Cariogenic potential in vitro in man and in vivo in the rat of lactate dehydrogenase mutants of Streptococcus Mutans
Authors: Christine P. Johnson, S.M. Gross, J.D. Hillman — Department of Microbiology, Forsyth Dental Center, Boston, MA
Journal: Archives of Oral Biology | Published: 1980 | Vol. 25: pp. 707–713
Abstract
Human tooth fragments transferred daily in sucrose-containing cultures of Streptococcus mutans strain BHT-2 developed visible white spots — the characteristic lesion of early dental caries — within 10 days. By contrast, tooth fragments exposed to an L(+)-lactate dehydrogenase (LDH)-deficient derivative of BHT-2 showed no visible lesions, even after 21 days of transfer.
More direct evidence for the non-cariogenic nature of LDH-deficient mutants was provided by gnotobiotic and conventional rat models, in which the mutants colonized the mouth to approximately the same extent as their parent, but produced a significantly lower incidence and severity of dental caries. Reversion studies suggested that single gene mutations are responsible for the deficiency in lactate dehydrogenase catalytic activity — which in turn is responsible for the observed decreases in acid production and cariogenic potential of the mutants.
Key Results
In Vitro
After 10 days of sequential transfer, the parent strain BHT-2 produced clearly visible white spot lesions on exposed tooth enamel. The LDH-deficient mutant JH145 produced no visible lesions even after 21 days. Terminal culture pH: 4.42 (parent) vs. 5.54 (LDH-deficient mutant).
Gnotobiotic Rat Model — Mean Caries Scores at 14 Weeks
| Strain | Mean Caries Score |
|---|---|
| BHT-2 (parent strain) | 216.0 |
| JH145R33 (wild-type revertant) | 203.6 |
| JH168 (LDH-deficient mutant) | 10.6 |
Conventional Rat Model — Mean Caries Scores at 14 Weeks
| Group | Mean Caries Score |
|---|---|
| BHT-2 (parent strain) | 128.1 |
| JH145 (LDH-deficient mutant) | 65.8 |
| Sham-infected control | 51.6 |
Significance
These results provide foundational evidence that bacterial acid production is the principal aetiologic agent in dental caries, and that LDH-deficient mutants — which colonize teeth normally but produce significantly less acid — have dramatically reduced cariogenic potential. This work established the basis for Streptococcus rattus JH145, one of the three strains in the ProBiora3® blend, as a safe probiotic candidate for caries prevention.
