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Transcript
Chapter 8
Microbial Mechanisms of
Pathogenicity
Microbial Mechanisms of
Pathogenicity
• Pathogenicity: The ability to cause
disease.
• Virulence: The extent of pathogenicity.
Portals of Entry
• Mucous membranes
• Skin
• Parenteral route
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.
Bacillus Anthracis
Portal of Entry
ID50
Skin
10-50 endospores
Inhalation
10,000-20,000 endospores
Ingestion
250,000-1,000,000 endospores
Toxins
Portal of Entry
Botulinum
Shiga toxin
Staphylococcal enterotoxin
ID50
0.03 ng/kg
250 ng/kg
1350 ng/kg
Adherence
• Adhesions/ligands bind to receptors on host
cells
– Glycocalyx: Streptococcus mutans
– Fimbriae: Escherichia coli
– M protein: Streptococcus pyogenes
– Opa protein: Neisseria gonorrhoeae
– Tapered end: Treponema pallidum
Adherence
Figure 15.1
Capsules
– Prevent phagocytosis
 Streptococcus pneumoniae
 Haemophilus influenzae
 Bacillus anthracis
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
Enzymes
– Coagulase: Coagulate blood
– Kinases: Digest fibrin clots
– Hyaluronidase: Hydrolyses hyaluronic acid
– Collagenase: Hydrolyzes collagen
– IgA proteases: Destroy IgA antibodies
– Siderophores: Take iron from host iron-binding
proteins
– Antigenic variation: Alter surface proteins
Penetration into the Host Cell
Figure 15.2
Toxins
• Toxin: Substances that contribute 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.
Endotoxins
Source:
Relation to microbe:
Gram –
Present in LPS of outer membrane
Chemistry:
Lipid
Fever?
Yes
Neutralized by antitoxin?
No
LD50:
Relatively large
Figure 15.4b
Exotoxin
Source:
Relation to microbe:
Chemistry:
Mostly Gram +
By-products of growing cell
Protein
Fever?
No
Neutralized by antitoxin?
Yes
LD50:
Small
Figure 15.4a
The Action of an A-B Exotoxin
Figure 15.5
Exotoxins
• Membrane-disrupting toxins
– Lyse host’s cells by
• Making protein channels in the plasma membrane
(e.g., leukocidins, hemolysins).
• Disrupting phospholipid bilayer.
Exotoxins
• Superantigens
– Cause an intense immune response due to
release of cytokines from host cells.
– Fever, nausea, vomiting, diarrhea, shock, and
death.
Exotoxins
• Specific for a structure or function in host
cell
Figure 15.4a
Exotoxins
Exotoxin
Lysogenic
conversion
A-B toxin.
Inhibits protein synthesis.
+
Streptococcus pyogenes
Membrane-disrupting.
Erythrogenic.
+
Clostridium botulinum
A-B toxin. Neurotoxin
+
C. tetani
A-B toxin. Neurotoxin
Vibrio cholerae
A-B toxin. Enterotoxin
+
Superantigen.
+
Corynebacterium diphtheriae
Staphylococcus aureus
Endotoxins
Figure 15.6
Cytopathic Effects of Viruses
Table 15.4
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
• Ergot toxin
– Claviceps
Pathogenic Properties of Fungi
• Aflatoxin
– Aspergillus
• Mycotoxins
– Neurotoxins: Phalloidin, amanitin
• Amanita
Pathogenic Properties of
Protozoa
• Presence of protozoa.
• Protozoan waste products may cause
symptoms.
• Avoid host defenses by
– Growing in phagocytes
– Antigenic variation
Pathogenic Properties of
Helminths
• Use host tissue.
• Presence of parasite interferes with host
function.
• Parasite's metabolic waste can cause
symptoms.
Pathogenic Properties of Algae
• Paralytic shellfish poisoning
– Dinoflagellates
• Domoic acid intoxication
– Diatoms
Figure 27.15
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
Mechanisms of Pathogenicity
Figure 15.9