Hydrolysis of triclosan monophosphate by dental plaque and selected species of oral micro-organisms

Triclosan monophosphate is a phosphorylated derivative of the antimicrobial agent, triclosan. In comparison with triclosan, it is highly soluble in aqueous solutions. It is hypothesized that, within the oral environment, triclosan monophosphate (which may be devoid of antimicrobial activity) will be hydrolyzed into triclosan by the action of microbial phosphatases. The liberated triclosan may then exert antimicrobial activity. To test this hypothesis, we designed experiments to measure the phosphatase activity of plaque and selected species of oral micro-organisms and to demonstrate hydrolysis of triclosan monophosphate. Tests comparing the minimal inhibitory concentration and minimal bactericidal concentration of triclosan and triclosan monophosphate were also undertaken. Dental plaque and the majority of the bacterial strains tested showed phosphatase activity against p-nitrophenyl phosphate which peaked below neutral pH (acid phosphatases) or above neutral pH (alkaline phosphatases). Dental plaque showed the highest levels of alkaline phosphatase (optimum at pH 9.0) and relatively high levels of acid phosphatase (optimum at pH 6.0 to 6.5). Dental plaque and selected species of micro-organisms were all capable of hydrolyzing triclosan monophosphate, albeit at different rates. The minimal inhibitory concentration and minimal bactericidal concentration values for triclosan monophosphate against eight bacterial strains were always considerably higher than the corresponding values for triclosan. Addition of triclosan monophosphate to an established culture (ca. 10(9) cfu/mL) of Capnocytophaga gingivalis growing continuously showed that triclosan monophosphate was rapidly hydrolyzed into triclosan with concomitant loss of total bacterial viability. It is therefore likely that triclosan monophosphate will be broken down into triclosan within the oral environment with concomitant antimicrobial activity.