DETERMINANTS OF PATHOGENICITY- BASICS

1. DETERMINANTS OF BACTERIAL
PATHOGENICITY

2. PATHOGENICITY
• Pathogenicity is the ability to cause disease
Virulence
Degree of pathogenicity
10 bacteria of strain A > 1000 bacteria of strain B

3. VIRULENCE DETERMINANTS
• Called as virulence determinants or aggressins
• Possession of a single aggressin is never
sufficient for producing pathogenesis
• Aggressins vary among serotypes of bacteria

4. HOW VIRULENCE
DETERMINANTS
ARE STUDIED

5. ANALYSIS OF VIRULENCE
DETERMINANTS
• Animal models are preferred -need to be
studied invivo
• Organisms express some protein only when
they are in contact with some cells
• Invitro studies can also be done but the
cultural conditions should mimic those found
in the host

6. • Bacteria produce virulence determinants only
at times of crisis
• E.g Iron limitation in host cells causes the
production of haemolysin by E.coli and
Diphtheria toxin from Corynebacterium
diphtheriae

7. HOW BACTERIA
REGULATE THE
PRODUCTION OF
VIRULENCE
PROTEINS

8. Quorum sensing
• Mechanism used by the bacteria to produce
virulence determinants only at the time of
crisis and to save energy
• Expression of virulence factors is associated
with production of inducer molecules or
phermones
• Accumulate as the bacteria grow

9. • Restriction of expression of genes only at high
cell densities at which the resulting
phenotype will be beneficial

11. Adhesion
• Adhesion- surface interaction between
specific structures on the mammalian cell
surface (Carbohydrates) and those on the
bacterial surface (Proteins)
• Fimbrial adhesins
• Non fimbrial adhesins
• Binding to fibronectin

12. Fimbrial adhesins
• Fimbriae are thin rod like structures which
mediate attachment of bacteria to host cells
• Fimbriae are classified based on their ability to
resist mannose
• Mannose sensitive fimbriae
and
• Mannose resistant fimbriae

13. • Antigenic composition of fimbriae is complex
• The composition of fimbrial antigens is based
on the target receptors at different anatomical
sites of the infected host
• E.g. Pyelonephrithogenic E.coli and
enteropathogenic E.coli will have fimbriae
with different fimbrial antigens

14. Non fimbrial adhesins
• Filamentous haemagglutinin of Bord.pertusis
• Fibrillar haemagglutinin of Helicobacter pylori
• Exopolysaacharides in the surface of bacteria
e.g. Streptococcus mutans synthesize a
homopolymer of glucose which anchors the
bacteria to the tooth surface
• Flagella also act as adhesins in case of Vibrio
cholerae

15. • Teichoic acid and surface proteins of
coagulase negative staphylococci helps them
adhere to prosthetic devices and catheters
thereby causing nosocomical infections

16. BINDING TO FIBRONECTIN
• Fibronectin is a complex glycoprotein found in
mucosal cell surface and in plasma
• Bacteria like Streptococcus pyogenes,
Staphylococcus aureus and Treponema
pallidium bind to fibronectin in the host
surface(Usually bind to amino terminal)

17. Consequences of adhesion
• Adhesion causes structural and functional
changes in mucosal cells
E.g. Enteropathogenic E.coli cause structural
changes which result in the loss of microvilli
Some bacterial adhesions triggers inflammatory
response also e.g H.pylori adhesion causes
production of IL-8

18. Capsule
• All the pathogens associated with meningitis
and pneumonia usually have capsule
• E.g H.influenzae, S.pneumoniae, Neisseria
menigitidis
• Capsules are polysaacharides made of
different sugar monomers

19. • Hydrophilic nature of the capsule hinders
phagocytosis
• Prevent efficient opsonization by preventing the
deposition of complement completely or away
from the bacterial membrane
• Capsules are less immunogenic
E.g. The capsule of Neisseria menigitidis closely
resembles the sialic acid of the brain

20. Streptococcal M protein
• Functions in a similar manner like capsule by
preventing complement deposition
• Binds with fibrin

21. MECHANISMS TO RESIST
PHAGOCYTOSIS

22. Antigenic variation

23. • Variation in surface protein antigen during the
course of infection helps in avoidance of
immune response
• Pathogenic Neisseria express this by
mutation of amino acids
Switching genes on and off i.e not
expressing all proteins at once

24. Immunoglobin proteases
• Pathogenic bacteria produce an enzyme that
can cleave Ig A

25. IRON ACQUISITION
• Bacteria need iron to survive but getting iron
from mammalian cells is not easy
Because the body has higher affinity iron binding
proteins like transferrin and lactoferrin
To acquire iron they use
extracellular iron chelators called siderophores
proteolytic cleavage of iron chelators of
mammalian cells

26. TOXINS
The classic pathology of the disease is due to the
toxins in many diseases
They can exert their effect directly
or
by production of immunological mediators which
inturn cause pathophysiological effects

27. TOXINS
EXOTOXINS
PRODUCED BY BOTH
GM POSITIVE AND
NEGATIVE BACTERIA
ENDOTOXINS OR
LIPOPOLYSAACHARIDES
FOUND IN THE CELL
WALL OF GM
NEGATIVE BACTERIA

28. ENDOTOXIN
• Released from the bacterial membrane
through outer membrane vesicles or blebs
following natural lysis of the bacterium
• On bacteriological media bacteria containing
LPS produces smooth colonies

29. STRUCTURE OF ENDOTOXIN
• three distinct domains
O-antigen region
core oligosaccharide
Lipid A

30. EXOTOXINS
• Diffusible proteins secreted into the external
medium by the pathogen
• Cause both physiological damage -cholera toxin
promotes electrolyte excretion from enterocytes
without killing them
and
pathological damage where the toxin inhibits
protein synthesis and causes cell death

31. CLASSIFICATION
• Type I – bind surface receptors and stimulate
transmembrane signals
• Type II-act directly on membranes,forming
pores or disrupting lipid bilayers
• Type III-translocate an active enzymatic
component into the cell thereby modifying an
intracellular target molecule