Transcript Microbiology

Chapter 15
Microbial
Mechanisms of
Pathogenicity
Copyright © 2010 Pearson Education, Inc.
Lectures prepared by Christine L. Case
Q&A
 Almost every
pathogen has a
mechanism for
attaching to host
tissues at their portal
of entry. What is this
attachment called,
and how does it
occur?
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Learning Objectives
Upon completion of this chapter, you should be able to:
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Identify the principle portals of entry and portals of exit
Use examples to explain how microbes adhere to host cells
Explain how capsules and cell walls contribute to pathogenicity
Compare the effects of coagulases, kinases, hyaluronidase, and collagenase
Define and give an example of antigenic variation
Describe how bacteria use the host cell’s cytoskeleton to enter the cell
Describe the function of siderophores
Provide an example of direct damage caused by bacteria and compare it to damage caused by release of
a toxin
Contrast the nature and effects of endotoxins and exotoxins
Outline the mechanisms of A-B toxins, membrane-disrupting toxins, and superantigens.
Classify the following using type of toxin and effects on the body: Diptheria toxin, Erythrogenic toxin,
Botulinum toxin, Tetanus toxin, Vibrio enterotoxin, and Staphylococcal enterotoxin
Differentiate between shock and septic shock
Using examples, describe the roles of plasmids and lysogeny in pathogenicity
List nine cytopathic effects of viral infections
Discuss the causes of symptoms due to infection with fungi, protozoans, helminthic, and algal pathogens
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Mechanisms of Pathogenicity
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Figure 15.9
Mechanisms of Pathogenicity
 Pathogenicity: The ability to cause disease
 Virulence: The extent of pathogenicity
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Portals of Entry
 Mucous membranes
 Respiratory tract, GI tract, Genitourinary tract
 Skin
 Parenteral route (piercing skin or mucous
membranes)
 Every microbe has a preferred portal of entry!
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Numbers of Invading Microbes
 ID50: Infectious dose for 50% of the test
population
 LD50: Lethal dose for 50% of the test population
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Bacillus anthracis
Portal of Entry
Skin
Inhalation
Ingestion
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ID50
10–50
endospores
10,000–20,000
endospores
250,000–
1,000,000
endospores
LD50
Unknown, but
rarely lethal
Unknown, but
high mortality
rate
Unknown and
rare, but high
mortality rate
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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Adherence
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Figure 15.1
Adherence
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Figure 15.1
Adherence
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Figure 15.1
Q&A
 Almost every
pathogen has a
mechanism for
attaching to host
tissues at their portal
of entry. What is this
attachment called,
and how does it
occur?
 Answer:
adhesins/ligands – bind
to host cell receptors
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Virulence Contributors
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Capsules
Cell Wall Components
Enzymes
Membrane Ruffling
Antigenic Variation
Penetration of Cytoskeleton
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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
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Coagulase: Coagulates fibrinogen
Kinases: Digest fibrin clots
Hyaluronidase: Hydrolyzes hyaluronic acid
Collagenase: Hydrolyzes collagen
IgA proteases: Destroy IgA antibodies
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Antigenic Variation
 Alter surface proteins
ANIMATION Virulence Factors: Hiding from Host Defenses
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Figure 22.16
Membrane Ruffling
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Figure 15.2
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 15.2
How Pathogens Damage Host
 Using the host’s nutrients / Metabolizing the host
 Direct Damage v. toxin damage
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Using the Host’s Nutrients:
Siderophores
 Use host’s iron
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Figure 15.3
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
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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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Exotoxins and Endotoxins
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Figure 15.4
Exotoxins
 Specific for a structure or function in host cell
ANIMATION Virulence Factors: Exotoxins
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Figure 15.4a
The Action of an A-B Exotoxin
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Figure 15.5
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
 Example: Exotoxin/enterotoxin produced by S. aureus
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Exotoxin
Source
Relation to microbe
Chemistry
Mostly Gram +
By-products of growing cell
Protein
Fever?
No
Neutralized by antitoxin?
Yes
LD50
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Small
Figure 15.4a
Exotoxins & Lysogenic Conversion
Cells only produce toxin when infected by bacteriophage;
bacteriophage induces phenotypic change
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
Outer membrane
Lipid A
Fever?
Yes
Neutralized by Antitoxin?
No
LD50
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Relatively large
Figure 15.4b
Endotoxins and the Pyrogenic
Response
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Figure 15.6
LAL Assay
 Limulus amoebocyte lysate assay – tests for
presence and amount of endotoxin
 Amoebocyte lysis produces a clot
 Endotoxin causes lysis
ANIMATION Virulence Factors: Endotoxins
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Development of pathogenicity
 Plasmids
 Can carry R factors, toxins, code for production of
capsules and fimbriae
 Lysogenic conversion
 Viral genome incorporation can carry virulence factors
from other harmful bacteria, resulting in a weak strain
becoming virulent.
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Check Your Understanding
 Washwater containing Pseudomonas was
sterilized and used to wash cardiac catheters.
Three patients developed fever, chills, and
hypotension following cardiac catheterization.
The water and catheters were sterile. Why did
the patients show these reactions? How should
the water have been tested?
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Cytopathic Effects of Viruses
 Growth inside of cells protects them from damage
 Some viruses cause cytocidal (death) effects while
other cause non-cytocidal (damage) effects
 Examples: stopping mitosis, lysis, formation of inclusion
bodies (viral parts), cell fusion (syncytium), production of
interferons, antigenic changes in the host cell so they are
not recognized by the body anymore, chromosomal
changes (creating oncogenes), and transformation (cells
don’t recognize boundaries anymore and divide
uncontrollably)
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Cytopathic Effects of Viruses
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Figure 15.7
Cytopathic Effects of Viruses
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Figure 15.8
Pathogenic Properties of Fungi
 Fungal waste products may cause symptoms
 Chronic infections provoke an allergic response
 Tichothecene toxins (mycotoxins) inhibit protein
synthesis
 Fusarium
 Proteases
 Candida, Trichophyton
 Capsule prevents phagocytosis
 Cryptococcus
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Pathogenic Properties of Fungi
 Ergot toxin – effects similar to LSD
 Claviceps
 Aflatoxin – potentially carcinogenic
 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; type of neurotoxin
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Figure 27.13
Portals of Exit
 Respiratory tract
 Coughing and sneezing
 Gastrointestinal tract
 Feces and saliva
 Genitourinary tract
 Urine and vaginal secretions
 Skin
 Blood
 Biting arthropods and needles or syringes
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