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Ch 15 Microbial Mechanisms of Pathogenicity
Copyright © 2010 Pearson Education, Inc. LEARNING OBJECTIVES 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, kinases, 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, membrane- disrupting toxins, and superantigens Classify diphtheria toxin, erythrogenic toxin, botulinum toxin, tetanus toxin, Vibrio enterotoxin, and staphylococcal enterotoxin
Copyright © 2010 Pearson Education, Inc. Vocabulary Pathogenicity: Ability of a pathogen to cause disease by overcoming the host defenses Virulence: Degree of pathogenicity. Attachment is step 1: Bacteria use ___________ ___________ Viruses use ___________
Copyright © 2010 Pearson Education, Inc. (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; can enter through hair follicles and sweat ducts. Parenteral Route Trauma (S. aureus, C. tetani) Arthropods (Y. pestis) Injections
Copyright © 2010 Pearson Education, Inc. Bacillus anthracis Portal of EntryID 50 Skin10–50 endospores Inhalation10,000–20,000 endospores Ingestion250,000–1,000,000 endospores Numbers of Invading Microbes Clinical and Epidemiologic Principles of Anthrax at ID 50 : Infectious dose for 50% of the test population LD 50 : Lethal dose (of a toxin) for 50% of the test population
Copyright © 2010 Pearson Education, Inc. Adhesins: surface projections on pathogen, mostly made of glycoproteins or lipoproteins. Adhere to complementary receptors on the host cells. Adhesins can be part of: Adherence Glycocalyx: e.g.Streptococcus mutans 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.
Copyright © 2010 Pearson Education, Inc. Overcoming 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 cells cytoskeleton to form a basket that carries the bacteria into the cell. ANIMATION Virulence Factors: Hiding from Host Defenses
Copyright © 2010 Pearson Education, Inc. Invasins Salmonella alters host actin to enter a host cell Use actin to move from one cell to the next Listeria Penetration into the Host Cell Cytoskeleton Fig 15.2
Copyright © 2010 Pearson Education, Inc. 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 IgA protease: IgA destruction Enzymes
Copyright © 2010 Pearson Education, Inc. Enzymes Used for Penetration
How Pathogens Damage Host Cells 1.Use hosts nutrients; e.g.: Iron 2.Cause direct damage 3.Produce toxins 4.Induce hypersensitivity reaction ANIMATION Virulence Factors: Enteric Pathogens ANIMATION Virulence Factors: Penetrating Host Tissues
Copyright © 2010 Pearson Education, Inc. Toxins Exotoxins: proteins (Gram- and + bacteria can produce) Endotoxins: Gram- bacteria only. LPS, Lipid A part released upon cell death. Symptoms due to vigorous inflammation. Massive release endotoxic shock Foundation Fig 15.4 ANIMATION Virulence Factors: Exotoxins
Copyright © 2010 Pearson Education, Inc. Vocabulary related to Toxin Production Toxin: Substances that contribute to pathogenicity. Toxigenicity: Ability to produce a toxin. Toxemia: Toxoid: Antitoxin:
Copyright © 2010 Pearson Education, Inc. Exotoxins Summary Source:Gram + and Gram - Relation to microbe:By-products of growing cell Chemistry:Protein Fever?No Neutralized by antitoxin? Yes LD 50 :Small Circulate to site of activity. Affect body before immune response possible. Exotoxins with special action sites: Neuro-, and enterotoxins
Copyright © 2010 Pearson Education, Inc. Portal of EntryID 50 Botulinum (in mice)0.03 ng/kg Shiga toxin250 ng/kg Staphylococcal enterotoxin1350 ng/kg Toxin Examples Which is the least potent toxin? 1.Botulinum 2.Shiga 3.Staph
Fig 15.5 Type of Exotoxins: A-B Exotoxins
Copyright © 2010 Pearson Education, Inc. Membrane-Disrupting Toxins Lyse hosts cells by 1.Making protein channels into the plasma membrane, e.g. S. aureus 2.Disrupting phospholipid bilayer, e.g. C. perfringens Examples: Leukocidin: PMN and M destruction Hemolysin (e.g.: Streptolysin) : RBCs lysis get at ?
Copyright © 2010 Pearson Education, Inc. Superantigens Special type of Exotoxin Nonspecifically stimulate T-cells. Cause intense immune response due to release of cytokines from host cells. Fever, nausea, vomiting, diarrhea, shock, and death.
Copyright © 2010 Pearson Education, Inc. Bacterial SpeciesExotoxinLysogeny C. diphtheriaeA-B toxin+ S. pyogenes Membrane-disrupting erythrogenic toxin + C. botulinumA-B toxin; neurotoxin+ C. tetaniA-B toxin; neurotoxin V. choleraeA-B toxin; enterotoxin+ S. aureusSuperantigen+ Representative Examples of Exotoxins
Copyright © 2010 Pearson Education, Inc. 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
Copyright © 2010 Pearson Education, Inc. Source:Gram – Relation to microbe: Present in LPS of outer membrane Chemistry:Lipid A component of LPS Fever?Yes Neutralized by antitoxin? No LD 50 :Relatively large Endotoxin Summary
Copyright © 2010 Pearson Education, Inc. Inflammation Following Eye Surgery Patient did not have an infection The LAL assay of solution used in eye surgery What was the cause of the eye inflammation? What was the source? Clinical Focus, p. 440
Copyright © 2010 Pearson Education, Inc. Evasion of IS by Growing inside cells Rabies virus spikes mimic Ach HIV hides attachment site CD4 long and slender Visible effects of viral infection = Cytopathic Effects 1.cytocidal (cell death) 2.noncytocidal effects (damage but not death). Pathogenic Properties of Viruses
Copyright © 2010 Pearson Education, Inc. Pathogenic Properties of Fungi Fungal waste products may cause symptoms Chronic infections provoke allergic responses Proteases Candida, Trichophyton Capsule prevents phagocytosis Cryptococcus Fungal Toxins Ergot toxin Claviceps purpurea Aflatoxin Aspergillus flavus
Copyright © 2010 Pearson Education, Inc. 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
Copyright © 2010 Pearson Education, Inc. 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. Microbial Mechanisms of Pathogenicity - Overview Foundation Fig 15.9
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