Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. S. Mutans converts sugar that we eat into lactic acid, which in turn causes demineralization of teeth and hence, tooth decay.
A small biotech company called Oragenics has developed a genetically modified version of S. mutans that “produces absolutely no detectable lactic acid”.
Yesterday, Oragenics announced that it had received permission from the U.S. Food and Drug Administration to conduct Phase I clinical trials of their genetically modified bacteria.
The co indicates that if all goes as planned, people will only require a single 5 minute treatment to avoid tooth decay. A dentist would apply the modified bacteria to their teeth, and the patients would then have lifelong protection from tooth decay.
More details –
The original project plan called for investigation and exploitation of the following four features of S. mutans:
1. The ability to produce lactic acid
2. Extracellular polysaccharide biosynthesis responsible for trapping acid near tooth surfaces
3. The production of cell surface adhesins that mediate attachment to tooth enamel
4. The synthesis of mutacin antibiotic that protects the organisms habitat on tooth surfaces from competing bacteria
The first attempt involved allelic exchange of the luxS structural gene with a mutant gene carried on a suicide vector.
The researchers seem to have abandoned the above approach, and instead focused on ways to inhibit lactic acid production. The solution that they hit upon involves the tweaking of the metabolic pathway of this (new) strain so as to produce ethanol (2C2H5OH) instead of lactic acid (2C3H6O3).
Representations made by Oragenics to the Recombinant DNA Advisory Committee of the NIH can be found at this site. The aforementioned document has some very detailed information, and includes these coments:
A2JM is a naturally occurring S. mutans strain, originally isolated from a human subject, which has been genetically modified to reduce the pathogenic potential of and increased the colonization potential of S. mutans. A2JM has also been genetically modified to be completely dependent on environmental D-alanine for growth. Instead of lactic acid, A2JM makes the neutral compounds ethanol and acetone in amounts comparable to other microorganisms that colonize the human oral cavity. Preclinical studies suggested that A2JM is well suited to serve as an effector strain in the replacement therapy of dental caries.
Even more details —
One of the researchers, J. D. Hillman, published a paper in 2000, that described the modification process:
Recombinant DNA methods were used to make the Streptococcus mutans supercolonizing strain, JH1140, lactate dehydrogenase deficient by deleting virtually all of the ldh open reading frame (ORF). To compensate for the resulting metabolic imbalance, a supplemental alcohol dehydrogenase activity was introduced by substituting the adhB ORF from Zymomonas mobilis in place of the deleted ldh ORF. The resulting clone, BCS3-L1, was found to produce no detectable lactic acid during growth on a variety of carbon sources, and it produced significantly less total acid due to its increased production of ethanol and acetoin.
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Thank God!
This discovery can’t be good news for dentists.