Weak acid effects and fluoride inhibition of glycolysis by Streptococcus mutans GS-5

Fluoride and a variety of other weak acids acted to reduce reversibily the acid tolerance of glycolysis by intact cells of Streptococcus mutans GS-5 as shown by higher final pH values in acid-drop experiments with glucose in excess. The order of effectiveness was fluoride > indomethacin > ibuprofen > ketoprofen > salicylate > sorbate > cinnamate > p-hydroxybenzoate > benzoate > ascorbate. Only fluoride also acted as an inhibitor of the glycolytic enzyme enolase. However, enolase in permeabilized cells was also inhibited by acidification with a sharp drop-off in activity between pH 6 and 5. It was proposed that the weak acids, including fluoride, acted to reduce glycolytic acid tolerance by enhancing cytoplasmic acidification and thereby inhibiting enzymes such as enolase. The potencies of the acids could not be predicted accurately from knowledge of pKa values, octanol-water partition coefficients, and molecular weights. It was concluded that their modes of action in acid sensitization involved perturbations of membrane function in addition to their acting as transmembrane carriers of protons. Methylparaben (methyl ester of p-hydroxybenzoate) was also a sensitizer but was less effective than the parent acid.