Triclosan was found to be a potent inhibitor of the F(H+)-ATPase of the oral pathogen
Streptococcus mutans and to increase proton permeabilities of intact cells. Moreover, it acted additively with
weak-acid transmembrane proton carriers, such as fluoride or sorbate, to sensitize glycolysis to acid
inhibition. Even at neutral pH, triclosan could inhibit glycolysis more directly as an irreversible inhibitor of
the glycolytic enzymes pyruvate kinase, lactic dehydrogenase, aldolase, and the phosphoeolpyruvate:sugar
phosphotransferase system (PTS). Cell glycolysis in suspensions or biofilms was inhibited in a pHdependent
manner by triclosan at a concentration of about 0.1 mmol/L at pH 7, approximately the lethal
concentration for S. mutans cells in suspensions. Cells in intact biofilms were almost as sensitive to triclosan
inhibition of glycolysis as were cells in suspensions but were more resistant to killing. Targets for
irreversible inhibition of glycolysis included the PTS and cytoplasmic enzymes, specifically pyruvate
kinase, lactic dehydrogenase, and to a lesser extent, aldolase. General conclusions are that triclosan is a
multi-target inhibitor for mutans streptococci, which lack a triclosan-sensitive FabI enoyl-ACP reductase,
and that inhibition of glycolysis in dental plaque biofilms, in which triclosan is retained after initial or
repeated exposure, would reduce cariogenicity. ?? 2006 NRC Canada.
