Disease relevance of triclosan

• Triclosan-resistant Staphylococcus aureus [1].
• Expression of YgaA complemented the fabI(ts) defect in E. coli and conferred complete triclosan resistance [2].
• We compared the consequences of INH treatment of Mycobacterium tuberculosis (MTB) with two inhibitors having well-defined targets: triclosan (TRC), which inhibits InhA; and thiolactomycin (TLM), which inhibits KasA [3].
• Topical triclosan treatment of atopic dermatitis [4].
• Dental plaque microcosms were established under a feast-famine regimen within constant-depth film fermentors and exposed four times daily postfeeding to a triclosan (TR)-containing rinse (dentifrice) (TRD) [5].

Psychiatry related information on triclosan

• This investigation examined the antimicrobial effects of a new liquid triclosan/copolymer dentifrice (test) formulation that demonstrated significant inhibition of oral malodor in previous organoleptic clinical studies [6].

High impact information on triclosan

• The antimicrobial biocide triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol] potently inhibits the growth of Plasmodium falciparum in vitro and, in a mouse model, Plasmodium berghei in vivo [7].
• Transferable resistance to triclosan in MRSA [8].
• Humans, the vertebrate host for the malarial parasite utilize type I FAS, which is not inhibited by triclosan [9].
• In direct contrast to the delayed-death phenotype associated with poisoning of the apicoplast using certain other drugs, the rapid and striking action of triclosan suggests the possibility of developing new drug(s) for the treatment of malaria [9].
• Triclosan that is used as an antibacterial agent against fatty acid synthesis type II 2-enoyl thioester reductases inhibited growth of FabI overexpressing mutant yeast cells but was not able to inhibit respiratory growth of the ETR2- or ETR1-complemented mutant yeast cells [10].

Chemical compound and disease context of triclosan

• Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene [11].
• CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents [12].
• Therefore, the effect of 0.3% triclosan added to non-fluoride and fluoride toothpaste was tested in an in vitro model, in which bovine enamel specimens were to be demineralized by acids produced in overlaying Streptococcus mutans suspensions [13].
• Of the agents discussed, the greatest effect on the reduction of plaque and gingivitis can be expected from chlorhexidine, essential oils, and triclosan-containing products [14].
• Using the biocide triclosan as a selective agent, several triclosan-resistant mutants of a susceptible Pseudomonas aeruginosa strain were isolated [15].

Biological context of triclosan

• 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 [16].
• Both the introduction of a plasmid expressing the safabI gene or a missense mutation in the chromosomal safabI gene led to triclosan resistance in S. aureus; however, these strains did not exhibit cross-resistance to hexachlorophene [11].
• Molecular genetic studies with strains of Escherichia coli resistant to triclosan, an ingredient of many anti-bacterial household goods, have suggested that this compound works by acting as an inhibitor of enoyl reductase (ENR) and thereby blocking lipid biosynthesis [17].
• Antibacterial product use did not lead to a significant increase in antimicrobial drug resistance after 1 year (odds ratio 1.33, 95% confidence interval 0.74-2.41), nor did it have an effect on bacterial susceptibility to triclosan [18].
• The compounds exploit beta-lactamases to release triclosan through hydrolysis of the beta-lactam ring [19].

Anatomical context of triclosan

• These 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 [20].
• Effect of triclosan on the development of bacterial biofilms by urinary tract pathogens on urinary catheters [21].
• This suggests that, in C. gingivalis, TMP may diffuse into the cell wall more easily than triclosan and then be converted to triclosan by phosphatase activity within the cell wall complex, where it may give rise to high localized concentrations and subsequent cell damage [22].
• Previously, we reported that triclosan reduces the production of the inflammatory mediators in gingival fibroblasts [23].
• This very low solubility can hamper its biological activity in the oral cavity, which could explain the mixed clinical results obtained from triclosan toothpaste trials [24].

Associations of triclosan with other chemical compounds

• Although all three compounds inhibit mycolic acid synthesis, treatment with INH and TLM, but not with TRC, results in the accumulation of ACP-bound lipid precursors to mycolic acids that were 26 carbons long and fully saturated [3].
• Specific inhibitors of the type II pathway, thiolactomycin and triclosan, have been reported to target this Plasmodium pathway [25].
• Following hydrolysis of possible conjugates, triclosan is extracted with n-hexane/acetone, partitioned into alcoholic potassium hydroxide, and converted into its pentafluorobenzoyl ester [26].
• We present here the results for one of the beta-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold [27].
• The site of action of isoniazid, used in the treatment of tuberculosis for 50 years, and the consumer antimicrobial agent triclosan were revealed recently to be the enoyl-ACP reductase of the type II FAS [28].

Gene context of triclosan

• (i) NB2001 is a substrate for TEM-1 beta-lactamase, forming triclosan with a second-order rate constant (k(cat)/K(m)) of greater than 77,000 M-1 s-1 [27].
• Studies of 3-OH-BaP sulfonation by expressed human SULT1A1*1, SULT1A1*2, SULT1B1, and SULT1E1 showed that triclosan inhibited the activities of each of these purified enzymes with IC50 concentrations between 2.09 and 7.5 microM [29].
• The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2% [30].
• Moreover, enhanced COX-2 mRNA repression was observed with triclosan and CPC in comparison to triclosan alone in IL-1beta and TNF-alpha stimulated cells [31].
• Further analysis of cell signaling mechanisms of triclosan and CPC indicates that nuclear factor-kappa B (NF-kappaB) and not p38 mitogen-activated protein kinase (MAPK) signaling may be impaired in the presence of triclosan and CPC [31].

Analytical, diagnostic and therapeutic context of triclosan

• These results indicate that triclosan suppresses rat mammary carcinogenesis by inhibiting FAS and suggest that FAS is a promising molecular target for breast cancer chemoprevention [32].
• Gel filtration and mass spectrometry show that inhibition by triclosan is reversible [33].
• Similarly 9 of 13 triclosan eluting stents showed no viable organisms upon recovery and the remaining 4 showed significantly fewer organisms than controls [34].
• HPLC was used to determine the triclosan concentration in urine draining from models that had been fitted with triclosan-inflated silicone catheters [21].
• Uncured MDPB revealed antibacterial activity against S. mutans and six other species of oral streptococci, with the minimum inhibitory concentration for S. mutans being comparable with that of triclosan [35].

References