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.
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.
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?
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.
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.
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?
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
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?
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..
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.
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.
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?