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against beta-lactamase-producing strains.
Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H.
Efficacy of biocides used in the modern food industry to control salmonella enterica, and links between biocide tolerance and resistance to clinically relevant antimicrobial compounds.
Potential impact of increased use of biocides in consumer products on prevalence of antibiotic resistance.
Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs
The Francisella tularensis FabI enoyl-acyl carrier protein reductase gene is essential to bacterial viability and is expressed during infection
The MexJK efflux pump of Pseudomonas aeruginosa requires OprM for antibiotic efflux but not for efflux of triclosan.
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