Idea

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

Image credit: Kukski

Darko Savic Aug 02, 2020

Summary

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. Voila, no more dentist.

Process
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.
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)
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.
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.

virology genetic engineering

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General comments

Povilas S7 months ago

Darko Savic8 months ago

Darko Savic9 months ago

Shubhankar Kulkarni9 months ago

Jamila 9 months 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.

IDEA