INHIBITION OF STREPTOCOCCAL GROWTH, F-ATPASE AND PYROPHOSPHATASE BY DIPHOSPHONATES

1-Hydroxyethane-1,1-diphosphonate (EHDP) and a variety of other diphos phonates, and also pyrophosphate, at millimolar levels were found to i nhibit the growth of Streptococcus mutans GS-5. Inhibition appeared to be due mainly to chelation of Mg2+ and could be readily reversed thro ugh addition of Mg2+, or less effectively, by other divalent cations. The trianionic forms of the diphosphonates or pyrophosphate were more effective inhibitors than the dianionic forms. Diphosphonates and pyro phosphate did not inhibit glycolysis by S. mutans, assayed in terms of glucose utilization, or arginolysis by Streptoccus rattus FA-1, assay ed in terms of ammonia production. However, they did act as buffers to moderate pH changes. Diphosphonates also were inhibitors of the F-ATP ase of S. mutans by complex mechanisms only partly reversible with div alent cations. They also were inhibitors of the pyrophosphatase of the organism. However, intact cells were impermeable to the compounds, an d inhibition of cytoplasmic or membrane enzymes did not appear to be i nvolved in growth inhibition.