ch 15 sp (3).ppt

Microbial Ch 15 Mechanisms of Pathogenicity  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 eff...

Microbial Ch 15 Mechanisms of Pathogenicity  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.  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 Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores Clinical and Epidemiologic Principles of Anthrax at http://www.cdc.gov/ncidod/EID/vol5no4/cieslak.htm Copyright © 2010 Pearson Education, Inc. 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  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 cell’s cytoskeleton to form a basket that carries the bacteria into the cell. Copyright © 2010 Pearson Education, Inc. 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 Fig 15.2  Listeria Copyright © 2010 Pearson Education, Inc. 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 IgA protease: IgA destruction Copyright © 2010 Pearson Education, Inc.  Enzymes Used for Penetration Copyright © 2010 Pearson Education, Inc.  How Pathogens Damage Host Cells 1. Use host’s nutrients; e.g.: Iron 2. Cause direct damage 3. Produce toxins 4. Induce hypersensitivity reaction 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 Copyright © 2010 Pearson Education, Inc. ANIMATION Virulence Factors: Exotoxins  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 Yes antitoxin? LD50: 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.  Toxin Examples Portal of Entry ID50 Botulinum (in mice) 0.03 ng/kg Shiga toxin 250 ng/kg Staphylococcal enterotoxin 1350 ng/kg Which is the least potent toxin? 1.Botulinum 2.Shiga 3.Staph Copyright © 2010 Pearson Education, Inc. Type of Exotoxins: Fig 15.5 A-B Exotoxins Fig 15.5 Membrane-Disrupting Toxins Lyse host’s 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.  Representative Examples of Exotoxins Bacterial Species Exotoxin Lysogeny C. diphtheriae A-B toxin + Membrane-disrupting S. pyogenes + erythrogenic toxin C. botulinum A-B toxin; neurotoxin + C. tetani A-B toxin; neurotoxin V. cholerae A-B toxin; enterotoxin + S. aureus Superantigen + 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. Copyright © 2010 Pearson Education, Inc. Fig 15.6  Endotoxin Summary Source: Gram – Relation to Present in LPS of outer microbe: membrane Chemistry: Lipid A component of LPS Fever? Yes Neutralized by No antitoxin? LD50: Relatively large 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? Copyright © 2010 Pearson Education, Inc. Clinical Focus, p. 440 Pathogenic Properties of Viruses 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). Copyright © 2010 Pearson Education, Inc.  Pathogenic Properties of Fungi  Fungal waste products may cause symptoms Fungal Toxins  Chronic infections provoke  Ergot toxin allergic responses  Claviceps purpurea  Proteases  Aflatoxin  Candida, Trichophyton  Aspergillus flavus  Capsule prevents phagocytosis  Cryptococcus 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 Copyright © 2010 Pearson Education, Inc.