Replacement therapy for dental caries
Inventors
Hillman, Jeffrey D. • SMITH, JAMES LEIF • Wilson-Stanford, Shawanda R.
Assignees
Texas A&M University System • Oragenics Inc • Texas A&M University
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Publication Number
US-9260488-B2
Publication Date
2016-02-16
Expiration Date
Abstract
The invention provides recombinant Streptococcus mutans strains that can be used to improve oral health. An embodiment of the invention provides a method of reducing the incidence or severity of dental caries in a dental caries-susceptible host comprising administering orally to the host an isolated recombinant S. mutans strain of the invention in an amount effective for replacement of dental caries-causing S. mutans host strains in the oral cavity of the host. The isolated recombinant S. mutans strain 10 can be contained in a mouthwash, toothpaste, chewing gum, floss, chewable tablet, food, or beverage.
Core Innovation
The disclosure relates to replacement-therapy formulations for dental caries using isolated recombinant Streptococcus mutans strains. The recombinant strains have diminished lactic acid expression by about 80% or more compared to a wild-type Streptococcus mutans strain, and this attenuation is achieved by a mutation in a polynucleotide involved in lactic acid synthesis such that expression of lactic acid is diminished.
The isolated recombinant Streptococcus mutans strain further includes a recombinant alcohol dehydrogenase polynucleotide and a recombinant polynucleotide encoding a lantibiotic comprising Formula I. The lantibiotic includes specific amino-acid mutations, including a Phe1Ile mutation or a Phe1Gly mutation, a Trp4Ala mutation, a Dha5Ala mutation, an Arg13Asp mutation, or combinations of two or more of these mutations.
The disclosure also includes additional recombinant attenuations through dependent claim limitations that further diminish expression of other factors, including mutations that reduce expression of ComE and/or ComC by about 80% or more and mutations that diminish D-amino acid expression by about 80% or more. The replacement-therapy framing is directed to displacing dental caries-causing Streptococcus mutans strains in a dental caries-susceptible host to reduce the incidence or severity of dental caries.
Claims Coverage
The independent claim covers an isolated recombinant Streptococcus mutans strain with three core inventive features: lactic-acid-synthesis attenuation, a recombinant alcohol dehydrogenase polynucleotide, and a lantibiotic comprising Formula I with specified amino-acid mutations.
Lactic-acid-synthesis mutation with diminished lactic acid expression
An isolated recombinant Streptococcus mutans strain comprising a mutation in a polynucleotide involved in lactic acid synthesis such that expression of lactic acid is diminished by about 80% or more as compared to a wild-type S. mutans strain.
Recombinant alcohol dehydrogenase polynucleotide
An isolated recombinant Streptococcus mutans strain comprising a recombinant alcohol dehydrogenase polynucleotide.
Lantibiotic comprising Formula I with specified mutations
An isolated recombinant Streptococcus mutans strain comprising a recombinant polynucleotide encoding a lantibiotic comprising Formula I, wherein the following mutations are present: a Phe1Ile mutation or a Phe1Gly mutation; a Trp4Ala mutation; a Dha5Ala mutation; an Arg13Asp mutation; or combinations of two or more of these mutations.
The inventive concept combines strong diminution of lactic acid expression, inclusion of a recombinant alcohol dehydrogenase polynucleotide, and encoding a lantibiotic comprising Formula I with specified amino-acid mutations at positions including Phe1, Trp4, Dha5, and Arg13, with combinations permitted.
Stated Advantages
Reducing the incidence or severity of dental caries.
Documented Applications
A pharmaceutical composition comprising an isolated recombinant Streptococcus mutans strain and a pharmaceutically acceptable carrier to reduce the incidence or severity of dental caries.
Orally administering an isolated recombinant Streptococcus mutans strain in an amount effective to replace dental caries-causing Streptococcus mutans strains in the oral cavity of a dental caries-susceptible host, thereby reducing the incidence or severity of dental caries.
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