The Microbiology of Dental Caries. Caries defined Dental caries- an infectious disease that damages...

The Microbiology of The Microbiology of Dental CariesDental Caries

Caries definedCaries defined

Dental cariesDental caries- an infectious disease - an infectious disease that damages the structures of teeth.that damages the structures of teeth.

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

The original modelThe original model

A more recent modelA more recent model

Criteria for CariogenicityCriteria for Cariogenicity

An organism must acidogenicAn organism must acidogenic An organism must be aciduricAn organism must be aciduric An organism must exhibit tropism for An organism must exhibit tropism for

teethteeth An organism must utilize refined sugar An organism must utilize refined sugar

(sucrose)(sucrose)

(Newburn, 1983) (Newburn, 1983)

The caries culpritsThe caries culprits

The main microorganism involved in the The main microorganism involved in the initial caries process is S. mutans.initial caries process is S. mutans.

S. sobrunis and lactobacillus are also S. sobrunis and lactobacillus are also involved, but must have s. mutans present involved, but must have s. mutans present to colonize.to colonize.

Sobrinus means “distant cousin on Sobrinus means “distant cousin on mother’s side”. mother’s side”.

Lactobacillus produces lactic acid at Lactobacillus produces lactic acid at higher concentrations than “helpful” bugshigher concentrations than “helpful” bugs

Streptococcus mutansStreptococcus mutans

What is it?What is it?



A gram + facultative anaerobe A gram + facultative anaerobe characterized by 8 serotypes, a-h.characterized by 8 serotypes, a-h.




Prevelance?Prevelance?





The most prevelant serotype in the The most prevelant serotype in the USA is c.USA is c.





The most prevelant serotype in the The most prevelant serotype in the USA is c.USA is c.

Groups?Groups?

Carbohydrate AntigensCarbohydrate Antigens

Carbohydrate heteropolymers that Carbohydrate heteropolymers that contain glucose and galactose.contain glucose and galactose.

Antibody specificityAntibody specificity Bind glucosyltransferase to bacterial Bind glucosyltransferase to bacterial

cellcell

The Mutans The Mutans StreptococcusStreptococcus

SpeciesSpecies SerotySerotypepe

SourceSource

S. mutansS. mutans c,e,fc,e,f HumanHuman

S. sobrinusS. sobrinus d,g,hd,g,h HumanHuman

S. cricetusS. cricetus aa Sometimes human, mostly rats Sometimes human, mostly rats and hamstersand hamsters

S. rattusS. rattus bb Sometimes humans, mostly ratsSometimes humans, mostly rats

S. downeiS. downei hh Macaque monkeyMacaque monkey

S. macacaeS. macacae cc Macaque monkeyMacaque monkey

S. ferusS. ferus cc RatsRats

How does Strep mutansHow does Strep mutans

attatch to teeth and cause attatch to teeth and cause caries?caries?

Biofilm FormationBiofilm Formation

EnvironmentEnvironment

Require a non-shedding Require a non-shedding Needs nutritionally rich media for Needs nutritionally rich media for

growth.growth. Optimum temp for growth is 37° C, or Optimum temp for growth is 37° C, or

25-42°C.25-42°C. Low pH Low pH Transmission: Vertical and HorizontalTransmission: Vertical and Horizontal

TransmissionTransmission

VerticalVerticalParent to childParent to child

HorizontalHorizontalNon-parent Non-parent

same same species species transfertransfer

Role of mutacinRole of mutacin

Window of Window of infectivityinfectivity

S. mutans structuresS. mutans structures

AdhesinAdhesin A surface structure or macromolecule that A surface structure or macromolecule that

binds a bacterium to a specific surface.binds a bacterium to a specific surface. Antigen Antigen (Ag) I/II(Ag) I/II or or SpaPSpaP

Attatches to salivary pellicle receptors, Attatches to salivary pellicle receptors, salivary agglutinins, and other bacteria.salivary agglutinins, and other bacteria.

Also provides mechanism for binding of Also provides mechanism for binding of salivary agglutinin glycoprotein to the salivary agglutinin glycoprotein to the streptococcal cell surface-generates receptor streptococcal cell surface-generates receptor for other bacteria to adhere.for other bacteria to adhere.

Enables P. gingivalis to adhere to streptococci, Enables P. gingivalis to adhere to streptococci, enabling secondary colonizers to be enabling secondary colonizers to be incorporated into plaque communities.incorporated into plaque communities.

Extracellular enzymesExtracellular enzymes 1. Gtf-I1. Gtf-I

Forms insoluble glucans with mostly Forms insoluble glucans with mostly αα1,3 links 1,3 links between glucose polymers (mutans).between glucose polymers (mutans).

2. Gtf-S2. Gtf-S Forms water soluble glucans with mostly Forms water soluble glucans with mostly αα 1,6 1,6

links between glucose polymers (dextrans).links between glucose polymers (dextrans). 3. Gtf-SI3. Gtf-SI

Forms both water soluble and insoluble Forms both water soluble and insoluble glucans.glucans.

4. Ftf4. Ftf Forms water soluble fructose Forms water soluble fructose

GlucansGlucans

Tooth adherenceTooth adherence Promotes aggregation Promotes aggregation Biofilm accumulationBiofilm accumulation Retention of bacterial nutrientsRetention of bacterial nutrients Some antibodies prevent GTF Some antibodies prevent GTF

function and are protective.function and are protective.

DextranasesDextranases

Can convert glucan into glucose for Can convert glucan into glucose for glycolysis. glycolysis.

Break down Break down αα-1,6 linkages of -1,6 linkages of glucose into glucose into αα-1,3 linkages.-1,3 linkages.

Glucans can serve as attachment Glucans can serve as attachment mechanisms and energy stores.mechanisms and energy stores.

LTA LTA

Lipoteichoic acid is an amphipathic Lipoteichoic acid is an amphipathic constituent of the gram-positive constituent of the gram-positive bacteria outer-envelope.bacteria outer-envelope.

Can stimulate inflammation-TLR2Can stimulate inflammation-TLR2 Analgous to LPS in gram negative Analgous to LPS in gram negative

bacteria.bacteria. May help in adherenceMay help in adherence Key in virulence.Key in virulence. Area for possible vaccine?Area for possible vaccine?

Cell wallsCell walls

Vaccines AgainstVaccines Against

Dental CariesDental Caries

Effective VaccinesEffective Vaccines

Identify the bad guy.Identify the bad guy. Identify the best target to destroy Identify the best target to destroy

the bad guy.the bad guy. Identify the component of the Identify the component of the

immune system that should be immune system that should be targeted.targeted.

Vaccines: Whole or part?Vaccines: Whole or part? Early vaccinations involved patients Early vaccinations involved patients

swallowing boluses of killed S. mutans.swallowing boluses of killed S. mutans. This induced heart cross-reactive This induced heart cross-reactive

antibodies.antibodies. Cardiolipin (diphosphatidyl glycerol)Cardiolipin (diphosphatidyl glycerol)

May no longer be a concern?May no longer be a concern? Removed using a preadsorption techniqueRemoved using a preadsorption technique

More recent efforts have focused on More recent efforts have focused on protein expression and secretionprotein expression and secretion..





Should NOT harm the host!Should NOT harm the host!

Role of IgARole of IgA

Prevents colonizationPrevents colonization Key in vaccine developmentKey in vaccine development More IgA produced daily than any More IgA produced daily than any

other immunoglulin.other immunoglulin. Finding ways to prolong the Finding ways to prolong the

availability of antigens in the availability of antigens in the secretory IgA will improve dental secretory IgA will improve dental caries vaccinations.caries vaccinations.

VaccinesVaccines

Ag I/II vaccine would prevent binding.Ag I/II vaccine would prevent binding. Molecules that act as Molecules that act as adjuvantsadjuvants, such , such

as cholera toxin B and E coli. heat-as cholera toxin B and E coli. heat-liable toxin, improve the longevity of liable toxin, improve the longevity of the IgA response to antigens from S. the IgA response to antigens from S. mutans.mutans.

RecombinantRecombinant strains methods also strains methods also reduce cross-reactivity problems and reduce cross-reactivity problems and help prolong IgA response as well.help prolong IgA response as well.

Target AntigensTarget Antigens

Subunit vaccinationSubunit vaccination Bacerial antigensBacerial antigens

Synthetic peptidesSynthetic peptides ProteinsProteins Target GtfTarget Gtf

Enteric PathwayEnteric Pathway

Put antigens in a harmless enteric Put antigens in a harmless enteric bacteriabacteria

Natural proliferation in gut; greater Natural proliferation in gut; greater power than capsules with the antigenpower than capsules with the antigen

ConsiderationsConsiderations

Is the bug really harmelss?Is the bug really harmelss?

Plasmid vectors can encode Plasmid vectors can encode resistanceresistance

Active or Passive?Active or Passive?

Which is better?Which is better?

Active immunity will produce Active immunity will produce higher titer’s.higher titer’s.

Route?Route?

Oral and intranasal favored thus Oral and intranasal favored thus far.far.

Public considerationsPublic considerations

1950’s-4 vaccines; 1:10,000 autism1950’s-4 vaccines; 1:10,000 autism 1980’s-8 vaccines; 1/2,6001980’s-8 vaccines; 1/2,600 1990’s-10 vaccines; 1/3501990’s-10 vaccines; 1/350 Today-13 vaccines, given in 33 shots Today-13 vaccines, given in 33 shots

before a child is 2 years of agebefore a child is 2 years of age

1/100 boys, 1/400 girls1/100 boys, 1/400 girls

is diagnosed with autismis diagnosed with autism

ConsiderationsConsiderations

Debate similar to fluoride?Debate similar to fluoride?

How would one more vaccine be How would one more vaccine be received?received?

Thank You!Thank You!

The Microbiology of Dental Caries. Caries defined Dental caries- an infectious disease that damages...

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