Triclosan targets lipid synthesis

@article{McMurry1998TriclosanTL,
  title={Triclosan targets lipid synthesis},
  author={Laura M. McMurry and Margret Oethinger and Stuart B. Levy},
  journal={Nature},
  year={1998},
  volume={394},
  pages={531-532}
}
Triclosan is a broad-spectrum antibacterial and antifungal agent,, which acts by previously undetermined mechanisms, that is used in products such as antiseptic soaps, toothpastes, fabrics and plastics. Here we show that triclosan blocks lipid synthesis in Escherichia coli, and that mutations in, or overexpression of, the gene fabI (which encodes enoyl reductase, involved in fatty acid synthesis) prevents this blockage. This is, to our knowledge, the first evidence that triclosan acts on a… 
Microbiology: A triclosan-resistant bacterial enzyme
TLDR
A unique triclosan-resistant flavoprotein, FabK, is described that can also catalyse this reaction in Streptococcus pneumoniae, and has implications for the development of FabI-specific inhibitors as antibacterial agents.
Molecular basis of triclosan activity
TLDR
It is found that triclosan acts as a site-directed, very potent inhibitor of the enzyme by mimicking its natural substrate.
Broad Spectrum Antimicrobial Biocides Target the FabI Component of Fatty Acid Synthesis*
TLDR
Results contradict the view that these compounds directly disrupt membranes and suggest that their widespread use will select for resistant bacterial populations.
Triclosan: a widely used biocide and its link to antibiotics.
TLDR
There is a link between triclosan and antibiotics, and the widespread use of tricrosan-containing antiseptics and disinfectants may indeed aid in development of microbial resistance, in particular cross-resistance to antibiotics.
From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria.
TLDR
Some elements of the optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component delivered highly specific, potent, and nonbiocidal new FabI inhibitors.
Triclosan: An Update on Biochemical and Molecular Mechanisms
TLDR
This review presents a summary of the biochemical alterations pertaining to T CS exposure, with special emphasis on the diverse molecular pathways responsive to TCS that have been elucidated during the present decade.
Structural basis and mechanism of enoyl reductase inhibition by triclosan.
TLDR
The data provide a molecular mechanism for the antibacterial activity of triclosan and substantiate the hypothesis that its activity results from inhibition of a specific cellular target rather than non-specific disruption of the bacterial cell membrane.
Overexpression of marA, sod, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli
TLDR
It is reported here that overexpression of the multidrug efflux pump locus acrAB, or of marA or so&, both encoding positive regulators of UCYAB, decreased susceptibility to triclosan 2-fold and deletion of the acRAB locus increased susceptibility approximately IO-fold.
Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics
TLDR
Three compounds target the FabI enoyl-ACP reductase step; isoniazid, a clinically used antituberculosis drug, triclosan, a widely used consumer antimicrobial, and diazaborines, and the mechanisms of action of these compounds, as well as the potential development of new drugs targeted against this pathway are discussed.
...
...

References

SHOWING 1-8 OF 8 REFERENCES
Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis.
TLDR
Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the Nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of Inh A.
Triclosan: applications and safety.
Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline
Increasing levels of resistance to tetracycline and to a number of other unrelated antibiotics, including chloramphenicol, beta-lactams, puromycin, and nalidixic acid, occurred in Escherichia coli
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.
TLDR
Both reductase activities of the FabI protein are inhibited by physiologically relevant concentrations of palmitoyl-CoA, which might be important in regulating endogenous fatty acid biosynthesis in E. coli in the presence of exogenous fatty acids.
Zinc citrate/Triclosan: a new anti-plaque system for the control of plaque and the prevention of gingivitis: short-term clinical and mode of action studies.
  • D. Cummins
  • Medicine, Biology
    Journal of clinical periodontology
  • 1991
TLDR
A dentifrice based upon the additive anti-plaque effects of zinc citrate and Triclosan has been developed and optimised for clinical activity and the system has the potential to give a gingival health benefit in a 6-month unsupervised brushing study.
Methods for general and molecular bacteriology
Methodology for General and Molecular Microbiology Morphology Light microscopy Determinative and cytological light microscopy Electron microscopy Cell fractionation Antigen-antibody reactions Growth:
Sequences of the envM gene and of two mutated alleles in Escherichia coli.
TLDR
Comparison of the EnvM amino acid sequence with sequences available in databases showed significant homology with the family of short-chain alcohol dehydrogenases, which is totally absent in S. typhimurium.