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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