Replacement therapy for dental caries

Patent metadata

Field	Value
Publication number	US-9260488-B2
Application number	US-201314381524-A
Country	US
Kind code	B2
Filing date	Feb 22, 2013
Priority date	Feb 27, 2012
Publication date	Feb 16, 2016
Grant date	Feb 16, 2016

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.

First claim

What is claimed is:

1. An isolated recombinant Streptococcus mutans strain comprising:
(a) 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;
(b) a recombinant alcohol dehydrogenase polynucleotide; and
(c) 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.

2. The isolated recombinant Streptococcus mutans strain of claim 1 , wherein the lantibiotic comprising Formula I further comprises a Trp4insAla mutation or a ΔTrp4 mutation.

3. The isolated recombinant Streptococcus mutans strain of claim 1 , wherein the lantibiotic comprising Formula I further comprises the following amino acid substitutions: Abu8Ala, or Dhb14Ala, or both Abu8Ala and Dhb14Ala.

4. The isolated recombinant Streptococcus mutans strain of claim 1 , further comprising a mutation in a polynucleotide involved in ComE, ComC or both ComE and ComC synthesis such that expression of ComE, ComC, or both ComE and ComC is diminished by about 80% or more as compared to a wild-type S. mutans strain.

5. The isolated recombinant Streptococcus mutans strain of claim 1 , further comprising a mutation in a polynucleotide involved in D-amino acid synthesis such that expression of the D-amino acid is diminished by about 80% or more as compared to a wild-type Streptococcus mutans strain.

6. The isolated recombinant Streptococcus mutans strain of claim 5 , wherein the polynucleotide involved in D-amino acid synthesis is dal or a promoter for dal.

7. The isolated recombinant Streptococcus mutans strain of claim 1 , wherein the recombinant alcohol dehydrogenase polynucleotide is a Zymomonas mobilis alcohol dehydrogenase polynucleotide or a Streptococcus mutans alcohol dehydrogenase polynucleotide.

8. A method of reducing the incidence or severity of dental caries in a dental caries-susceptible host comprising administering orally to the host the isolated recombinant Streptococcus mutans strain of claim 1 in an amount effective for replacement of dental caries-causing Streptococcus mutans host strains in the oral cavity of the host.

9. The method of claim 8 , wherein the isolated recombinant Streptococcus mutans strain is contained in a mouthwash, toothpaste, chewing gum, floss, chewable tablet, food, or beverage.

10. A pharmaceutical composition for reducing the incidence or severity of dental caries comprising the isolated recombinant Streptococcus mutans strain of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Oragenics Inc
• Texas A & M Univ Sys
• Texas A&M University

Inventors

• Hillman Jeffrey D
• Smith James Leif
• Wilson-Stanford Shawanda R

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P1/02

  Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis · CPC title

• A61K35/744

  Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs · CPC title

• A61Q11/00

  Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses · CPC title

• C12N9/0006

  acting on CH-OH groups as donors (1.1) · CPC title