Periodontal Disease

Bahan: Periodontal Disease. Dental Conference – MID.

November 11, 2004.
 Destructive Periodontal Disease

Absence of
Active Susceptible Presence of
Beneficial
Disease Host Pathogens
Species

-- From Socransky et al. (1992)

 Dental plaque biofilm infection
 Ecological point of view
 Ecological community evolved for survival as a whole
 Complex community of more than 400 bacterial species
 Dynamic equilibrium between bacteria and a
host defense
 Adopted survival strategies favoring growth in plaque
 “Selection” of “pathogenic” bacteria among microbial community
 Selection pressure coupled to environmental changes

 Disturbed equilibrium leading to pathology

 Opportunistic infection
 Dental Plaque Hypothesis`

 Specific plaque hypothesis

 Non-specific plaque hypothesis
 Intermediate or ecological plaque hypothesis
 Qualitatively distinct bacterial composition:
healthy vs. disease (subjects, sites)
 Pathogenic shift; disturbed equilibrium
 A small group of bacteria: Gram (-), anaerobic
Specific
plaque
hypothesis

The specific plaque hypothesis is a concept that

describes how periodontal disease can be attributed to
individually identifiable bacterial species.
Non-Specific
plaque
hypothesis

The accumulation of plaque on the tooth surfaces is the

sole cause of periodontal disease.
Ecological
plaque
hypothesis

The carious disease can be attributed to changes in the

environment which disrupt homeostasis between the
plaque microflora and host
 Perubahan pH plaque pada individu (A) sering
mengkonsumsi fermentable carbohydrate, (B) membatasi
masukan karbohidrat sehari-hari
Gambaran kisaran pH untuk pertumbuhan beberapa mikroba
Health vs. disease microflora in dental plaque

Potential pathogens
 100 Years of Periodontal Microbiology
1890 Fusoformis fusiformis (1890)
Specific Streptococci (1906)
Spirochetes (1912)
Amoeba (1915)

1930
Mixed Infection - Fusospirochetal (1930)
Non-specific Mixed Infection - with Black pigmented
Bacteroides (1955)

Spirochete - ANUG (1965)

1970 A. viscosus (1969)

A. actinomycetemcomitans (1976)
Specific P. gingivalis (1980)
P. intermedia (1980)
C. rectus
1990 B. forsythus
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Broadly categorized into gingivitis and periodontitis

Clinical features of plaque-related gingivitis are

redness, edema and bleeding

Periodontitis usually develops from a pre-existing

gingivitis

Not every gingivitis leads to periodontitis

Acute necrotizing ulcerative
gingivitis
 MICROBIOLOGY OF PERIODONTAL
DISEASE
• Periodontitis can be classified into two main groups:

• Chronic (the most prevalent form)

• Aggressive
Localized and generalized
Rapidly progressive
Prepubertal
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Initial lesion: Plaque at junctional epithelium,

increased flow of GCV, migration of neutrophils
due to acute inflammation. Mostly Gram + cocci

Early lesion: Gingival infiltrate dominated by

lymphocytes (75%) and macrophages, with some
plasma cells at the periphery. Actinomyces,
spirochetes and capnophilic organisms
MICROBIOLOGY OF PERIODONTAL
DISEASE
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Established lesion: Predominance of plasma cells

and B lymphocytes. P. gingivalis and Prevotella
intermedia

Advanced lesion: Activated complement and

osteoclast activating factor (secreted by T
lymphocytes) stimulate bone resorption
Gross periodontal
disease
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Microorganisms in:

Healthy gingival sulcus:

Gram-positive and facultative anaerobic organisms

Chronic periodontitis:
~75% Gram-negative (90% strict anaerobes)
Motile rods and spirochetes
Predominant plaque bacterial morphotypes in
health, gingivitis and periodontitis
Microbiota Associated with Periodontal health,
Gingivitis, and Advanced periodontal disease

100% Gram-negative rods

80% Gram-positive rods

60%
Gram-negative
cocci
40%
Gram-positive cocci
20%

0%
Healthy - Gingivitis
supragingival crevicluar
Gingivitis

Predominant cocci and simple rods

Periodontitis

Predominant filamentous

Gram (-), anaerobic rods

Microbial complexes in biofilms

 Not randomly exist, rather as specific

associations among bacterial species
 Socransky et al. (1998) examined over 13,000
subgingival plaque samples from 185 adults, and
identified six specific microbial groups of
bacterial species
 Subgingival Microbial Complex
Actinomyces
species
V. parvula P. gingivalis
A. odontolyticus B. forsythus
S. mitus T. denticola
S. oralis
S. sanguis C. rectus
Streptococcus sp.
S. gordonii C. gracilis P. intermedia
S. intermedius P. nigrescens E. nodatum
P. micros
F. nuc. nucleatum
S. constellatus
F. nuc. vincentil
E. corrodens F. nuc. polymorphum
C. gingivalis F. periodonticum
C. sputigena
C. ochracea
C. concisus C. showae
A. actino. a A. antino. b
S. noxia
 MICROBIOLOGY OF PERIODONTAL
DISEASE

The presence of putative periodontopathogens

can be detected by:
• Microscopy
• Microbial cultures
• Enzymes liberated by the organisms
• DNA/RNA probes
Criteria for defining putative
periodontal pathogens

 Association with disease

 Elimination should result in clinical
improvement
 Host response to pathogens
 Virulence factors
 Animal studies demonstrating tissue destruction
Possible Etiologic Agents of Periodontal Disease

 Actinobacillus actinomycetemcomitans
 Porphyromonas gingivalis
 Tannerella forsythia (Bacteroides forsythus)
 Prevotella intermedia
 Spirochetes
 Fusobacterium nucleatum
 Eikenella corrodens
 Campylobacter rectus (Wolinella recta)
 Peptostreptococcus micros
 Streptococcus intermedius
Periodontal disease as an infectious disease

 Events in all infectious disease:

 Encounter
 Entry
 Spread
 Multiplication
 Damage
 Outcome
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Currently recognized key Gram-negative
periodontopathogens include:

Porphyromonas gingivalis
Prevotella intermedia
Bacteroides forsythus
Actinobacillus actinomycetemcomitans
Fusobacterium nucleatum
Capnocytophaga species
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Disease activity in periodontal disease ranges from

Slow, chronic, progressive destruction

Brief and acute “episodic bursts” with varying

intensity and duration
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Localized or generalized aggressive periodontitis

is strongly associated with Actinobacillus
actinomycetemcomitans, either alone or
synergistically with
Capnocytophaga species and
Porphyromonas gingivalis
 MICROBIOLOGY OF PERIODONTAL
DISEASE

Necrotizing ulcerative gingivitis is a specific,

anaerobic, polymicrobial infection due to the
combined activity of fusobacteria
(Fusobacterium nucleatum), and oral spirochetes
(Treponema spp.)

“Fusospirochaetal complex”
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Porphyromonas gingivalis

• Gram-negative rods, non-motile, obligatory anaerobes

• Growth requirements: Anaerobic conditions,
hemin (which carries iron and protoporphyrin)
& vitamin K
• Virulence factors: Capsular polysaccharides,
collagenase, trypsin-like proteases (gingipain),
keratinase, hemolysins, fibrinolysins,
hyaluronidase and phospholipase
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Actinobacillus actinomycetemcomitans

• Gram-negative coccobacilli, facultative anaerobic

• Colonizes buccal mucosa & plaque
• Virulence factors
Leukotoxin kills human neutrophils (-> release of
lysosomal enzymes) & macrophages
Immunosuppressive factor inhibits B-cell growth
LPS activates the alternate complement pathway
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Prevotella intermedia

• Gram-negative, pleomorphic rods, strict anaerobes

• Require vitamin K & hemin for growth
• Associated with chronic periodontitis &
dentoalveolar abscess
• Virulence factors
Phospholipase A, IgA/IgG proteases, mercaptans,
hydrogen sulfide
 MICROBIOLOGY OF PERIODONTAL
DISEASE
Spirochetes

• Long, thin, corkscrew-like, Gram-negative, anaerobic,

highly mobile bacteria
• Killed by oxygen, difficult to grow in media
• Virulence factors
Endotoxin
Ability to penetrate tissue
A factor that inhibits lymphocyte activation
Block fusion of phagosomes with lysosomes
Virulence factors

 Gene products that enhance a

microorganism’s potential to cause disease
 Involved in all steps of pathogenicity
 Attach to or enter host tissue
 Evade host responses
 Proliferate
 Damage the host
 Transmit itself to new hosts

 Define “the pathogenic personality”

 Virulence genes
Expression of virulence factors

 Constitutive
 Under specific environmental signals
 Can be identified by mimicking environmental signals
in the laboratory
 Many virulence-associated genes are coordinately
regulated by environmental signals
 Only in vivo
 Cannot be identified in the laboratory
 Anthrax toxin, cholera toxin
Identifying virulence factors

 Microbiological and biochemical studies

 In vitro isolation and characterization
 In vivo systems

 Genetic studies
 Study of genes involved in virulence
 Genetic transmission system

 Recombinant DNA technology

 Isogenic mutants
 Molecular form of Koch’s postulates (Falkow)
Virulence factors of A.
actinomycemtemcomitans
 Leukotoxin (RTX)
 Induce apoptosis
 Cytolethal distending toxin (CDT)
 Chaperonin 60
 LPS
 Apoptosis, bone resorption, etc
 OMP, vesicles
 Fimbriae
 Actinobacillin
 Collagenase
 Immunosuppressive factor
Virulence factors of P. gingivalis
 Involved in colonization and attachment
 Fimbriae, hemagglutinins, OMPs, and vesicles
 Involved in evading (modulating) host responses
 Igand complement proteases, LPS, capsule, other
antiphagocytic products
 Involved in multiplying
 Proteinases, hemolysins
 Involved in damaging host tissues and spreading
 Proteinases (Arg-, Lys-gingipains), Collagenase, trypsin-like
activity, fibrinolytic , keratinolytic, and other hydrolytic activities