Brief description of bacterial virulence

1. Mechanism of Bacterial Pathogenesis
and Virulence
Dr Meher Rizvi
Deptt of Microbiology and
Immunology

2. Bacterial Virulence Factors

3. Objectives
List various factors viz: bacterial cell structures,
toxins and enzymes which different bacteria produce
Discuss the role of these factors in causation of
human disease

4. BACTERIAL VIRULENCE

5. Definitions
Commensals:
Harmless microbes living on the host and causing no ill
effect/injury to the host.
Pathogens:
Microbes capable of causing disease
Infection:
Growth and multiplication of a microbe in or on the body
with or without the production of disease.
Colonization:
Pathogen enters, multiplies, does not invade

6. Pathogenicity:
The capacity of a bacterium to cause disease
Virulence:
The measure of the pathogenicity of a microorganism.
Invasiveness :
The ability of the pathogen to invade the tissues.
Opportunistic pathogens:
Cause disease in immunocompromised people (HIV, Solid
organ transplant patient, Chemotherapy.

7. Strict pathogens
are more virulent and can
cause diseases in a
normal person.
Opportunistic pathogens
are typically members of
normal flora and cause
diseases when they are
introduced into
unprotected sites; usually
occur in people with
underlying conditions.

8. Mode of transmission
Entry into human body-
 Ingestion : ( food or water )
 Salmonella typhi
 Shigella dysenteriae
 Vibrio cholerae
 Inhalation: ( Respiratory Tract )
 Mycobacterium tuberculosis:
 Streptococcus pneumonia
 Haemophilus influenzae
Kills around 2 million people in a year
Kills around 6 million children in a year

9.  Direct contact
 Unclean hands: Common cold, skin and eye infections
 Break in the skin ( wounds): Staphylococcus aureus
 Burns: Pseudomonas aerugunosa
 Trauma (RTA) : Clostridium tetani
 Sexual transmission :
 Neisseria gonorrhoeae ( gonorrhea )
 Treponema pallidum ( syphilis )
 Chlamydia trachomatis

10.  Blood borne transmission
 Needle stick injuries / Blood transfusion / Intravenous drug abuse:
HIV, HBV, HCV
 Vector borne:
Mechanical: Flies spreading bacteria to food ( Salmonella/ shigella)
Biological: Y. pestis multiplying in flea gut
 Vertical transmission Mechanical vectors-
 Treponema pallidum ( syphilis )
 Toxoplasma
 Cytomegalovirus

11. Infective dose
• Low infective dose : Shigella ( Just 10 bacilli)
Resistant to stomach acidity
• Large infective dose: Vibrio cholera 106-108

12. 1. Transmissibility
2. Adherence to host cells
3. Invasion of host cells and tissue
4. Evasion of the host immune system
5. Toxigenicity
Characteristics of Pathogenic Bacteria

13. Bacterial virulence factors
PHENOTYPIC
• Colonization factors
• Adherence
• Motility
• Evasion of host immune
response
• Capsule
• IgA proteases
• Intracellular residence
• Antigenic heterogenicity
• Biofilm formation
• Toxin production
• Endotoxin
• Exotoxon
• Enzymes
• Bacteriocins
GENOTYPIC
• Bacteriophage
• Plasmid
• Transposon

14. Colonization factors
1. Adherence
• Adherence of bacteria to epithelial / endothelial cells allows
them to colonize the tissue.
1. Pili (fimbriae) : binds to glycolipids or glycoproteins
2. Adhesins : M protein in Streptococci pyogenes, lipoteichoic
acids in Gram positive bacteria
3. Biofilms : ( Adhere strongly to catheters, heart valves, knee
joint replacement prosthesis)

15. 3. Adhesins/afimbrial adhesins
• Proteins that promote the tighter binding of
bacteria to host cell following initial binding by
pili.
• Fibronectin, vitronectins
• M proteins
• Lipoteichoic acid

17. 2. Pili/fimbriae
• Organ of adhesion. Enhances virulence
• Sex pili help in bacterial gene transfer: Conjugation
• Other methods of genetic transfer:
• Transduction: Transfer through bacteriophages
• Transformation: Picking up DNA from the environment

18. Encapsulation (Inhibition of phagocytosis and serum bactericidal
effect)
e.g. Neisseria meningitis, Streptococcus pneumoniae
Antigenic or phase variation (Borrelia burgdorferii, Salmonella typhi)
Intracellular multiplication (M. tuberculosis, Salmonella typhi)
Production of anti-immunoglobulin protease (IgA protease)
Inhibition of chemotaxis (C5a peptidase)
Destruction of phagocytes
Microbial defenses against host
immunologic clearance

19. Antigenic variation: Borrelia burgdorferii

20. Capsule
• A capsule is a loose, relatively unstructured network of
polymers that covers the surface of an organism.
• Main role of capsular polysacharide is
1. Protection against phagocyte mediated destruction.
2. Protection from complement activaton.

21. IgA PROTEASES
• IgA is the secretory antibody on mucosal surfaces.
Examples
N.meningitidis
N.gonorrhoeae
H.influenzae
S.pneumoniae,

22. Virulence markers S. pyogenes:
C5a peptidase, Enzymes, Toxins, M prt

23. INTRACELLULAR RESIDENCE
M. tuberculosis, Brucella species and Legionella species live and
grow in the hostile environment within PMN.
The bacteria accomplish this by several mechanism:
a) Produce toxic proteins that kill phagocytes on arrival
b) Avoid entry into the phagosome. Live within the cytosol of the
phagocyte.
c) Prevent phagosome-lysosome fusion. Live within the
phagosome.
d) Resistant to lysosomal enzymes. Survive within the
phagolysosomes

24. Phagocytosis

25. Survival in phagocytes

26. BIOFILMS

28. BIOFILM FORMATION
• Biofilms are dense, multiorganism layers of bacteria
• First layer of bacteria attaches directly to the surface
of host cells
•
• Other layer of bacteria are attached to the basal layer
by a polysaccharide matrix.
• Non cellular materials such as mineral crystals,
corrosion particles, clay/silt or blood components are
deposited depending on the envelope in which it
develops.

29. TOXINS

30. Exotoxins :
 Proteins in nature, secreted out of bacterial cell
 Corynebacterium diphtheriae toxin
 Clostridium tetanii
 Vibrio cholerae toxin
 Staphylococcus aureus Enterotoxin
 Shigella dysenteriae toxin

31. Endotoxin :
 The lipo-polysachharide ( LPS ) component of Gram
negative bacterial outer membrane is called the Endotoxin
 Lipid A component of lipo-polysachharide ( LPS )
 Stimulates release of acute phase cytokines ( IL-1,
TNF- α and IL-6 ) and inflammatory reactions
 Leading to high fever, hypotension and shock

32. ENDOTOXIN
Lipopolysaccharide components of the outer membrane of the gram-ve bacteria.
LPS consists of 2 regions-
• A hydrophobic glycolipid (lipid A)
• A hydrophilic polysaccharide
Two forms-smooth and rough

33. ENDOTOXIN
1. Integral part of cell wall
2. Endotoxin is LPS; Lipid A is
toxic component
3. Heat stable
4. Antigenic; ??immunogenicity
5. Toxoids cannot be produced
6. Many effects on host
7. Produced by gram-negative
organisms only
8. Fever present
EXOTOXIN
1. Released from the cell before
or after lysis
2. Protein
3. Heat labile
4. Antigenic and immunogenic
5. Toxoids can be produced
6. Specific in effect on host
7. Produced by gram-positive
and gram-negative org.
8. No fever

34. Staphylococcus aureus: Virulence
factors

35. Enzymes:
• Bacteria release degradative enzymes, to breakdown host cells
and tissues
• Examples :
• Streptolysins, DNAases, and Streptokinases are produced by
Streptococcus pyogenes
• Fibrinolysin, Hyaluronidase, Coagulase and DNAases
produced by Staphylococcus aureus
• Lecithinase and collagenase- C. perfringens.

36. Extracellular Bacterial Proteins :Invasins
ActivityBacteria
Involved
Invasin
Degrades hyaluronic of
connective tissue
Streptococci,
staphylococci
and clostridia
Hyaluronidase
Dissolves collagen
framework of muscles
Clostridium
species
Collagenase
Degrades neuraminic acid
of intestinal mucosa
Vibrio
cholerae and
Shigella
dysenteriae
Neuraminidase

37. PLASMID
• Confers additional properties:
• Drug resistance,
• Bacteriocin production,
• Toxigenicity
• Confer on the host bacterium survival
advantage under appropriate conditions.

38. Mechanisms of acquiring bacterial
virulence genes

39. Bacterial Virulence Factors

40. Thank you