Genetically modified Streptococcus mutans for the prevention of dental caries

  title={Genetically modified Streptococcus mutans for the prevention of dental caries},
  author={Jeffrey D. Hillman},
  journal={Antonie van Leeuwenhoek},
  • 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… 
Draft Genome Sequence of Oral Bacterium Streptococcus mutans JH 1140
Assembly of the S. mutans JH1140 genome has helped identify novel bacteriocins and provided further understanding of the effector strain BCS3-L1’s superior colonization properties that facilitated its development as a replacement therapy strain.
Virulence properties of Streptococcus mutans.
  • J. Banas
  • Biology
    Frontiers in bioscience : a journal and virtual library
  • 2004
This review focuses on the bacterial components that contribute to each of the major virulence properties of S. mutans and describes how these components work together in the development of dental caries.
A New gcrR-Deficient Streptococcus mutans Mutant for Replacement Therapy of Dental Caries
Findings demonstrate that MS-gcrR-def appears to be a good candidate for replacement therapy, and shows that the adhesion ability of the mutant increased relative to the wild type, especially in the early stage.
The mutacins of Streptococcus mutans: regulation and ecology.
As more S. mutans strains are sequenced, it is anticipated that additional mutacins with novel functions will be discovered, which may yield further insights into the ecological role ofmutacins within the oral biofilm.
Identification of genes associated with mutacin I production in Streptococcus mutans using random insertional mutagenesis.
The results suggest that mutacin I production is stringently controlled by diverse and complex regulatory pathways.
Genotyping and Phenotypic Analysis of Streptococcus mutans Isolates From Children With and Without Dental Caries
Within dental plaque, Streptococcus mutans produces acids from fermentable carbohydrates, decreasing the biofilm pH, causing enamel demineralization, and the ability of S. mutans to produce high levels of persisters may be a hallmark of cariogenicity.
Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials
The strain has significantly reduced cariogenicity owing to a deletion of the entire open reading frame for lactate dehydrogenase, and has excellent colonization potential through the production of a natural antibiotic called mutacin 1140.
Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains
The successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability are demonstrated.
Salivaricin E and abundant dextranase activity may contribute to the anti-cariogenic potential of the probiotic candidate Streptococcus salivarius JH.
Strain JH produces salivaricin E, a 32 aa lantibiotic with a mass of 3565.9 Da, which is responsible for the inhibition of S. mutans growth, and dextranase, an enzyme that hydrolyses (1 → 6)-α-D-glucosidic linkages, at levels higher than any other S. salivarius tested.
The vaccination approach to control infections leading to dental caries
The advances in understanding of the molecular mechanisms which underlie MS transmission, tooth colonization and virulence are discussed, and current strategies for anti-caries vaccination efforts with regard to important bacterial targets, routes, adjuvants and delivery systems for active and passive immunization are described.


Construction and Characterization of an Effector Strain of Streptococcus mutans for Replacement Therapy of Dental Caries
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
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
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
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
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
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
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.
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
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.