Transcript Microbiology - Imperial Valley College

Chapter 15
Microbial
Mechanisms of
Pathogenicity
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Lectures prepared by Christine L. Case
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Mechanisms of Pathogenicity
 Pathogenicity: the ability to cause disease
 Virulence: the extent of pathogenicity
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Portals of Entry




Mucous membranes
Skin
Parenteral route
Preferred portal of entry
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Numbers of Invading Microbes
 ID50: infectious dose for 50% of the test
population
 LD50: lethal dose (of a toxin) for 50% of the test
population
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Bacillus anthracis
Portal of Entry
Skin
ID50
10–50 endospores
Inhalation
10,000–20,000 endospores
Ingestion
250,000–1,000,000
endospores
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Toxins
Portal of Entry
Botulinum
Shiga toxin
Staphylococcal enterotoxin
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ID50
0.03 ng/kg
250 ng/kg
1350 ng/kg
Adherence
 Adhesins/ligands bind to receptors on host cells
 Glycocalyx: Streptococcus mutans
 Fimbriae: Escherichia coli
 M protein: Streptococcus pyogenes
 Form biofilms
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Figure 15.1a Adherence.
Adhesin (ligand)
Pathogen
Host
cell
surface
Receptor
Surface molecules on a pathogen, called adhesins or
ligands, bind specifically to complementary surface receptors
on cells of certain host tissues.
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Figure 15.1b-c Adherence.
E. coli bacteria (yellow-green) on
human urinary bladder cells
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Bacteria (purple) adhering to
human skin
Capsules
 Prevent phagocytosis
 Streptococcus pneumoniae
 Haemophilus influenzae
 Bacillus anthracis
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Cell Wall Components
 M protein resists phagocytosis
 Streptococcus pyogenes
 Opa protein inhibits T helper cells
 Neisseria gonorrhoeae
 Mycolic acid (waxy lipid) resists digestion
 Mycobacterium tuberculosis
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Enzymes





Coagulase: coagulates fibrinogen
Kinases: digest fibrin clots
Hyaluronidase: hydrolyzes hyaluronic acid
Collagenase: hydrolyzes collagen
IgA proteases: destroy IgA antibodies
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Chapter 15, unnumbered figure A, p. 434.
Blocked coronary artery
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Chapter 15, unnumbered figure B, p. 434.
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Necrotizing fasciitis
Chapter 15, unnumbered figure C, p. 434.
Mechanism of streptokinase
Streptokinase
Plasminogen
Blood
clot
Plasmin
Fibrin
breakdown
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Figure 15.2 Salmonella entering intestinal epithelial cells as a result of ruffling.
Ruffling of
host cell
plasma
membrane
Salmonella
typhimurium
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Figure 22.16 How trypanosomes evade the immune system.
Clone B
Clone C
Relative number of trypanosomes
Clone A
0
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1
2
Weeks after infection
3
4
Penetration into the Host Cell
Cytoskeleton
 Invasins
 Salmonella alters host actin to enter a host cell
 Use actin to move from one cell to the next
 Listeria
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Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus.
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Figure 15.3 Structure of enterobactin, one type of bacterial siderophore.
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Direct Damage
 Disrupt host cell function
 Produce waste products
 Toxins
ANIMATION Virulence Factors: Penetrating Host Tissues
ANIMATION Virulence Factors: Enteric Pathogens
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The Production of Toxins





Toxin: substance that contributes to pathogenicity
Toxigenicity: ability to produce a toxin
Toxemia: presence of toxin in the host’s blood
Toxoid: inactivated toxin used in a vaccine
Antitoxin: antibodies against a specific toxin
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Figure 15.4 Mechanisms of Exotoxins and Endotoxins.
exotoxins
endotoxins
Exotoxins are proteins produced inside
pathogenic bacteria, most commonly grampositive bacteria, as part of their growth and
metabolism. The exotoxins are then
secreted into the surrounding medium
during log phase.
Endotoxins are the lipid portions of
lipopolysaccharides (LPS) that are part of
the outer membrane of the cell wall of gramnegative bacteria (lipid A; see Figure 4.13c).
The endotoxins are liberated when the
bacteria die and the cell wall breaks apart.
Cell wall
Exotoxin: toxic
substances released
outside the cell
Clostridium botulinum,
an example of a grampositive bacterium that
produces exotoxins
Salmonella typhimurium,
an example of a gramnegative bacterium that
produces endotoxins
Endotoxins: toxins
composed of lipids
that are part of the
cell membrane
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Exotoxins
 Specific for a structure or function in host cell
ANIMATION Virulence Factors: Exotoxins
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Figure 15.5 The action of an A-B exotoxin.
DNA
Exotoxin
mRNA
A (active)
A
B (binding) B
1
Bacterium
produces and
releases exotoxin.
2
B (binding)
component of
exotoxin attaches
to host cell
receptor.
3
A-B exotoxin
enters host cell
by receptormediated
endocytosis.
4
A-B exotoxin
enclosed in
pinched-off
portion of plasma
membrane during
pinocytosis.
5
A-B components of
exotoxin separate.
The A component
alters cell function
by inhibiting
protein synthesis.
The B component
is released from
the host cell.
Exotoxin
polypeptides
Bacterium
A
B
Receptor
Plasma
membrane
Nucleus
Cytoplasm
Host cell
A
B
A
B
A
B
B
A
Protein
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Membrane-Disrupting Toxins
 Lyse host’s cells by
 Making protein channels in the plasma
membrane
– Leukocidins
– Hemolysins
– Streptolysins
 Disrupting phospholipid bilayer
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Superantigens
 Cause an intense immune response due to release
of cytokines from host cells
 Symptoms: fever, nausea, vomiting, diarrhea,
shock, and death
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Exotoxin
Source
Relation to microbe
Chemistry
Mostly gram-positive
By-products of growing cell
Protein
Fever?
No
Neutralized by antitoxin?
Yes
LD50
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Small
Exotoxins and Lysogenic Conversion
Exotoxin
Corynebacterium
diphtheriae
A-B toxin
Lysogeny
+
Streptococcus
pyogenes
Membrane-disrupting
erythrogenic toxin
+
Clostridium botulinum
A-B toxin; neurotoxin
+
C. tetani
A-B toxin; neurotoxin
Vibrio cholerae
A-B toxin; enterotoxin
+
Staphylococcus
aureus
Superantigen
+
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Endotoxins
Source
Relation to Microbe
Chemistry
Gram-negative
Outer membrane
Lipid A
Fever?
Yes
Neutralized by Antitoxin?
No
LD50
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Relatively large
Figure 15.6 Endotoxins and the pyrogenic response.
Macrophage
Nucleus
Endotoxin
Endotoxin
Hypothalamus of brain
Prostaglandin
Cytokines
Fever
Blood
vessel
Vacuole
Pituitary
gland
Bacterium
1
A macrophage ingests
a gram-negative
bacterium.
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2
The bacterium is
degraded in a vacuole,
releasing endotoxins
that induce the
macrophage to
produce cytokines IL-1
and TNF-.
3
4
The cytokines are
released into the
bloodstream by the
macrophages,
through which they
travel to the
hypothalamus of the
brain.
The cytokines induce
the hypothalamus to
produce prostaglandins,
which reset the body’s
“thermostat” to a
higher temperature,
producing fever.
LAL Assay
 Limulus amebocyte lysate assay
 Amebocyte lysis produces a clot
 Endotoxin causes lysis
ANIMATION Virulence Factors: Endotoxins
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Figure 15.7 Some cytopathic effects of viruses.
Inclusion body
Cytoplasmic mass
Nuclei
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Figure 15.8 Transformed cells in culture.
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Pathogenic Properties of Fungi
 Fungal waste products may cause symptoms
 Chronic infections provoke an allergic response
 Trichothecene toxins inhibit protein synthesis
 Fusarium
 Proteases
 Candida, Trichophyton
 Capsule prevents phagocytosis
 Cryptococcus
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Pathogenic Properties of Fungi
 Ergot toxin
 Claviceps
 Aflatoxin
 Aspergillus
 Mycotoxins
 Neurotoxins: phalloidin, amanitin
 Amanita
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Pathogenic Properties of Protozoa
 Presence of protozoa
 Protozoan waste products may cause symptoms
 Avoid host defenses by
 Growing in phagocytes
 Antigenic variation
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Pathogenic Properties of Helminths
 Use host tissue
 Presence of parasite interferes with host function
 Parasite’s metabolic waste can cause symptoms
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Pathogenic Properties of Algae
 Paralytic shellfish poisoning
 Dinoflagellates
 Saxitoxin
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Figure 27.13 A red tide.
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Portals of Exit
 Respiratory tract
 Coughing and sneezing
 Gastrointestinal tract
 Feces and saliva
 Genitourinary tract
 Urine and vaginal secretions
 Skin
 Blood
 Arthropods that bite; needles or syringes
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Figure 15.9 Microbial Mechanisms of Pathogenicity.
When the balance between host and microbe is tipped in favor of the
microbe, an infection or disease results. Learning these mechanisms of
microbial pathogenicity is fundamental to understanding how pathogens
are able to overcome the host’s defenses.
H1N1 flu virus
portals of entry
Mucous membranes
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• Conjunctiva
Skin
Parenteral route
Number of
invading
microbes
penetration
or evasion of
host defenses
Capsules
Cell wall components
Enzymes
Antigenic variation
Invasins
Intracellular growth
Adherence
Mycobacterium
intracellulare
Clostridium
tetani
Micrographs
are not shown
to scale.
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damage to
host cells
Siderophores
Direct damage
Toxins
• Exotoxins
• Endotoxins
Lysogenic conversion
Cytopathic effects
portals of exit
Generally the same as
the portals of entry for a
given microbe:
• Mucous membranes
• Skin
• Parenteral route