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Get the Key for Get the Key for Tomorrow’s Dentistry Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Danisco Cultor and Lotte Korea Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION KOREAN CARIES PREVENTION ASSOCIATION Seoul April 22, Seoul April 22, 2001 2001

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Page 1: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Get the Key for Get the Key for Tomorrow’s DentistryTomorrow’s Dentistry

Get the Key for Get the Key for Tomorrow’s DentistryTomorrow’s Dentistry

a symposium organized by the

Danisco Cultor and Lotte KoreaDanisco Cultor and Lotte Korea

and sponsored by

KOREAN CARIES PREVENTION ASSOCIATIONKOREAN CARIES PREVENTION ASSOCIATION

Seoul April 22, 2001Seoul April 22, 2001

Page 2: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

The Influence and Mechanismof Xylitol

on Mutans Streptococci

The Influence and Mechanismof Xylitol

on Mutans Streptococci

Luc Trahan, PhDLuc Trahan, PhDGGroupe de roupe de RRecherche en echerche en ÉÉcologie cologie BBuccaleuccale

Faculté de médecine dentaireFaculté de médecine dentaireUniversité LavalUniversité LavalQuébec, CanadaQuébec, Canada

Page 3: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Principal ProposedPrincipal ProposedMechanisms of Action of XylitolMechanisms of Action of Xylitol

Principal ProposedPrincipal ProposedMechanisms of Action of XylitolMechanisms of Action of Xylitol

Lack of acid production by plaque bacteriaLack of acid production by plaque bacteria Increased saliva secretion and salivary buffer capacityIncreased saliva secretion and salivary buffer capacity Inhibition of demineralization of sound enamelInhibition of demineralization of sound enamel Remineralization of decalcified sitesRemineralization of decalcified sites Inhibition of acid production by MS from dietary sugarsInhibition of acid production by MS from dietary sugars Inhibition of MS growthInhibition of MS growth Selection of a new less virulent MS populationSelection of a new less virulent MS population Reduction of the transmission / implantation of MsReduction of the transmission / implantation of Ms

Page 4: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Aim and ContentAim and ContentAim and ContentAim and Content

Aim: To survey and summarize the influence and Aim: To survey and summarize the influence and the mechanisms of action of xylitol on the mechanisms of action of xylitol on Mutans Streptococci Mutans Streptococci

Background information on the dental plaque ecosystem Background information on the dental plaque ecosystem and the utilisation of sugars by MSand the utilisation of sugars by MS

Details of the effects of xylitol on MSDetails of the effects of xylitol on MS Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Summary and take home messagesSummary and take home messages

Page 5: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

Page 6: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

The Caries Etiological Factors Constitute The Caries Etiological Factors Constitute a Fragile Ecosystema Fragile Ecosystem

The Caries Etiological Factors Constitute The Caries Etiological Factors Constitute a Fragile Ecosystema Fragile Ecosystem

Xylitol

Plaque Tooth

Sugar

CARIES

SalivaSaliva

Fluoride

MultipleFactors

Sealant

Antiseptics

Page 7: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Modification of the PlaqueModification of the Plaque Ecosystem by Sugar ConsumptionEcosystem by Sugar Consumption

Modification of the PlaqueModification of the Plaque Ecosystem by Sugar ConsumptionEcosystem by Sugar Consumption

S MS M

SUGARSSUGARS

ACIDSACIDS

ACIDSACIDS

SUGARSSUGARS(sucrose)(sucrose)

Page 8: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Ecological Plaque HypothesisEcological Plaque Hypothesisand Prevention of Cariesand Prevention of Caries

Ecological Plaque HypothesisEcological Plaque Hypothesisand Prevention of Cariesand Prevention of Caries

EnvironmentalEnvironmentalchangeschanges

EcologicalEcologicalshiftshift

FermentableFermentableSugarSugar

AcidAcid

NeutralNeutralpHpH

Low Low pHpH

S. oralisS. oralisS. sanguisS. sanguis

MSMSLactobacilliLactobacilli

RemineralizationRemineralization

DemineralizationDemineralization

Marsh, P., 1991

Page 9: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Dietary Sugars: Source of Energy and Dietary Sugars: Source of Energy and Carbon for the Growth of Plaque BacteriaCarbon for the Growth of Plaque Bacteria

Dietary Sugars: Source of Energy and Dietary Sugars: Source of Energy and Carbon for the Growth of Plaque BacteriaCarbon for the Growth of Plaque Bacteria

OD

(66

0 m

m)

0 4 8 12 24

0,02

0,030,040,05

0,20

0,300,400,50

0,01

0,10

1,00

Sugar could be: sucrose

glucose

lactose

mannitol

sorbitol

etc..

Xylitol

Time (hours)

Page 10: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Acidic End-products GenerationAcidic End-products Generationfrom Dietary Sugars by Plaque Bacteriafrom Dietary Sugars by Plaque Bacteria

Acidic End-products GenerationAcidic End-products Generationfrom Dietary Sugars by Plaque Bacteriafrom Dietary Sugars by Plaque Bacteria

4,0

5,0

6,0

7,0

0 10 20 30 40

Time (minutes)

pH

Demineralization

Remineralization

Sugars

Xylitol

Sorbitol

Critical pH

Page 11: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Xylitol: a Caries PreventiveXylitol: a Caries Preventive 5C- Sugar Alcohol 5C- Sugar Alcohol

Xylitol: a Caries PreventiveXylitol: a Caries Preventive 5C- Sugar Alcohol 5C- Sugar Alcohol

CH2OH H-C-OH HO-C-H H-C-OH CH2OH XYLITOL C5H12O5

CH2OH H-C-OH HO-C-H H-C-OH CH2OH XYLITOL C5H12O5

CH2OH H-C-OH HO-C-H H-C-OH H-C-OH CH2OH SORBITOL C6H14O6

CH2OH H-C-OH HO-C-H H-C-OH H-C-OH CH2OH SORBITOL C6H14O6

CH2OH C=O HO-C-H H-C-OH H-C-OH CH2OHFRUCTOSE C6H12O6

CH2OH C=O HO-C-H H-C-OH H-C-OH CH2OHFRUCTOSE C6H12O6A NATURAL 5 CARBON SUGARA NATURAL 5 CARBON SUGAR

ALCOHOL (PENTITOL)ALCOHOL (PENTITOL)

Page 12: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Dietary Sugar Utilization Dietary Sugar Utilization by Oral Streptococciby Oral Streptococci

Dietary Sugar Utilization Dietary Sugar Utilization by Oral Streptococciby Oral Streptococci

ADP

ATP

Sugar~P

Glucose~P

PEP

Pyruvate

Lactate

ADPATP

Lactic acid

Sugar ADPATP

SugarADP+PPiPolysaccharides

reserves

ATPGlucose

Glucan Fructan

Sugar

PTS

P

Sucrose

Fructose

++

E

Page 13: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

5-C alcohol(xylitol)

PTS

PERMEASE

± acidicend-products

Lactic acidAcetic acidEthanoletc...

5-C alcohol

5-C alcohol~P

2-Ketopentose

2-Keto pentose~P

Carbohydrate pathways

DH

Kinase

Epimerisation

Five-carbon Sugar Alcohols Utilization by Non-oral Bacteria

Five-carbon Sugar Alcohols Utilization by Non-oral Bacteria

ADPADP

ATPATP

Page 14: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

5-C alcohol(xylitol)

PTS

PERMEASE

± acidicend-products

Lactic acidAcetic acidEthanoletc...

5-C alcohol

5-C alcohol~P

2-Ketopentose

2-Keto pentose~P

Carbohydrate pathways

DH

Kinase

Epimerisation

Incapacity for Oral Bacteria to Incapacity for Oral Bacteria to Utilize 5-Carbon Sugar Alcohols 5-Carbon Sugar Alcohols

Incapacity for Oral Bacteria to Incapacity for Oral Bacteria to Utilize 5-Carbon Sugar Alcohols 5-Carbon Sugar Alcohols

ADP

ATP

Page 15: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Inducible Six-carbon Sugar Alcohols Utilization by

Mutans Streptococci

Inducible Six-carbon Sugar Alcohols Utilization by

Mutans Streptococci

ADP

ATP

Mannitol~PSorbitol~P

Glucose~P

PEP

Pyruvate

Lactate

ADPATP

Lactic acid

ADP+PPiPolysaccharides

reserves

ATP

Sorbitol

PTS mtl

Mannitol

PTS sor

Page 16: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

Page 17: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Growth Inhibition ofGrowth Inhibition ofS. mutans S. mutans Strains by XylitolStrains by Xylitol

Growth Inhibition ofGrowth Inhibition ofS. mutans S. mutans Strains by XylitolStrains by Xylitol

Strains % inhibition

ATCC 27352GS5-2IngbrittNTCC 1044967158E3 (fresh isolate)67.3 (fresh isolate)

8207685846833

Page 18: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of Xylitol on Acid Production Effect of Xylitol on Acid Production Rate by Resting Cells of Rate by Resting Cells of S. mutansS. mutans

Effect of Xylitol on Acid Production Effect of Xylitol on Acid Production Rate by Resting Cells of Rate by Resting Cells of S. mutansS. mutans

Vadeboncoeur, C., 1983M INUTES

0 10 20 30 40

µ m

ole

H+

/ 16

mg

c ell s

( dr y

wei

ght)

0

10

20

30

40

Strain % inhibitionR27352 XS27352 X

6715Ingbritt

0496838

from xylitolfrom xylitol

from glucosefrom glucose

+ xylitol+ xylitol

Page 19: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Definition of MS SensitivityDefinition of MS Sensitivity to Xylitol to Xylitol

Definition of MS SensitivityDefinition of MS Sensitivity to Xylitol to Xylitol

Xs wild type strains Xs wild type strains : xylitol-sensitivexylitol-sensitive

Strains that are inhibited by xylitolStrains that are inhibited by xylitol

Xr natural mutants Xr natural mutants : xylitol-resistantxylitol-resistant

Strains that are Strains that are notnot inhibited by xylitol inhibited by xylitol

None of these strains ferment xylitol and none produce acid from it.

Page 20: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of the Addition of Xylitol to Growing Effect of the Addition of Xylitol to Growing

XXSS and X and XRR S. mutansS. mutans

Effect of the Addition of Xylitol to Growing Effect of the Addition of Xylitol to Growing

XXSS and X and XRR S. mutansS. mutans

Trahan, L., 1985

XR (± xyl)

XS (+ H2O)

XS (+ xyl)

T im e ( h o u r s )

0 1 2 3 4 5 6

OD

(66

0 nm

)

0 , 2 0

0 , 3 0

0 , 4 0

0 , 5 0

0 , 6 0

0 , 7 0

0 , 1 0

14C

-xyl

i to

l acc

um

ula

ted

0

2 0

4 0

6 0

8 0

1 0 0

1 2 0

XR

XS

+ xylitol

Page 21: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

FRUCTOSEXYLITOLXYLITOL

FRUCTOSE-6~PXYLITOL~PXYLITOL~P IIC

Enzyme I

Enzyme I~P

HPr(His~P)

HPr

PEP

Pyruvate

IIB

~ IICIIA

P

~

P

IIB~IIA~

P P

FRUCTOSE

FRUCTOSE-1-~P

ConstitutiveConstitutivefructose-PTSfructose-PTS

InducibleInduciblefructose-PTSfructose-PTS

S. mutansS. mutans Constitutive Fructose-PTS Constitutive Fructose-PTS also Transports Xylitolalso Transports Xylitol

Benchabane, H., 1997

Page 22: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Xylitol Transport Xylitol Transport and Expulsion in and Expulsion in

S. mutansS. mutans

Xylitol Transport Xylitol Transport and Expulsion in and Expulsion in

S. mutansS. mutans

FRUCTOSE

PTS

PTS

Sugar

Xylitol

Sugar~P

PEP

Pyruvate

ADP

ATP

ADP

ATP

Xylitol~P

EXPULSION

Xylitol

PiLactate

Lacticacid

Trahan L. 1996

Page 23: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Establishment and Establishment and Consequences of a Consequences of a Xylitol Futile CycleXylitol Futile Cycle

Establishment and Establishment and Consequences of a Consequences of a Xylitol Futile CycleXylitol Futile Cycle

FRUCTOSE

PTS

PTS

Sugar

Sugar~P

PEP

Pyruvate

ADP

ATP

ADP

ATP

Xylitol~P

EXPULSION

Xylitol

PiLactateE Lactic

acid

Xylitol

Page 24: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

PTS

Sugar

Sugar~P

PEP

Pyruvate

ADP

ATP

ADP

ATP

Lactate

FRUCTOSE

PTS

Xylitol

Lacticacid

Absence of Constitutive Absence of Constitutive Fructose PTS Activity Fructose PTS Activity

in Xr Mutantsin Xr Mutants

Absence of Constitutive Absence of Constitutive Fructose PTS Activity Fructose PTS Activity

in Xr Mutantsin Xr Mutants

Page 25: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of Xylitol andEffect of Xylitol and Xylitol-5-phosphate on Selected Xylitol-5-phosphate on Selected

Glycolytic Enzymes Glycolytic Enzymes in Vitroin Vitro

Effect of Xylitol andEffect of Xylitol and Xylitol-5-phosphate on Selected Xylitol-5-phosphate on Selected

Glycolytic Enzymes Glycolytic Enzymes in Vitroin Vitro

EnzymeEnzyme% % inhibition byinhibition by

xylitolxylitol xylitol 5-Pxylitol 5-P

PGIPGI 00 >90>906-6-PFKPFK 00 50501-1-PFKPFK 00 1010PKPK 00 >90>90LDH 0 0

Page 26: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Proposed Model of the Effect Proposed Model of the Effect of Xylitol on of Xylitol on S. mutansS. mutans

Glucose-6-P

Fructose-6-P

Fructose-1,6-di-P

GA3P

1,3-DPG

DHAP

2-PG

PEP Pyruvate Lactate

Xylitol-P

GlucosePGI

6-PFK

PK LDH

Xylitol

3-PG

-

-

+

Xylitol

Glucose

PTSman

PTSfru

PMF

Glycogen

Lacticacid

Trahan L., 1996

Page 27: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

Page 28: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

In vitro In vitro Selection of XSelection of XRR Natural Mutants Natural Mutants Following Growth in the Presence of Following Growth in the Presence of XylitolXylitol

In vitro In vitro Selection of XSelection of XRR Natural Mutants Natural Mutants Following Growth in the Presence of Following Growth in the Presence of XylitolXylitol

XYLITOLXYLITOLXYLITOLXYLITOL XYLITOLXYLITOLXYLITOLXYLITOL

Page 29: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

In vivo In vivo Selection of XSelection of XRR Natural Mutants in Natural Mutants in Saliva and Plaque of Xylitol ConsumersSaliva and Plaque of Xylitol ConsumersIn vivo In vivo Selection of XSelection of XRR Natural Mutants in Natural Mutants in Saliva and Plaque of Xylitol ConsumersSaliva and Plaque of Xylitol Consumers

XYLITOLXYLITOL XYLITOLXYLITOL

Page 30: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Proportion of salivary natural XProportion of salivary natural XRR

MS strains in patientsMS strains in patientsProportion of salivary natural XProportion of salivary natural XRR

MS strains in patientsMS strains in patients

PatientsPatientsNumber of strainsNumber of strains

% % XXRRTotalTotal XXRR XXSS

ControlsControls 2020 22 1818 1010

Xylitol-consumersXylitol-consumers 5454 4747 77 8787

Page 31: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Occurrence in 1988 of XOccurrence in 1988 of XRR Salivary Salivary Strains in Patients from the Strains in Patients from the

Ylivieska Xylitol Study (1982-1984)Ylivieska Xylitol Study (1982-1984)

Occurrence in 1988 of XOccurrence in 1988 of XRR Salivary Salivary Strains in Patients from the Strains in Patients from the

Ylivieska Xylitol Study (1982-1984)Ylivieska Xylitol Study (1982-1984)

GroupGroup % % XXRR

ControlsControls 35.0 ± 6.435.0 ± 6.4Active consumersActive consumers 82.5 ± 5.782.5 ± 5.7Former consumersFormer consumers

NN

161614141313 74.6 ± 8.674.6 ± 8.6

Page 32: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of Xylitol Consumption Effect of Xylitol Consumption on the Plaque Ecosystemon the Plaque Ecosystem

Effect of Xylitol Consumption Effect of Xylitol Consumption on the Plaque Ecosystemon the Plaque Ecosystem

S M S M

XYLITOLXYLITOL

Page 33: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

Page 34: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of a Heat or Xylitol Stress onEffect of a Heat or Xylitol Stress on 1414C-labelled Protein Profile of C-labelled Protein Profile of S. mutansS. mutans

Effect of a Heat or Xylitol Stress onEffect of a Heat or Xylitol Stress on 1414C-labelled Protein Profile of C-labelled Protein Profile of S. mutansS. mutans

Page 35: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Densitometric Analysis of Protein Profiles of Densitometric Analysis of Protein Profiles of Xr and Xs MS Strains After a Xylitol ExposureXr and Xs MS Strains After a Xylitol ExposureDensitometric Analysis of Protein Profiles of Densitometric Analysis of Protein Profiles of

Xr and Xs MS Strains After a Xylitol ExposureXr and Xs MS Strains After a Xylitol Exposure

Xs strainXs strain Xr strainXr strainProtein IDProtein ID

ControlControl XylitolXylitolexposureexposure

ControlControl XylitolXylitolexposureexposure

HSP-70HSP-70 1.001.00 1.081.081.001.000.530.53HSP-60HSP-60 1.001.00 0.820.821.001.000.540.54

40 40 kDakDa 1.001.00 1.001.00 1.091.091.531.53

71 71 kDakDa 1.001.00 1.161.161.001.000.580.5863 63 kDakDa 1.001.00 1.111.111.001.000.570.5757 57 kDakDa 1.001.00 1.031.031.001.001.371.3753 53 kDakDa 1.001.00 0.950.951.001.000.530.5350 50 kDakDa 1.001.00 0.950.951.001.001.481.48

Page 36: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Effect of a Xylitol Shock on the Survival Effect of a Xylitol Shock on the Survival Capacity of Capacity of S. mutansS. mutans 123.1 123.1

Effect of a Xylitol Shock on the Survival Effect of a Xylitol Shock on the Survival Capacity of Capacity of S. mutansS. mutans 123.1 123.1

Number of surviving cells (CFU /mL)Number of surviving cells (CFU /mL)

S. mutans S. mutans 123.1 X123.1 XSS S. mutans S. mutans 123.1 X123.1 XRR

ControlControl XylitolXylitol X/C X/C ControlControl XylitolXylitol X/CX/C

3.51±0.13 x103.51±0.13 x1010 10 1.51±0.47 x101.51±0.47 x1010 10 0.430.43 11 22 .62±0.68 x10.62±0.68 x109 9 2.78±0.38 x102.78±0.38 x1099 1.061.06 44

1.45±0.38 x101.45±0.38 x1099 0.654±0.09 x10 0.654±0.09 x1099 0.450.45 22 8.15±0.34 x10 8.15±0.34 x108 8 8.44±0.42 x108.44±0.42 x1088 1.031.03 55

3.07±0.60 x103.07±0.60 x1099 2.19±0.05 x10 2.19±0.05 x1099 0.710.71 33 1.60±0.39 x10 1.60±0.39 x109 9 1.91±0.43 x101.91±0.43 x1099 1.191.19 66

1, 2, 3 p<0.00031, 2, 3 p<0.0003 4, 5, 6 p>0.114, 5, 6 p>0.11

Page 37: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

Page 38: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

Preliminary Results on the Attenuated Preliminary Results on the Attenuated Virulence Properties of XVirulence Properties of XRR MS Strains MS Strains

Selected by Xylitol ...Selected by Xylitol ...

Preliminary Results on the Attenuated Preliminary Results on the Attenuated Virulence Properties of XVirulence Properties of XRR MS Strains MS Strains

Selected by Xylitol ...Selected by Xylitol ...

a reduced acid production from sugarsa reduced acid production from sugars a modified extracellular polysaccharides synthesisa modified extracellular polysaccharides synthesis a modified bacterial agglutination/aggregation capacitya modified bacterial agglutination/aggregation capacity an elevated glucan-binding protein C elevated 20 foldsan elevated glucan-binding protein C elevated 20 folds

When XWhen XRR strains are compared with corresponding X strains are compared with corresponding XSS strains the accumulated evidence suggest:strains the accumulated evidence suggest:

Page 39: Get the Key for Tomorrow’s Dentistry a symposium organized by the Danisco Cultor and Lotte Korea and sponsored by KOREAN CARIES PREVENTION ASSOCIATION

an increased dextran-dependent aggregation capacityan increased dextran-dependent aggregation capacity a reduced adherence to saliva coated hydroxyapatite a reduced adherence to saliva coated hydroxyapatite

and glass surfacesand glass surfaces a reduced cariogenicity in a rat modela reduced cariogenicity in a rat model an absence of DnaK and GroEL stress proteins an absence of DnaK and GroEL stress proteins

response to a xylitol exposureresponse to a xylitol exposure a larger bacterial cells shedding from plaque to salivaa larger bacterial cells shedding from plaque to saliva

Preliminary Results on the Attenuated Preliminary Results on the Attenuated Virulence Properties of XVirulence Properties of XRR MS Strains MS Strains

Selected by XylitolSelected by Xylitol

Preliminary Results on the Attenuated Preliminary Results on the Attenuated Virulence Properties of XVirulence Properties of XRR MS Strains MS Strains

Selected by XylitolSelected by Xylitol

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ContentContentContentContent Background information on the dental plaque Background information on the dental plaque

ecosystem and the utilisation of sugars by MSecosystem and the utilisation of sugars by MS Details of the effects of xylitol on MSDetails of the effects of xylitol on MS

Inhibition of growth and acid production from sugarsInhibition of growth and acid production from sugars Selection of a new MS populationSelection of a new MS population

Recent progresses on the mechanisms of actionRecent progresses on the mechanisms of action Disturbed protein synthesis and reduced survivalDisturbed protein synthesis and reduced survival Virulence propertiesVirulence properties

Summary and take home messagesSummary and take home messages

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Summary of the Effects of Xylitol on Summary of the Effects of Xylitol on Mutans Streptococci ...Mutans Streptococci ...

Summary of the Effects of Xylitol on Summary of the Effects of Xylitol on Mutans Streptococci ...Mutans Streptococci ...

A variable intensity inhibition of growth on most A variable intensity inhibition of growth on most fermentable sugars resulting from: fermentable sugars resulting from:

the establishment of an energy spending futile cyclethe establishment of an energy spending futile cycle

the strong inhibition of glycolytic pathway enzymesthe strong inhibition of glycolytic pathway enzymes

An inhibition of acid production from dietary sugars An inhibition of acid production from dietary sugars also resulting from the above mentioned mechanismsalso resulting from the above mentioned mechanisms

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Summary of the Summary of the EffectsEffects of Xylitol on of Xylitol on Mutans StreptococciMutans Streptococci

Summary of the Summary of the EffectsEffects of Xylitol on of Xylitol on Mutans StreptococciMutans Streptococci

A selection of XA selection of XRR MS strains with apparently less MS strains with apparently less virulent propertiesvirulent properties

A disturbance of protein synthesis, including stress A disturbance of protein synthesis, including stress proteins DnaK and GroEL, resulting in a reduced proteins DnaK and GroEL, resulting in a reduced capacity to survive further exposure to xylitolcapacity to survive further exposure to xylitol

A reduced capacity to be transmitted from mother to A reduced capacity to be transmitted from mother to childchild

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Clinical Benefits for Patients Clinical Benefits for Patients Chewing Xylitol GumChewing Xylitol Gum

Clinical Benefits for Patients Clinical Benefits for Patients Chewing Xylitol GumChewing Xylitol Gum

a reduced caries incidence via:a reduced caries incidence via: an increased saliva secretion and salivary buffer capacityan increased saliva secretion and salivary buffer capacity an inhibition of demineralization of sound enamelan inhibition of demineralization of sound enamel a remineralization of decalcified sitesa remineralization of decalcified sites an inhibition of acid production from dietary sugarsan inhibition of acid production from dietary sugars

a less acidogenic and less aciduric plaque ecosystema less acidogenic and less aciduric plaque ecosystem

The accumulated evidence suggestsThe accumulated evidence suggests::

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Additional Clinical Benefits from the Additional Clinical Benefits from the Inhibitory Action of Xylitol on MSInhibitory Action of Xylitol on MS

Additional Clinical Benefits from the Additional Clinical Benefits from the Inhibitory Action of Xylitol on MSInhibitory Action of Xylitol on MS

a reduction of:a reduction of: plaque indicesplaque indices the amount of plaque accumulatedthe amount of plaque accumulated the number of MS in plaque and salivathe number of MS in plaque and saliva the capacity to transmit MS strainsthe capacity to transmit MS strains

a selection of Xr MS strains with:a selection of Xr MS strains with: apparently less virulent propertiesapparently less virulent properties a loss of MS strains from plaque to salivaa loss of MS strains from plaque to saliva

The accumulated evidence suggests:The accumulated evidence suggests:

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Take Home Message # 1Take Home Message # 1Take Home Message # 1Take Home Message # 1

Xylitol influences positively the plaque microflora in Xylitol influences positively the plaque microflora in establishing ecological conditions less appropriate for establishing ecological conditions less appropriate for the low-pH bacteria producing acidic end-products the low-pH bacteria producing acidic end-products and thus beneficial for the patientsand thus beneficial for the patients

Long and/or frequent exposure to xylitol does not Long and/or frequent exposure to xylitol does not result, for oral bacteria, in adaptation to metabolize result, for oral bacteria, in adaptation to metabolize the sugar-alcoholthe sugar-alcohol

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Take Home Message # 2Take Home Message # 2Take Home Message # 2Take Home Message # 2

Xylitol is not only unfermentable by oral bacteria but Xylitol is not only unfermentable by oral bacteria but it also inhibits most mutans streptococciit also inhibits most mutans streptococci

Biochemical mechanisms explaining the inhibition of Biochemical mechanisms explaining the inhibition of the growth of, and acid production by, mutans the growth of, and acid production by, mutans streptococci have been well known for a few yearsstreptococci have been well known for a few years

Knowledge on other mechanisms involving disturbed Knowledge on other mechanisms involving disturbed proteins synthesis by xylitol and reduced survival of proteins synthesis by xylitol and reduced survival of MS to repeated exposures to xylitol is progressingMS to repeated exposures to xylitol is progressing

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Take Home Message # 3Take Home Message # 3Take Home Message # 3Take Home Message # 3

The occurrence of xylitol-resistant strains in xylitol The occurrence of xylitol-resistant strains in xylitol consumers is explained by a simple selection of consumers is explained by a simple selection of natural mutantsnatural mutants

Xylitol-resistance of MS does not impair its use in Xylitol-resistance of MS does not impair its use in caries prevention and is most probably beneficial for caries prevention and is most probably beneficial for the patientsthe patients

Knowledge of the hypothesized less virulent Knowledge of the hypothesized less virulent properties of xylitol-resistant strains is progressingproperties of xylitol-resistant strains is progressing

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This presentation is the result of various This presentation is the result of various studies conducted with numerous studies conducted with numerous

graduate students and colleagues from graduate students and colleagues from Québec and FinlandQuébec and Finland

This presentation is the result of various This presentation is the result of various studies conducted with numerous studies conducted with numerous

graduate students and colleagues from graduate students and colleagues from Québec and FinlandQuébec and Finland

THANK YOUTHANK YOU

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A campus with more A campus with more than 35 000 studentsthan 35 000 students

A Faculté de médecine A Faculté de médecine dentaire since 1969dentaire since 1969

A french speaking university founded in 1683A french speaking university founded in 1683 A french speaking university founded in 1683A french speaking university founded in 1683