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Eradicate oral bacteria with bacteriophage viruses and replace them with genetically modified, protective strains

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Darko Savic
Darko Savic Aug 02, 2020
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Find and isolate the bacteriophage viruses that target the pathogen bacteria of the mouth. Use the bacteriophages to eradicate the pathogen species. Seed the mouth with beneficial bacteria that have been engineered to kill and outcompete the pathogen species.


No more dentists.

How it works
  1. Figure out a way to find the bacteriophages of interest. For example find people with far below average incidence of oral infections (caries, periodontal disease) induced by oral biofilms.
  2. From their saliva Isolate bacteriophages that target the main disease-causing culprits such as Streptococcus Mutans, Streptococcus Sobrinus, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, and Eikenella corrodens)
  3. Create a mouthwash-like medium that is used to inoculate these isolated bacteriophages into the patient's mouth. Give it sufficient time to kill the bacteria.
  4. Inoculate the patient's mouth with beneficial bacterial species that have been engineered with an advantage which allows them to outcompete the pathogen species
Bacteria engineered to kill the pathogen species

Hillman developed ProBiora3, a probiotic mouthwash that contains three bacterial strains called streptococcus oralis KJ3, streptococcus uberis KJ2, and streptococcus rattus JH145. S. oralis and s. uberis both produce hydrogen peroxide; in vitro studies have shown that S. oralis and s. uberis are able to deplete pathogenic bacteria known to cause periodontal disease with the use of hydrogen peroxide. S. rattus JH145 is a lactate dehydrogenase deficient strain that is able to compete with s. mutans. Plaque derived from healthy sites is abundantly colonized with s. oralis and s. uberis. Whereas, plaque derived from diseased sites lacked s. oralis and s. uberis.

Future potential
  • this could be a biotech startup worthy direction
  • the same concept can be applied to many other persistent pathogen bacteria (C. difficile, H. pylori, etc)
  • good research potential

[1]Szafrański, Szymon P et al. “The use of bacteriophages to biocontrol oral biofilms.” Journal of biotechnology vol. 250 (2017): 29-44. doi:10.1016/j.jbiotec.2017.01.002

[2]Loesche WJ. Microbiology of Dental Decay and Periodontal Disease. In: Medical Microbiology. 4th ed. University of Texas Medical Branch at Galveston, Galveston (TX); 1996.

[3]Hillman, Jeffrey D., et al. "Safety assessment of ProBiora3, a probiotic mouthwash: subchronic toxicity study in rats." International journal of toxicology, 28.5, 2009, pp. 357-367.

[4]Hillman, J. D., S. S. Socransky, and Myra Shivers. "The relationships between streptococcal species and periodontopathic bacteria in human dental plaque." Archives of Oral Biology, 30.11-12, 1985, pp. 791-795.

[5]Hillman, J. D., et al. "A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries." Journal of applied microbiology, 107.5, 2009, pp. 1551-1558.

[6]Socransky, S. S., et al. "Associations between microbial species in subgingival plaque samples." Oral microbiology and immunology, 3.1, 1988, pp. 1-7.

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General comments

Povilas S
Povilas S4 years ago
Hydrogen peroxide is acidic. Acidic mouth pH is associated with caries either because acid degrades the enamel directly or because harmful bacteria thrive in more acidic pH. Probably both. It sounds a bit paradoxical that this could help.
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Darko Savic
Darko Savic4 years ago
I've been experimenting with this idea and it seems to be working pretty well:) instead of bacteriophages, I do the eradication stage with a mouthwash called ProntOral from Braun. It's designed to decolonize MRSA, ESBL, VRE. Safe to say it's pretty harsh. Half an hour later I seed the mouth with ProbioraPlus (streptococcus oralis KJ3, streptococcus uberis KJ2, and streptococcus rattus H145)
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Darko Savic
Darko Savic4 years ago
Are there any populations (tribes, etc) known to have extremely low incidence of oral diseases?
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Shubhankar Kulkarni
Shubhankar Kulkarni4 years ago
I think dental caries arise predominantly due to lack of sufficient immune response rather than the presence or absence of specific microorganisms. Maintaining immunity may, therefore, be the best way to go. We may extrapolate this issue to all pathogens like acne- or other disease-causing bacteria residing on the skin and we need to carry out the above-mentioned process for all the human organs typically associated with pathogens. This seems like a time- and resource-consuming process. On the other hand, maintaining immunity is a one-shot solution to all such problems.
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Jamila 4 years ago
Many bacteria including S. mutans are challenged by bacteriophages in the environment. As a result, bacteria have developed a defence mechanism against bacteriophages called the CRISPR-Cas system. Several studies have shown that most s. mutans strains possess the CRISPR-Cas system and thus can avoid an attack by specific bacteriophages like phage M102. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316486/) However, some phages have also developed mechanisms to avoid the bacterial CRISPR-Cas system by producing anti-CRISPRs. (https://science.sciencemag.org/content/369/6499/54) Perhaps there are bacteriophages that naturally possess specific anti-CRISPRs that can reduce caries-causing bacteria, and these specific phages could be selected for the mouthwash or anti-CRISPR proteins could be added to the mouthwash separately and this may enhance the effectiveness of the bacteriophages against caries-causing bacteria.
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