Microbial Mechanisms of Pathogenicity Chapter 15 Microbial Mechanisms of Pathogenicity

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?

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

Mechanisms of Pathogenicity Figure 15.9

Mechanisms of Pathogenicity Pathogenicity: The ability to cause disease Virulence: The extent of pathogenicity

Portals of Entry Mucous membranes Skin Respiratory tract, GI tract, Genitourinary tract Skin Parenteral route (piercing skin or mucous membranes) Every microbe has a preferred portal of entry!

Numbers of Invading Microbes ID50: Infectious dose for 50% of the test population LD50: Lethal dose for 50% of the test population

Bacillus anthracis Portal of Entry ID50 LD50 Skin 10–50 endospores Unknown, but rarely lethal Inhalation 10,000–20,000 endospores Unknown, but high mortality rate Ingestion 250,000–1,000,000 endospores Unknown and rare, but high mortality rate

Toxins Portal of Entry ID50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg Staphylococcal enterotoxin 1350 ng/kg

Adherence Adhesins/ligands bind to receptors on host cells Glycocalyx: Streptococcus mutans Fimbriae: Escherichia coli M protein: Streptococcus pyogenes Form biofilms

Adherence Figure 15.1

Adherence Figure 15.1

Adherence 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

Virulence Contributors Capsules Cell Wall Components Enzymes Membrane Ruffling Antigenic Variation Penetration of Cytoskeleton

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: Coagulates fibrinogen Kinases: Digest fibrin clots Hyaluronidase: Hydrolyzes hyaluronic acid Collagenase: Hydrolyzes collagen IgA proteases: Destroy IgA antibodies

Antigenic Variation Alter surface proteins ANIMATION Virulence Factors: Hiding from Host Defenses Figure 22.16

Membrane Ruffling 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 Figure 15.2

How Pathogens Damage Host Using the host’s nutrients / Metabolizing the host Direct Damage v. toxin damage

Using the Host’s Nutrients: Siderophores Use host’s iron Figure 15.3

Direct Damage Disrupt host cell function Produce waste products Toxins ANIMATION Virulence Factors: Penetrating Host Tissues ANIMATION Virulence Factors: Enteric Pathogens

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

Exotoxins and Endotoxins Figure 15.4

Exotoxins Specific for a structure or function in host cell ANIMATION Virulence Factors: Exotoxins Figure 15.4a

The Action of an A-B Exotoxin Figure 15.5

Membrane-Disrupting Toxins Lyse host’s cells by Making protein channels in the plasma membrane Leukocidins Hemolysins Streptolysins Disrupting phospholipid bilayer

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

By-products of growing cell Exotoxin Source Mostly Gram + Relation to microbe By-products of growing cell Chemistry Protein Fever? No Neutralized by antitoxin? Yes LD50 Small Figure 15.4a

Exotoxins & Lysogenic Conversion Cells only produce toxin when infected by bacteriophage; bacteriophage induces phenotypic change Exotoxin Lysogeny Corynebacterium diphtheriae A-B toxin + Streptococcus pyogenes Membrane-disrupting erythrogenic toxin Clostridium botulinum A-B toxin; neurotoxin C. tetani Vibrio cholerae A-B toxin; enterotoxin Staphylococcus aureus Superantigen

Endotoxins Source Gram Relation to Microbe Outer membrane Chemistry Lipid A Fever? Yes Neutralized by Antitoxin? No LD50 Relatively large Figure 15.4b

Endotoxins and the Pyrogenic Response 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

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.

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?

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)

Cytopathic Effects of Viruses Figure 15.7

Cytopathic Effects of Viruses 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

Pathogenic Properties of Fungi Ergot toxin – effects similar to LSD Claviceps Aflatoxin – potentially carcinogenic 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 Saxitoxin; type of neurotoxin Figure 27.13

Portals of Exit Respiratory tract Gastrointestinal tract Coughing and sneezing Gastrointestinal tract Feces and saliva Genitourinary tract Urine and vaginal secretions Skin Blood Biting arthropods and needles or syringes