Download virulence factors

BACTERIAL VIRULENCE FACTORS
The ability to:
• 1. Adherence
• To host surfaces and not be washed off
• 2. Avoid phagocytosis
• Prevent host defenses from destroying
• 3. Penetrate
• Get into host and spread
• 4. Produce Enzymes
• Spread, prevent host defenses and
cause damage at or near site of
infection
• 5. Produce Toxins
• Cause damage at distant site
Virulence Factors
• 1. Adherence
• 2. Capsule
• 3. Enzymes
• leukocidins
• Hemolysins
• Coagulase
• Kinases
• Hyaluronidase
• Collagenase
• Necrotizing Factor
4. Toxins
Adherence
• Adhesions/ligands bind to receptors on host cells
so won’t get flushed off.
• Mechanisms to adhere and avoid host defenses:
• Glycocalyx
Streptococcus mutans
Dextran (plaque)
• Waxes
Mycobacteria
• Fimbriae
Escherichia coli
• M protein
Streptococcus pyogenes
• Tapered end w/ hooks Treponema pallidum
Capsules
Prevent phagocytosis
and help with attachment
(adherence)
• Streptococcus pneumoniae
• Klebsiella pneumoniae
• Haemophilus influenzae
• Bacillus anthracis
• Streptococcus mutans
• Yersinia pestis
Enzymes to help penetration
Many pathogens secrete enzymes that contribute to their
pathogenicity:
• Increase virulence by use of enzymes
• And avoid phagocytosis
• Coagulase
Coagulate blood - wall off from host
make boil
• Kinases
Digest fibrin clot - allow
spreading
streptokinase and staphylolinase
• Hyaluronidase
Hydrolyses hyaluronic
acid connective tissue
• Collagenase
Hydrolyzes collagen
• IgA proteases
Destroy IgA antibodies
• Hemolysins
lyse RBC’s
Hemolysins
Alpha Hemolytic Streptococci
- secrete hemolysins that cause the incomplete
lysis or RBC’s
Beta Hemolytic Streptococci
- secrete hemolysins that cause the complete lysis of
RBC’s
Leukocidins
• Enzymes that attack certain types of WBC’s
• 1. Kills WBC’s which prevents phagocytosis
• 2. Releases & ruptures lysosomes
• lysosomes - contain powerful hydrolytic enzymes
which then cause more tissue damage
Enzymes: Necrotizing Factor
“Flesh Eating Bacteria”
Necrotizing fasciitis
causes death (necrosis) to tissue cells
Toxins
Provide properties to spread and cause damage to the host.
Compare endotoxins and exotoxins
• Endotoxins from inside the cell. Released upon cell lysis.
• Exotoxins are secreted out of the cell during cell life.
• Toxin
Substances that contribute to
pathogenicity
• Toxigenicity
Ability to produce a toxin
• Toxemia
Presence of toxin the host's blood
• Toxoid
Inactivated toxin used in a vaccine
• Antitoxin
Antibodies against a specific toxin
Exotoxins
Seen in both Gram positive and Gram negative
bacteria
Figure 15.4a
Exotoxin
Exotoxin
Source
Metabolic product
Chemistry
Fever?
Neutralized by antitoxin
LD50
Mostly Gram positive
By-products of growing cell
Protein
Water soluble
No
Yes
Small - Very potent
1 mg of Clostridium botulinum toxin
can kill 1 million guinea pigs
Exotoxins - three types
• 1. Cytotoxins
• kill cells
• 2. Neurotoxins
• interfere with normal nerve
impulses
• 3. Enterotoxins
• effect cells lining the G.I.
Tract
Many toxins have A-B subunit toxins
or type III toxins
• A - active
• Causes change in
host
• B - binding
Figure 15.5
Exotoxins
• Superantigens or type I toxins
• Cause an intense immune response due to release
of cytokines from host cells
• Fever, nausea, vomiting, diarrhea, shock, death
Exotoxins
• Membrane-disrupting toxins or type II toxins
• Lyse host’s cells by:
• Making protein channels in the plasma
membrane (e.g., leukocidins, hemolysins)
• Disrupting phospholipid bilayer
Cholera
enterotoxin
•Vibrio cholerae
•Gram (-) comma shaped rods
Exotoxins
Exotoxin
Lysogenic
conversion
A-B toxin type III. Inhibits
protein synthesis.
+
• Streptococcus pyogenes
Membrane-disrupting. Type II
Erythrogenic.
+
• Clostridium botulinum
A-B toxin. Neurotoxin - flaccid
paralysis
+
• Corynebacterium diphtheriae
• C. tetani
• Vibrio cholerae
• Staphylococcus aureus
A-B toxin. Neurotoxin - prevents
CNS inhibition - spastic
paralysis
A-B toxin. Enterotoxin.
Stimulates cAMP to cause
severe diarrhea
Superantigen. Type I.
Enterotoxin.
+
Botox
• Botulism
• Clostridium botulinum
• Gram (+), anaerobic, spore-forming rod, found in soil
• works at the neuromuscular junction
• prevents impulse from nerve cell to muscle cell
• results in muscle paralysis
•
Botulus – latin word for sausage (first known as sausage disease) C.
botulinum does not grow in sausage today mainly due to nitrites added.
Infant botulism 250 per yr., most associated with honey due to little
microbial flora in G.I.
Tetanus (Lock Jaw)
• Clostridium tetani
• Gram (+), spore-forming,
anaerobic rod
• neurotoxin acts on
nerves, resulting in the
inhibition of muscle
relaxation
• Tetanospasmin “spasms” or “Lock Jaw”
Endotoxin
Figure 15.4b
Endotoxins
Source
Gram negative
Metabolic product
Present in LPS of outer membrane
Chemistry
Lipid
Fever?
Yes
Neutralized by antitoxin
No
LD50
Relatively large
Endotoxins - part of the Gram (-) Bacterial cell wall
• LPS (Lipopolysaccharides)
• O Antigen
• Lipid A
• Heat Stable (exotoxins are typically heat liable)
• Lipid A - Toxin portion of the LPS
• responsible for Fever that is associated
with many Gram (-) Bacterial infections
• Gram (-) cells are “digested” endotoxins
are released – fever
Endotoxins
Figure 15.6