PRESENTED BY : Dr Krishna Das, PG Student

Periodontal disease is a significant global public health

concern and is probably the most common chronic infectious
disease of humans.

The importance of bacteria in dental plaque and its key role in
the causation of periodontal disease is well established.

It is clear that some organisms, such as P. gingivalis, A.
actinomycetemcomitans, spirochetes, and P. intermedia, are
strongly associated with a number of periodontal diseases.
However, periodontal disease never occurs in the absence of
a complex microbiota and it is often difficult , if not
impossible, to determine precisely how different organisms
contribute to an individual case of disease.
NON-SPECIFIC PLAQUE HYPOTHESIS

SPECIFIC PLAQUE HYPOTHESIS

ECOLOGIC PLAQUE HYPOTHESIS
Difficulties exist in the application of Koch's postulates to case of
periodontitis, three primary problems are:

(1) the inability to culture all the organisms that have been
associated with disease (e.g., many of the oral spirochetes)
(2) the difficulties inherent in defining and culturing sites of active
disease, and
(3) the lack of a good animal model system for the study of
periodontitis

In fact, if the ecologic plaque hypothesis proves correct, it must be
inherently impossible to fulfill Koch's postulates, since no single
organism or group of organisms is responsible for all cases of
disease.


According to these criteria, a potential pathogen must do the
following:
Be associated with disease, as evident by increases in the number
of organisms at diseased sites.
Be eliminated or decreased in sites that demonstrate clinical
resolution of disease with treatment
Induce a host response, in the form of an alteration in the host
cellular or humoral immune response
Be capable of causing disease in experimental animal models
Produce demonstrable virulence factors responsible for enabling the
microorganism to cause destruction of the periodontal tissues.

Aggregatibacter actinomycetemcomitans(Aa)
Porphyromonas gingivalis(Pg)
Tannerella forsythia (Bacteroides forsythus)(Tf)
Prevotella intermedia(Pi)
Spirochetes
Fusobacterium nucleatum(Fn)
Eikenella corrodens(Ec)
Campylobacter rectus (Wolinella recta)(Cr)
Peptostreptococcus micros(Pm)
Streptococcus intermedius(Si)

Targeting one or more pathogens will not necessarily cure disease,
since other organisms with similar activities might take their place.

It may make sense therefore to focus on the specific molecules that
contribute to disease (virulence factors), rather than on the
microorganisms that produce them.

The properties of a microorganism that enable it to cause disease are
referred to as virulence factors

In fact , it is often difficult to separate the virulence determinants from
the organisms that produce them.

For example, adhesins are produced by commensal organisms, as well as
by pathogens, yet only those adhesins that promote attachment of a
pathogenic organism could be considered virulence determinants.
With this in mind, some of the known or putative
virulence factors for periodontal disease are described
below. It is important to note the following:

1. Only a proportion of periodontal bacteria have ever
been isolated, and there are almost certainly many
other virulence factors that are currently unknown .

2. Most of our understanding of virulence factors has
come from studies on a very limited number of
bacterial species and strains. It is far from clear that
the molecules that have been studied in the greatest
detail are truly representative of their classes.

1. Factors that promote colonization
(adhesion & invasion)
2. Mechanisms that protect pathogenic
bacteria from the host
3. Microbial Mechanisms of Host Tissue
Damage
Bacterial species that colonize gingival sulcus and periodontal
pocket in this region must attach to available surfaces to avoid
displacement by the gingival crevicular fluid flow. Therefore,
adherence represents a virulence factor for periodontal
pathogens.

The initial colonizers the periodontal environment most likely
attach to the pellicle-or saliva-coated tooth surface. Eg.
adherence of Actinomyces viscosus and Porphyromonas
gingivalis through FIMBRIAE on the bacterial surface to proline-
rich proteins found on saliva-coated tooth surfaces.

Through its fimbriae, P. gingivalis also binds to epithelial cells
and fibroblasts.

Bacterial attachment to pre-existing plaque :
COAGGREGATION eg: adherence of A. viscosus (fimbriae) to
Streptococcus sanguis (polysaccharide receptor)

Bacterial adherence to host tissues likely plays a role in
colonization and may be a critical step in the process of
bacterial invasion.

Thus the ability of P. gingivalis to attach to other bacteria,
epithelial cells, and the connective tissue components
fibrinogen and fibronectin are all likely to be important in the
virulence of this microorganism.
It has been demonstrated that bacteria is present in periodontal tissues
in : Gingivitis
Necrotizing ulcerative gingivitis (NUG)
Aggressive Periodontitis (both localized and generalized)

Both gram-positive and gram-negative bacteria, including cocci, rods,
filaments, and spirochetes, have been observed in gingival connective
tissue and in proximity to alveolar bone.

Bacteria may enter host tissues through
-ulcerations in the epithelium of the gingival sulcus or pocket.
-direct penetration of bacteria into host epithelial or connective
tissue cells. eg, Aa, Pg, Fn & Td invade host tissue cells directly.

The clinical significance of bacterial invasion is not clear.

Bacterial species that have been identified as capable of
tissue invasion are strongly associated with disease & has
been proposed as a key factor that distinguishes pathogenic
from non-pathogenic bacteria.

Localization of bacteria to the tissues provides an ideal
position from which the organism can effectively deliver
toxic molecules and enzymes to the host tissue cells, and this
may be the significance of invasion as a virulence factor.
It has been speculated that the bursts of
disease activity observed in periodontitis
may be related to phases of bacterial invasion
of the tissues.

Provide a reservoir for recolonization which
indicates the use of systemic antibiotics in
combination with surgical therapy to
eliminate Aa from lesions with localized
aggressive periodontitis (LAP).

To survive in the periodontal environment, bacteria
must neutralize or evade the host mechanisms
involved in bacterial clearance and killing.

Bacterial adherence (allows bacteria to avoid
displacement by host secretions) and invasion
(disrupts the natural barriers formed by host tissue
cells) are representative strategies by which
microorganisms accomplish this task.

Periodontal bacteria neutralize or evade host
defenses through numerous other mechanisms.
For example,
-Immunoglobulins

immunoglobulin-degrading proteases

opsonization of bacteria
specific microorganisms

restricting bacterial adhesion
produce substances

phagocytosis

suppress the activity of or kill PMNs and lymphocytes


- Aa of two toxins (a leukotoxin and cytolethal distending toxin) that may be
important in the virulence of this microorganism in aggressive
periodontitis and possibly in chronic periodontitis.

- Similarly, Tf & Fn have been shown to induce apoptosis in lymphocytes.
(-)
Microorgamisms
Directly in degradation
of host tissue
Indirectly by release of biologic mediators
from host tissue cells
Some bacterial products inhibit the
growth or alter the metabolism of
host tissue cells; these include a
number of metabolic byproducts
such as ammonia; volatile sulfur
compounds; and fatty acids,
peptides, and indoles.
enzymes produced by periodontal
microorganisms eg. trypsinlike
enzymes,
induction of host tissue proteinases such
as elastase and matrix metalloproteinases
(MMPs)
Release of IL-1, TNF and prostaglandins from
monocytes, macrophages, and PMNs exposed
to bacterial endotoxin (lipopolysaccharide).
have the potential to stimulate bone
resorption and activate or inhibit other host
immune cells.
Periodontal pathogens or their pathogenic products must be able to
pass through the epithelial cell barrier in order to reach and cause
destruction to underlying tissues (the gingiva, cementum,
periodontal ligament and alveolar bone).

Once the organisms are firmly established in the gingiva, the host
responds to the bacterial onslaught, especially to the bacterial
lipopolysaccharide, by a marked and continual inflammatory
response, which results in the destruction of the periodontal tissues.

Periodontal pathogens possesses so many virulence factors but
unfortunate that only a few have been extensively studied. If we hope
to understand and eradicate this pathogen, it is critical that in-depth
investigations into the biochemistry, genetic expression, regulation
and mechanisms of action of these factors be initiated.