Ch 15 Microbial Mechanisms of Pathogenicity Student Learning
Ch 15 Microbial Mechanisms of Pathogenicity
Student Learning Outcomes Identify the principal portals of entry and exit. Using examples, explain how microbes adhere to host cells. Explain how capsules and cell wall components contribute to pathogenicity. Compare the effects of coagulases, hyaluronidase, and collagenase. Describe the function of siderophores. Provide an example of direct damage, and compare this to toxin production. Contrast the nature and effects of exotoxins and endotoxins. Outline the mechanisms of action of A-B toxins and superantigens
Vocabulary Pathogenicity: Ability of a pathogen to cause disease by overcoming the host defenses Virulence: ____ of pathogenicity. Attachment via _______ is step 1: Bacteria use ___________ Viruses use ______
(Preferred) Portals of Entry Mucous membranes § Conjunctiva § Respiratory tract: Droplet inhalation of moisture and dust particles. Most common portal of entry. § GI tract: food, water, contaminated fingers § Genitourinary tract Skin § Impenetrable for most microorganisms; possible to enter through hair follicles and sweat ducts. Parenteral Route ØTrauma (S. aureus, C. tetani) ØArthropods (Y. pestis) ØInjections
Numbers of Invading Microbes ID 50: __________________ LD 50: __________________ Bacillus anthracis Portal of Entry ID 50 Skin 10– 50 endospores Inhalation 10, 000– 20, 000 endospores Ingestion 250, 000– 1, 000 endospores at http: //www. cdc. gov/ncidod/EID/vol 5 no 4/cieslak. htm Clinical and Epidemiologic Principles of Anthrax
What is the LD 50 for the bacterial toxin tested in the example below?
Adherence Adhesins: surface projections on pathogen, mostly made of glycoproteins or lipoproteins. Adhere to complementary receptors on the host cells. Adhesins can be part of: § Glycocalyx: e. g. Streptococcus mutans Fig 15. 1 § Fimbriae (also pili and flagella): e. g. E. coli Host cell receptors are most commonly sugars (e. g. mannose for E. coli Biofilms provide attachment and resistance to antimicrobial agents.
Penetration of Host Defenses § Capsules: inhibition or prevention of _______ § Cell Wall Proteins: e. g. M protein of S. pyogenes § Antigenic Variation: Avoidance of IS, e. g. Trypanosoma Neisseria § Penetration into the Host Cell Cytoskeleton: Salmonella and E. coli produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket that carries the bacteria into the cell. See Fig 15. 2 MASTERING ANIMATION Virulence Factors: Hiding from Host Defenses
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 Fig 15. 2
Enzymes Coagulase: Blood clot formation. Protection from phagocytosis (virulent S. aureus) Kinase: blood clot dissolve (e. g. : streptokinase) Hyaluronidase: (Spreading factor) Digestion of “intercellular cement” tissue penetration Collagenase: Collagen hydrolysis Ig. A protease: Ig. A destruction
Enzymes Used for Penetration
How Pathogens Damage Host Cells 1. Direct damage 2. Use host’s nutrients; e. g. : Iron 3. Produce toxins 4. Induce hypersensitivity reaction Mastering: Virulence Factors – Penetrating Host Tissues & Enteric Pathogens
Toxins Exotoxins: proteins (Gram- and + bacteria can produce) Endotoxins: Gram- bacteria Foundation Fig 15. 4 only. LPS, Lipid A part released upon cell death. Symptoms due to vigorous inflammation. Massive release endotoxic shock Mastering: Virulence Factors – Exotoxins
Vocabulary related to Toxin Production § Toxin: Substances that contribute to pathogenicity. § Toxigenicity: Ability to produce a toxin. § Toxemia: § Toxoid: § Antitoxin:
Exotoxins Summary Source: Relation to microbe: Chemistry: Fever? Neutralized by antitoxin? LD 50: Gram + and Gram By-products of growing cell _____ No _____ Small Circulate to site of activity. Affect body before immune response possible. Exotoxins with special action sites: Neuro-, and enterotoxins
Toxin Examples Portal of Entry Botulinum (in mice) Staphylococcal enterotoxin Shiga toxin LD 50 0. 03 ng/kg 1. 35 g/kg 250 ng/kg Which is the least potent toxin? A. Botulinum B. Shiga C. Staph
Type of Exotoxins: A-B Exotoxins Fig 15. 5
Superantigens as Toxins Special type of Exotoxin Nonspecifically stimulate T-cells. Intense immune response due to release of cytokines. Fever, nausea, vomiting, diarrhea, shock, and death.
Representative Examples of Exotoxins Bacterial Species Exotoxin C. diphtheriae A-B toxin S. pyogenes Membrane-disrupting erythrogenic toxin C. botulinum A-B toxin; neurotoxin C. tetani A-B toxin; neurotoxin V. cholerae A-B toxin; enterotoxin S. aureus Superantigen
Endotoxins § Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins. § Endotoxins cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure). § TNF release also allows bacteria to cross BBB. § The LAL assay (Limulus amoebocyte lysate) is used to detect endotoxins in drugs and on medical devices. Fig 15. 6
Endotoxin Summary Source: Relation to microbe: Chemistry: Gram – Present in LPS of outer membrane ___________ Fever? Neutralized by antitoxin? Yes LD 50: Relatively large _______
Pathogenic Properties of Viruses Evasion of IS by § Growing inside cells § Rabies virus spikes mimic ACh § HIV hides attachment site CD 4 long and slender Visible effects of viral infection = Cytopathic Effects 1. cytocidal (cell death) 2. noncytocidal effects (damage but not death).
Pathogenic Properties of Fungi § Fungal waste products may cause symptoms Fungal Toxins § Chronic infections provoke allergic responses § Ergot toxin § Proteases § Aflatoxin § Candida, Trichophyton § Capsule prevents phagocytosis § Cryptococcus § Claviceps purpurea § Aspergillus flavus
Pathogenic Properties of Protozoa & Helminths § Presence of protozoa § Protozoan waste products may cause symptoms § Avoid host defenses by § Growing in phagocytes § Antigenic variation § Presence of helminths interferes with host function § Helminths metabolic waste can cause symptoms Wuchereria bancrofti
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
Microbial Mechanisms of Pathogenicity Overview Foundation Fig 15. 9
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