Oral Keystone pathagens

Question 1

The quest to identify specific periodontal pathogens has led to significant progress,
including the identification of a number of candidates, mostly gram …………, ………..aerobic
bacteria that colonize subgingival tooth sites. Foremost amongst this group are three species
which comprise the so-called “………….”, are frequently isolated together, and are
strongly associated with diseased sites in the mouth:

Answer 1

The quest to identify specific periodontal pathogens has led to significant progress,
including the identification of a number of candidates, mostly gram-negative anaerobic
bacteria that colonize subgingival tooth sites. Foremost amongst this group are three species
which comprise the so-called “red complex”, are frequently isolated together, and are
strongly associated with diseased sites in the mouth: Porphyromonas gingivalis (formerly
known as Bacteroides gingivalis)20, Treponema denticola and Tannerella forsythia

Question 2

In this regard, the Argspecific
cysteine proteinases (gingipains) of P. gingivalis exhibit complement ……….
convertase-like activity, which generates high levels of …………. locally to activate the ………
receptor (…………) on leukocytes (Figure 1a). ………… signalling is involved in crosstalk with
…………………., which is activated in parallel by P. gingivalis surface ligands,
and the crosstalk leads to enhanced inflammation but impaired leukocyte killing
capacity2

Answer 2

In this regard, the Argspecific
cysteine proteinases (gingipains) of P. gingivalis exhibit complement C5
convertase-like activity, which generates high levels of C5a locally to activate the C5a
receptor (C5aR) on leukocytes (Figure 1a). C5aR signalling is involved in crosstalk with
Toll-like receptor 2 (TLR2), which is activated in parallel by P. gingivalis surface ligands,
and the crosstalk leads to enhanced inflammation but impaired leukocyte killing
capacity2

Question 3

P.gingivalis can also inhibit the synthesis of …… by epithelial cells to delay the recruitment of
………… and facilitate its initial colonization of the periodontium2

Answer 3

P.
gingivalis can also inhibit the synthesis of IL-8 by epithelial cells to delay the recruitment of
neutrophils and facilitate its initial colonization of the periodontium2

Question 4

The synthesis of ………
by the junctional gingival epithelium, adjacent to the tooth surface, is thought to be an
important feature of the healthy periodontium because it generates a gradient for recruitment
of ……….. into the gingival crevice.

Answer 4

The synthesis of IL-8
by the junctional gingival epithelium, adjacent to the tooth surface, is thought to be an
important feature of the healthy periodontium because it generates a gradient for recruitment
of neutrophils into the gingival crevice.

Question 5

The subversion of recruited leukocytes by wild-type P. gingivalis may allow uncontrolled
growth of other species in the same biofilm, consistent with the observed elevation of the
total microbiota count following P. gingivalis colonization of the murine periodontium25.
Moreover, uncontrolled bacterial growth leads to enhanced complement-dependent
destructive inflammation, which generates abundant tissue breakdown products (e.g.,
degraded proteins and hemin) that serve the nutritional needs of the bacteria (Figure 2). This
may fuel further changes to the biofilm and stabilize the transition to a disease-provoking
microbiota. The inflammatory environmental changes can be better exploited by proteolytic
and asaccharolytic bacteria, i.e., those organisms associated with periodontal disease rather
than health9

Answer 5

The subversion of recruited leukocytes by wild-type P. gingivalis may allow uncontrolled
growth of other species in the same biofilm, consistent with the observed elevation of the
total microbiota count following P. gingivalis colonization of the murine periodontium25.
Moreover, uncontrolled bacterial growth leads to enhanced complement-dependent
destructive inflammation, which generates abundant tissue breakdown products (e.g.,
degraded proteins and hemin) that serve the nutritional needs of the bacteria (Figure 2). This
may fuel further changes to the biofilm and stabilize the transition to a disease-provoking
microbiota. The inflammatory environmental changes can be better exploited by proteolytic
and asaccharolytic bacteria, i.e., those organisms associated with periodontal disease rather
than health9

Question 6

Importantly, specific removal of ……………. from the periodontal biofilm (by means of a C5aR
antagonist) reverses the dysbiotic changes25 (Figure 1a), suggesting that dysbiotic diseases
could be treated by specific targeting of keystone pathogens.

Answer 6

Importantly,
specific removal of P. gingivalis from the periodontal biofilm (by means of a C5aR
antagonist) reverses the dysbiotic changes25 (Figure 1a), suggesting that dysbiotic diseases
could be treated by specific targeting of keystone pathogens.