Archives of Microbiology

, Volume 155, Issue 1, pp 22–27 | Cite as

Inhibition of proton-translocating ATPases of Streptococcus mutans and Lactobacillus casei by fluoride and aluminum

  • Michael G. Sturr
  • Robert E. Marquis
Original Papers


One of the major effects of fluoride on oral bacteria is a reduction in acid tolerance, and presumably also in cariogenicity. The reduction appears to involve transport of protons across the cell membrane by the weak acid HF to dissipate the pH gradient, and also direct inhibition of the F1F0, proton-translocating ATPases of the organisms, especially for Streptococcus mutans. This direct inhibition by fluoride was found to be dependent on aluminum. The dependence on aluminum was indicated by the protection against fluoride inhibition afforded by the Al-chelator deferoxamine and by loss of protection after addition of umolar levels of Al3+, which were not inhibitory for the enzyme in the absence of fluoride. The F1 form of the enzyme dissociated from the cell membrane previously had been found to be resistant to fluoride in comparison with the F1F0 membrane-associated form. However, this difference appeared to depend on less aluminum in the F1 preparation in that the sensitivity of the F1 enzyme to fluoride could be increased by addition of umolar levels of Al3+. The effects of Al on fluoride inhibition were apparent when enzyme activity was assayed in terms of phosphate release from ATP or with an ATP-regenerating system containing phosphoenolpyruvate, pyruvate kinase, NADH and lactic dehydrogenase. Also, Be2+ but not other metal cations, e.g. Co2+, Fe2+, Fe3+, Mn2, Sn2+, and Zn2+, served to sensitize the enzyme to fluoride inhibition. The differences in sensitivities of enzymes isolated from various oral bacteria found previously appeared also to be related to differences in levels of Al. Even the fluoride-resistant enzyme of isolated membranes of Lactobacillus casei ATCC 4646 could be rendered fluoride-sensitive through addition of Al3+. Thus, the F1F0 ATPases of oral bacteria were similar to E1E2 ATPases of eukaryotes in being inhibited by Al-F complexes, and the inhibition presumably involved formation of ADP-Al-F inf3 sup- complexes during catalysis at the active sites of the enzymes.

Key words

Fluoride Aluminum F1F0 ATPase Oral bacteria Streptococcus mutans Lactobacillus casei 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ackrill P, Day JP (1984) Therapy of aluminum overload (II). Contrib Nephrol 38:78–80Google Scholar
  2. Bender GR, Marquis RE (1987) Membrane ATPases and acid tolerance of Actinomyces viscosus and Lactobacillus casei. Appl Environ Microbiol 53:2124–2128Google Scholar
  3. Bender GR, Sutton SVW, Marquis RE (1986) Acid tolerance, proton permeabilities, and membrane ATPases of oral streptococci. Infect Immun 53:331–338Google Scholar
  4. Duckworth RM, Morgan SN, Murray AM (1987) Fluoride in saliva and plaque following use of fluoride-containing mouthwashes. J Dent Res 66:1730–1734Google Scholar
  5. Ekstrand J, Fejerskov O, Silverman LM (1988) Fluoride in dentistry. Munksgaard, CopenhagenGoogle Scholar
  6. Geddes DAM, Rolla G (1988) Fluoride in saliva and dental plaque. In: Ekstrand J, Fejerskov O, Silverman LM (eds) Fluoride in dentistry. Munksgaard, CopenhagenGoogle Scholar
  7. Gutknecht J, Walter A (1981) Hydrofluoride and nitric acid transport through lipid bilayer membranes. Biochim Biophys Acta 644:153–156Google Scholar
  8. Kleber CJ, Putt MS (1984) Aluminum and dental caries a review of the literature. Clin Prevent Dent 6:14–25Google Scholar
  9. Lunardi J, Dupuis A, Garin J, Issartel J-P, Michel L, Chabre M, Vignais PV (1988) Inhibition of H+-transporting ATPase by formation of a tight nucleoside diphosphate-fluoroaluminate complex at the catalytic site. Proc Natl Acad Sci USA 85:8958–8962Google Scholar
  10. Marquis RE (1990) Diminished acid tolerance of plaque bacteria caused by fluoride. J Dent Res 69:672–675Google Scholar
  11. Missiaen L, Wuytack F, De Smedt H, Vrolix M, Casteels R (1988) AlF4 reversibly inhibits ‘P’-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase. Biochem J 253:827–833Google Scholar
  12. Robinson JD, Davis RL, Steinberg M (1986) Fluoride and beryllium interact with the (Na+K)-dependent ATPase as analogs of phosphate. J Bioenerg Biomembr 18:521–531Google Scholar
  13. Senior AE, Downie JA, Cox GB, Gibson F, Langman L, Fayle DRH (1979) The uncA gene codes for the alpha-subunit of the adenosine triphosphatase of Escherichia coli. Biochem J 180:103–109Google Scholar
  14. Sternweis PC, Gilman AG (1982) Aluminum: A requirement for activation of the regulatory component of the adenylate cyclase by fluoride. Proc Natl Acad Sci USA 79:4888–4891Google Scholar
  15. Sutton SVW, Bender GR, Marquis RE (1987) Fluoride inhibition of the proton-translocating ATPases of oral bacteria. Infect Immun 55:2597–2603Google Scholar
  16. Womack FC, Colowick SP (1979) Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations. Proc Natl Acad Sci USA 76:5080–5084Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Michael G. Sturr
    • 1
    • 2
  • Robert E. Marquis
    • 1
    • 2
  1. 1.Department of Microbiology/ImmunologyThe University of RochesterRochesterUSA
  2. 2.Department of Dental ResearchThe University of RochesterRochesterUSA

Personalised recommendations