13. Patogenicity

Transcription

13. Patogenicity
Microbial Mechanisms of Pathogenicity
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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
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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
Agent
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
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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Membrane Ruffling
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Figure 15.2
Antigenic Variation
 Alter surface proteins
ANIMATION Virulence Factors: Hiding from Host Defenses
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Figure 22.16
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
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
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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
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
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 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
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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Mechanisms of Pathogenicity
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Figure 15.9