Genetically modified Streptococcus mutans for the prevention of dental caries

@article{Hillman2004GeneticallyMS,
  title={Genetically modified Streptococcus mutans for the prevention of dental caries},
  author={Jeffrey D. Hillman},
  journal={Antonie van Leeuwenhoek},
  year={2004},
  volume={82},
  pages={361-366}
}
  • J. Hillman
  • Published 2004
  • Biology, Medicine
  • Antonie van Leeuwenhoek
There are many examples of positive and negative interactions between different species of bacteria inhabiting the same ecosystem. This observation provides the basis for a novel approach to preventing microbial diseases called replacement therapy. In this approach, a harmless effector strain is permanently implanted in the host's microflora. Once established, the presence of the effector strain prevents the colonization or outgrowth of a particular pathogen. In the case of dental caries… 
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TLDR
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References

SHOWING 1-10 OF 49 REFERENCES
Construction and Characterization of an Effector Strain of Streptococcus mutans for Replacement Therapy of Dental Caries
TLDR
The reduced pathogenic potential of BCS3-L1, its strong colonization potential, and its genetic stability suggest that this strain is well suited to serve as an effector strain in the replacement therapy of dental caries in humans.
Colonization of the Human Oral Cavity by a Streptococcus mutans Mutant Producing Increased Bacteriocin
TLDR
The results provide additional support for the role of bacteriocin production as an ecological determinant in colonization by S. mutans and indicate that a practical regimen for infection by an effector strain might be achieved for use in the replacement therapy of dental caries.
Colonization of the Human Oral Cavity by a Strain of Streptococcus mutans
TLDR
The efficient replacement of indigenous S. mutans by JH1001 in one subject lends support to the eventual application of replacement therapy to the prevention of dental caries and indicates the importance of host variability and infection regimen for superinfection by this strain of S. Mutans.
Adaptive Changes in a Strain of Streptococcus mutans during Colonisation of the Human Oral Cavity
TLDR
Results indicate that environmental factors operating in the oral cavity of human subjects select variants of S. mutans that are better adapted to proliferate in vivo.
Natural Genetic Transformation ofStreptococcus mutans Growing in Biofilms
TLDR
It is demonstrated that a peptide pheromone system controls genetic competence in S. mutans and that the system functions optimally when the cells are living in actively growing biofilms.
Prevalence of transformable Streptococcus mutans in human dental plaque
TLDR
Three serotypes of Streptococcus mutans serotypes c/e/f and d/g, freshly isolated from dental plaque, were screened for their ability to undergo genetic transformation to streptomycin resistance and two were found to be transformable.
Evidence that L-(+)-lactate dehydrogenase deficiency is lethal in Streptococcus mutans
TLDR
The results are interpreted as indicating that LDH deficiency is lethal in S. mutans under the cultivation conditions used in these experiments.
The use of bacterial interference to prevent infection.
TLDR
Strain 215 can survive in the pharynx during subsequent antibiotic therapy and can be recalled to dominance by such therapy, and seems remarkably stable in vivo.
Genetic diversity within Streptococcus mutans evident from chromosomal DNA restriction fragment polymorphisms
TLDR
The potential utility of genomic fingerprinting in studying the natural history of S. mutans infections in humans is demonstrated and it is found that mothers and their infants harbored only a few individual strains, suggesting that transmission of this organism is probably confined within discrete family cohorts.
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