BACTERIAL VIRULENCE

FACTORS

HIBA SALEEM
LECTURER
 BACTERIAL VIRULENCE FACTORS
 Virulence factors are important for microbial pathogenesis.
 Virulence factors are bacteria-associated molecules that are required for a
bacterium to cause disease while infecting eukaryotic hosts such as humans.

 The environments outside the body have evolved complex signal transduction systems
to regulate the genes important for virulence.
 Environmental signals often control the expression of the virulence genes.
 Common signals includes;
1. Temperature
2. Iron availability
3. Osmolality
4. Growth phase
5. pH
6. Specific ions (eg, Ca2+) or nutrient factors.
 VIRULENCE FACTORS
 Virulence factors are the molecules that assist the bacterium colonize the host at the
cellular level. These factors are either secretory, membrane associated or cytosolic in
nature.

 The following are the most common virulence factors which includes;

 Adherence and Colonization Factors- adhere to a mucosal surface

 Invasion Factors.

 Capsules and Other Surface Components.

 Endotoxins.

 Enzymes.
 1). ADHERENCE AND COLONIZATION FACTOR

Adherence, which is only one step in the infectious process, is followed by development of
microcolonies and subsequent steps in the pathogenesis of infection.

1. Capsules
2. Slime layers
3. Surface carbohydrates
4. Protein
5. Flagella
6. Pilli
 BACTERIAL APPENDAGES
 Bacteria also have specific surface molecules that interact with host cells.
 Many bacteria have pili, (thick rodlike appendages) or fimbriae, (shorter hairlike)
structures that extend from the bacterial cell surface and help mediate
adherence of the bacteria to host cell surfaces
FIMBRIAE vs PILI
 EXAMPLES
• E. coli strains have Type 1 pili, which adhere to Epithelial Cell receptors.
• The E. coli that causes diarrheal diseases have pilus (fimbriae)-mediated
adherence to intestinal epithelial cells.

Specific ligand-receptor mechanisms have evolved to promote bacterial

adherence to host cells.
Example: Group A streptococci (Streptococcus pyogenes)- fimbriae that extend
from the cell surface.

Lipoteichoic acid
The lipoteichoic acid and Protein F cause
Protein F
adherence of the streptococci to buccal epithelial cells.
M protein
 ADHERENCE AND COLONIZATION FACTOR

• After adherence occurs, conformational changes in the host cell ensure that

can lead to cytoskeletal changes allowing organism uptake by the cell.

• Sometimes, changes in the adhesin molecule after attachment may trigger

activation of virulence genes that promote invasion or that result in other

pathogenic changes.
 2. INVASION FACTORS
Invasion is the term commonly used to describe the entry of bacteria into host
cells and for many disease-causing bacteria, invasion of the host’s epithelium is
central to the infectious process.

 Some bacteria (eg, Salmonella species) invade tissues through the junctions between
epithelial cells.

 In many infections, the bacteria produce virulence factors that cause the host cells to
engulf (ingest) the bacteria. The host cells play a very active role in the process.

 When inside the host cell, bacteria may remain enclosed in a vacuole composed of the
host cell membrane, or the vacuole membrane may be dissolved and bacteria may be
dispersed in the cytoplasm.

 Toxin production and other virulence properties are generally independent of the ability
of bacteria to invade cells and tissues.

For example, C. diphtheriae is able to invade the epithelium of the nasopharynx

and cause symptomatic sore
INVASION OF HOST CELL AND TISSUE
 3. TOXINS

 Toxins produced by bacteria are generally classified into two

groups

1. Endotoxin, which is present in the outer membrane of gram-

negative rods.
2. Exotoxin- Toxins that are secreted, such as enterotoxins and
exotoxins.

Enterotoxins and exotoxins are often classified by mechanisms of

action and the impact on host cells.
3. BACTERIAL TOXINS
 3. BACTERIAL TOXINS
Exotoxin Endotoxin
1. They are protein (polypeptide) in nature The are lipopolysaccharide in nature
2. Heat Labile (>60 °C) Heat Stable
3. Actively secreted by living cell Form integral part of cell wall and released
only on disruption of bacterial cell.
4. They are converted into toxoid by They cannot be toxoided
formaldehyde
5. Enzymic in action Not enzymic in action
6. They have specific pharmacological effect for Non specific action of all endotoxin
each toxin
7. They have high potency They have low potency
8. They are highly specific for particular tissue.TT They are non specific in action.
(Tetanus toxin for CNS)
9. They don't produce fever in host They usually produce fever
10. They are mainly produced by Gram positive They are produced by Gram-negative
and also by some Gram negative bacteria bacteria
 A). EXOTOXINS
 Many exotoxins consist of
A and B subunits.
(Binary toxins
Type III toxins).

 The B subunit generally

mediates adherence of
the toxin complex to a
host cell and aids
entrance of the exotoxin
into the host cell.

 The A subunit provides

the toxic activity.
 Examples
Organism ExoToxin Disease

Corynebacterium diphtheriae Diphtheria toxin Diphtheria

Clostridium tetani Tetanus Toxin Tetanus

(Tetanospasmin)

Clostridium botulinum Botulinum toxin Botulism

Clostridium perferingens Alpha toxin Gas gangrene

Staphylococcus aureus Toxic Shock Syndrome Toxin-1 Epidermal Toxin

(TSST-1) Toxic Shock
Syndrome
 A. EXOTOXIN (ENTEROTOXIN)
Exotoxins associated with diarrheal diseases are frequently called
enterotoxins and many belong to the type III toxin family.
 B. ENDOTOXIN
Endotoxin, a lipopoly-saccharide found in the cell wall of Gram-negative bacteria,
is a pyrogen which induces inflammation and fever as an immune response in
higher organisms.

The LPS (endotoxin) of gram-negative bacteria are bacterial cell wall components
that are often liberated when the bacteria lyse.
B. ENDOTOXIN
 B. ENDOTOXIN
• The lipid A domain is the region recognized by the immune
system and is the component that is responsible for cytokine
stimulation
• The other two components are an oligosaccharide core and
an outermost O-antigen polysaccharide.
 4. ENZYMES (Tissue-Degrading Enzyme)
ENZYME ORGANISM MAJOR EFFECT

Collagenase Clostridium perferingens Degrades Collagen (Major

(Proteolytic enzyme) fibrous connective tissue)

Coagulase S. aureus Formation of fibrin walls

Hyaluronidases Staphylococci, Streptococci Affects connective tissue

Streptokinase Streptococci Lysis of fibrin

Cytolysins Many bacteria Dissolve cells

Hemolysin Many bacteria Affect RBCs

Leukocidins Many bacteria Kills leucocytes

Streptolysin O(Oxygen-labile) Streptococci Group A Hemolysis

Streptolysin S (Oxygen-stable) Streptococci Group A No hemolysis

 4. ENZYMES (IgA1 Protease)
• Immunoglobulin A is the secretory antibody on mucosal surfaces.

• It has two primary forms,

1. IgA1

2. IgA2

• IgA1 has a series of amino acids in the hinge region that are not present in IgA2.

• Some bacteria that cause disease produce enzymes, IgA1 proteases that

• Split IgA1 at specific proline–threonine or proline–serine bonds in the hinge region

and inactivate its antibody activity.

FUNCTION

Production of IgA1 protease allows pathogens to inactivate the primary antibody found

on mucosal surfaces and thereby eliminate protection of the host by the antibody.
4. ENZYMES (IgA1 Protease)
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