The Microbiology of Dental Caries

Caries defined

Dental caries- an infectious disease that damages the structures of teeth. The prevalence of dental caries (i.e., the percentage of persons with >1 decayed, missing, or filled teeth) in permanent teeth increases with age, from 26% among persons aged 5--11 years to 67% among persons aged 12--17 years and 94% for dentate adults (with >1 natural teeth) aged >18 years.

The original model

A more recent model

Criteria for Cariogenicity

An organism must acidogenic An organism must be aciduric An organism must exhibit tropism for teeth An organism must utilize refined sugar (sucrose)

(Newburn, 1983)

The caries culprits

The main microorganism involved in the initial caries process is S. mutans. S. sobrunis and lactobacillus are also involved, but must have s. mutans present to colonize. Sobrinus means distant cousin on mothers side. Lactobacillus produces lactic acid at higher concentrations than helpful bugs

Streptococcus mutans
What is it?

Streptococcus mutans
What is it? A gram + facultative anaerobe characterized by 8 serotypes, a-h.

Streptococcus mutans
What is it? A gram + facultative anaerobe characterized by 8 serotypes, a-h. Prevelance?

Streptococcus mutans
What is it? A gram + facultative anaerobe characterized by 8 serotypes, a-h. Prevelance? The most prevelant serotype in the USA is c.

Streptococcus mutans
What is it? A gram + facultative anaerobe characterized by 8 serotypes, a-h. Prevelance? The most prevelant serotype in the USA is c. Groups?

Carbohydrate Antigens

Carbohydrate heteropolymers that contain glucose and galactose. Antibody specificity Bind glucosyltransferase to bacterial cell

The Mutans Streptococcus

Species
S. mutans S. sobrinus S. cricetus S. rattus S. downei S. macacae

Serotype c,e,f d,g,h a b h c

Human Human

Source

Sometimes human, mostly rats and hamsters Sometimes humans, mostly rats Macaque monkey Macaque monkey

S. ferus

Rats

How does Strep mutans attatch to teeth and cause caries?

Biofilm Formation

Environment

Require a non-shedding Needs nutritionally rich media for growth. Optimum temp for growth is 37 C, or 25-42C. Low pH Transmission: Vertical and Horizontal

Transmission
Vertical
Parent to child

Horizontal
Non-parent same species transfer

Role of mutacin Window of infectivity

S. mutans structures

Adhesin

A surface structure or macromolecule that binds a bacterium to a specific surface. Antigen (Ag) I/II or SpaP

Attatches to salivary pellicle receptors, salivary agglutinins, and other bacteria. Also provides mechanism for binding of salivary agglutinin glycoprotein to the streptococcal cell surface-generates receptor for other bacteria to adhere. Enables P. gingivalis to adhere to streptococci, enabling secondary colonizers to be incorporated into plaque communities.

S. mutans structures

Extracellular enzymes

1. Gtf-I

Forms insoluble glucans with mostly 1,3 links between glucose polymers (mutans).
Forms water soluble glucans with mostly 1,6 links between glucose polymers (dextrans). Forms both water soluble and insoluble glucans. Forms water soluble fructose

2. Gtf-S

3. Gtf-SI

4. Ftf

S. mutans structures

Glucans

Tooth adherence Promotes aggregation Biofilm accumulation Retention of bacterial nutrients Some antibodies prevent GTF function and are protective.

Dextranases

Can convert glucan into glucose for glycolysis. Break down -1,6 linkages of glucose into -1,3 linkages. Glucans can serve as attachment mechanisms and energy stores.

LTA

Lipoteichoic acid is an amphipathic constituent of the gram-positive bacteria outer-envelope. Can stimulate inflammation-TLR2 Analgous to LPS in gram negative bacteria. May help in adherence Key in virulence. Area for possible vaccine?

Cell walls

Vaccines Against Dental Caries

Effective Vaccines

Identify the bad guy. Identify the best target to destroy the bad guy. Identify the component of the immune system that should be targeted.

Vaccines: Whole or part?

Early vaccinations involved patients swallowing boluses of killed S. mutans. This induced heart cross-reactive antibodies.

Cardiolipin (diphosphatidyl glycerol) Removed using a preadsorption technique

May no longer be a concern?

More recent efforts have focused on protein expression and secretion.

Effective Vaccines

Identify the bad guy. Identify the best target to destroy the bad guy. Identify the component of the immune system that should be targeted.

Effective Vaccines

Identify the bad guy. Identify the best target to destroy the bad guy. Identify the component of the immune system that should be targeted. Should NOT harm the host!

Role of IgA

Prevents colonization Key in vaccine development More IgA produced daily than any other immunoglulin. Finding ways to prolong the availability of antigens in the secretory IgA will improve dental caries vaccinations.

Vaccines

Ag I/II vaccine would prevent binding. Molecules that act as adjuvants, such as cholera toxin B and E coli. heat-liable toxin, improve the longevity of the IgA response to antigens from S. mutans. Recombinant strains methods also reduce cross-reactivity problems and help prolong IgA response as well.

Target Antigens

Subunit vaccination

Bacerial antigens
Proteins Target Gtf

Synthetic peptides

Enteric Pathway

Put antigens in a harmless enteric bacteria Natural proliferation in gut; greater power than capsules with the antigen Considerations Is the bug really harmelss? Plasmid vectors can encode resistance

Active or Passive?
Which is better? Active immunity will produce higher titers. Route? Oral and intranasal favored thus far.

Public considerations

1950s-4 vaccines; 1:10,000 autism 1980s-8 vaccines; 1/2,600 1990s-10 vaccines; 1/350 Today-13 vaccines, given in 33 shots before a child is 2 years of age 1/100 boys, 1/400 girls is diagnosed with autism

Considerations
Debate similar to fluoride? How would one more vaccine be received?

Thank You!