Dental caries (normally known as tooth decay) is the damage to a tooth when decay-causing bacteria in the mouth make acids that attack the tooth's surface, corroding the enamel. This can eventually lead to cavities in the tooth and if not treated properly can cause pain, infection and even loss of the tooth.
Biofilm engineering is a novel approach in dental medicine that targets to replace/replenish the oral microbiota by providing cost-effective augmentation of conventional treatment strategies of oral health problems like caries. Hillman et. al. used this approach to construct an effector strain of oral microbial pathogen Streptococcus mutans that can be used for replacement therapy of dental caries. Note that Streptococcus mutans is the chief causative agent of dental caries.
The effector strain, called BCS3-L1 was genetically engineered by using recombinant DNA technology to delete the gene encoding lactate dehydrogenase (ldh), rendering it incapable of producing lactic acid. To rectify for any possible metabolic imbalance due to ldh gene deletion, a supplemental alcohol dehydrogenase gene from Zymomonas mobilis was substituted in place of the deleted ldh gene (ldh ORF, basically). The resulting clone , BCS3-L1, produced virtually no detectable lactic acid when grown on different carbon sources. Total acid production was also significantly less due to increased ethanol and acetoin production.
Additionally, the strain was also designed to synthesize a higher amount of a novel antibiotic peptide called mutacin 1140 providing a strong selective advantage over most other strains of Streptococcus mutans. In vitro and in vivo (rodent models), BCS3-L1 was genetically stable and showed no apparent negative side effects even during prolonged colonization. No gross or microscopic abnormalities of major organs were associated with oral colonization of rats with BCS3-L1 for 6 months. These primary results are indicative of the potential that even a single application of BCS3-L1 effector strain to human patients could result in permanent implantation, hence displacing over time the indigenous, caries causing S. mutans strains.
1.Hillman JD. Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie Van Leeuwenhoek. 2002;82(1-4):361-366.
2. Hillman JD, Brooks TA, Michalek SM, Harmon CC, Snoep JL, van Der Weijden CC. Construction and characterization of an effector strain of Streptococcus mutans for replacement therapy of dental caries. Infect Immun. 2000;68(2):543-549. doi:10.1128/iai.68.2.543-549.2000