MICROBIOLOGY Chapter 15 Microbial Mechanisms of Pathogenicity Dr. Abdelraouf A. Elmanama Ph. D Microbiology Medical Technology Department, Faculty of Science, Islamic University-Gaza 2008 • Microbial Mechanisms of Pathogenicity Pathogenicity The ability to cause disease • Virulence 2008 The extent of pathogenicity Portals of Entry • Mucous membranes • Skin • Parenteral route 2008 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 2008 Bacillus anthracis 2008 Portal of entry Skin ID50 10-50 endospores Inhalation 10,000-20,000 endospores Ingestion 250,000-1,000,000 endospores Adherence • Adhesions/ligands bind to receptors on host cells 2008 • Glycocalyx Streptococcus mutans • Fimbriae Escherichia coli • M protein Streptococcus pyogenes • Opa protein Neisseria gonorrhoeae • Tapered end Treponema pallidum Enzymes 2008 • Coagulase Coagulate blood • Kinases Digest fibrin clots • Hyaluronidase Hydrolyses hyaluronic acid • Collagenase Hydrolyzes collagen • IgA proteases Destroy IgA antibodies • Siderophores Take iron from host ironbinding proteins • Antigenic variation Alter surface proteins Penetration into the Host Cell 2008 Figure 15.2 Toxins • Toxin Substances that contribute to pathogenicity • Toxigenicity Ability to produce a toxin • Toxemia Presence of toxin the host's blood • Toxoid Inactivated toxin used in a vaccine • Antitoxin Antibodies against a specific toxin 2008 Endotoxin 2008 Figure 15.4b Exotoxin Source Metabolic product Chemistry By-products of growing cell Protein Fever? No Neutralized by antitoxin Yes LD50 2008 Mostly Gram + Small Exotoxins • A-B toxins or type III toxins 2008 Figure 15.5 Exotoxins • Superantigens or type I toxins • Cause an intense immune response due to release of cytokines from host cells • Fever, nausea, vomiting, diarrhea, shock, death 2008 Exotoxins • Membrane-disrupting toxins or type II toxins • Lyse host’s cells by: • Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins) • Disrupting phospholipid bilayer 2008 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 • Corynebacterium diphtheriae • Staphylococcus aureus 2008 Superantigen. Enterotoxin. + Exotoxins 2008 Figure 15.4a Endotoxins 2008 Figure 15.6 Endotoxins 2008 Source Gram– Metabolic product Present in LPS of outer membrane Chemistry Lipid Fever? Yes Neutralized by antitoxin No LD50 Relatively large Cytopathic Effects of Viruses 2008 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 2008 Pathogenic Properties of Fungi • Aflatoxin • Aspergillus • Mycotoxins • Neurotoxins: Phalloidin, amanitin • Amanita 2008 Pathogenic Properties of Protozoa • Presence of protozoa • Protozoan waste products may cause symptoms • Avoid host defenses by • Growing in phagocytes • Antigenic variation 2008 Pathogenic Properties of Helminths • Use host tissue • Presence of parasite interferes with host function • Parasite's metabolic waste can cause symptoms 2008 Pathogenic Properties of Algae • Neurotoxins produced by dinoflagellates • Saxitoxin • Paralytic shellfish poisoning 2008 Portals of Exit • Respiratory tract • Coughing, sneezing • Gastrointestinal tract • Feces, saliva • Genitourinary tract • Urine, vaginal secretions • Skin • Blood • Biting arthropods, needles/syringes 2008 Mechanisms of Pathogenicity 2008 Figure 15.9