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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? Copyright © 2010 Pearson Education, Inc. Learning Objectives Upon completion of this chapter, you should be able to: 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 Copyright © 2010 Pearson Education, Inc. Mechanisms of Pathogenicity Copyright © 2010 Pearson Education, Inc. Figure 15.9 Mechanisms of Pathogenicity Pathogenicity: The ability to cause disease Virulence: The extent of pathogenicity Copyright © 2010 Pearson Education, Inc. 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! Copyright © 2010 Pearson Education, Inc. Numbers of Invading Microbes ID50: Infectious dose for 50% of the test population LD50: Lethal dose for 50% of the test population Copyright © 2010 Pearson Education, Inc. Bacillus anthracis Portal of Entry Skin Inhalation Ingestion Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Adherence Copyright © 2010 Pearson Education, Inc. Figure 15.1 Adherence Copyright © 2010 Pearson Education, Inc. Figure 15.1 Adherence Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Virulence Contributors Capsules Cell Wall Components Enzymes Membrane Ruffling Antigenic Variation Penetration of Cytoskeleton Copyright © 2010 Pearson Education, Inc. Capsules Prevent phagocytosis Streptococcus pneumoniae Haemophilus influenzae Bacillus anthracis Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Enzymes Coagulase: Coagulates fibrinogen Kinases: Digest fibrin clots Hyaluronidase: Hydrolyzes hyaluronic acid Collagenase: Hydrolyzes collagen IgA proteases: Destroy IgA antibodies Copyright © 2010 Pearson Education, Inc. Antigenic Variation Alter surface proteins ANIMATION Virulence Factors: Hiding from Host Defenses Copyright © 2010 Pearson Education, Inc. Figure 22.16 Membrane Ruffling Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Figure 15.2 How Pathogens Damage Host Using the host’s nutrients / Metabolizing the host Direct Damage v. toxin damage Copyright © 2010 Pearson Education, Inc. Using the Host’s Nutrients: Siderophores Use host’s iron Copyright © 2010 Pearson Education, Inc. Figure 15.3 Direct Damage Disrupt host cell function Produce waste products Toxins ANIMATION Virulence Factors: Penetrating Host Tissues ANIMATION Virulence Factors: Enteric Pathogens Copyright © 2010 Pearson Education, Inc. The Production of Toxins 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 Copyright © 2010 Pearson Education, Inc. Exotoxins and Endotoxins Copyright © 2010 Pearson Education, Inc. Figure 15.4 Exotoxins Specific for a structure or function in host cell ANIMATION Virulence Factors: Exotoxins Copyright © 2010 Pearson Education, Inc. Figure 15.4a The Action of an A-B Exotoxin Copyright © 2010 Pearson Education, Inc. Figure 15.5 Membrane-Disrupting Toxins Lyse host’s cells by Making protein channels in the plasma membrane – Leukocidins – Hemolysins – Streptolysins Disrupting phospholipid bilayer Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Exotoxin Source Relation to microbe Chemistry Mostly Gram + By-products of growing cell Protein Fever? No Neutralized by antitoxin? Yes LD50 Copyright © 2010 Pearson Education, Inc. 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 + Copyright © 2010 Pearson Education, Inc. Endotoxins Source Relation to Microbe Chemistry Gram Outer membrane Lipid A Fever? Yes Neutralized by Antitoxin? No LD50 Copyright © 2010 Pearson Education, Inc. Relatively large Figure 15.4b Endotoxins and the Pyrogenic Response Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. 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. Copyright © 2010 Pearson Education, Inc. 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? Copyright © 2010 Pearson Education, Inc. 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) Copyright © 2010 Pearson Education, Inc. Cytopathic Effects of Viruses Copyright © 2010 Pearson Education, Inc. Figure 15.7 Cytopathic Effects of Viruses Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Pathogenic Properties of Fungi Ergot toxin – effects similar to LSD Claviceps Aflatoxin – potentially carcinogenic Aspergillus Mycotoxins Neurotoxins: Phalloidin, amanitin Amanita Copyright © 2010 Pearson Education, Inc. Pathogenic Properties of Protozoa Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by Growing in phagocytes Antigenic variation Copyright © 2010 Pearson Education, Inc. Pathogenic Properties of Helminths Use host tissue Presence of parasite interferes with host function Parasite's metabolic waste can cause symptoms Copyright © 2010 Pearson Education, Inc. Pathogenic Properties of Algae Paralytic shellfish poisoning Dinoflagellates Saxitoxin; type of neurotoxin Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc.