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  1. 1. Chapter 15: Microbial Mechanisms of pathogenicity <ul><li>Pathogen = microbe or virus able to produce disease </li></ul><ul><li>Pathogenicity = the ability of a microbe to cause disease in another organism </li></ul><ul><ul><li>Ex. The host – usually human </li></ul></ul><ul><li>Virulence = the power of an organism to cause disease </li></ul><ul><ul><li>It is the degree of pathogenicity </li></ul></ul><ul><ul><li>Virulent organisms usually produce a violent, severe disease often leading to death </li></ul></ul>
  2. 2. Chapter 15: Microbial Mechanisms of pathogenicity <ul><li>Virulence cont. </li></ul><ul><ul><li>Chickenpox, common cold viruses are pathogens not considered to be virulent </li></ul></ul><ul><ul><li>Yersinia pestis – bubonic plague, Ebola viruses – virulent pathogens </li></ul></ul><ul><li>Virulence factors = pathogen produced molecules or structures that allow the cell to invade the host or evade your immune system and may result in disease in the host </li></ul>
  3. 3. How do microbes become established in a host <ul><li>Step 1 </li></ul><ul><li>Portal of entry – how pathogens get in or onto the body </li></ul><ul><ul><li>Mucous membranes – line the conjunctiva of the eye, and the respiratory, Gastrointestinal and genital -urinary tracts </li></ul></ul><ul><ul><ul><li>Respiratory tract is easiest and most frequently used route – cold, pneumonia, TB, flu, measles, smallpox </li></ul></ul></ul>
  4. 4. How do microbes become established in a host <ul><li>Step1:Portal of entry: Mucous membranes </li></ul><ul><ul><li>Gastrointestinal tract – contacted through food, water, fingers </li></ul></ul><ul><ul><ul><li>May be destroyed by stomach acids and intestinal enzymes </li></ul></ul></ul><ul><ul><ul><li>Ex. Polio, hepatitis A, typhoid fever, amoebic dysentery, shigellosis (aka bacilliary dysentery), and cholera are transmitted through the GI tract </li></ul></ul></ul><ul><ul><ul><ul><li>Pathogens leave (Portal of exit) through the feces to find a new host </li></ul></ul></ul></ul>
  5. 5. How do microbes become established in a host <ul><li>Step 1: Portal of entry : Skin </li></ul><ul><li>Most microbes can’t penetrate unbroken skin </li></ul><ul><ul><li>Some can penetrate by entering through openings – hair follicles, sweat ducts </li></ul></ul><ul><ul><li>Fungi can grow in the keratin of the skin and infect the skin or nails </li></ul></ul><ul><ul><li>Exception to unbroken skin is hookworms </li></ul></ul>
  6. 6. How do microbes become established in a host <ul><li>Step 1: Portal of entry : Parenteral route </li></ul><ul><ul><li>Microbes enter due to trauma to the skin and mucous membranes </li></ul></ul><ul><ul><li>Ex. Injections, punctures (tetanus), bites, cuts, wounds, or surgery </li></ul></ul><ul><li>Microbes must enter your body from the preferred portal of entry to cause the disease </li></ul><ul><ul><li>Ex. Smallpox – mucous membrane of respiratory tract, thru puncture of skin = slight inflammation of skin – immunity, vaccination </li></ul></ul>
  7. 7. Portals of Entry “ Many organisms that cause one disease if they enter one body site are harmless if they enter another, e.g., various enteric urinary-tract pathogens.
  8. 8. How do microbes become established in a host <ul><li>The ability of a pathogen to establish an infection and possible disease usually depends on the infectious dose which is the # of microbes taken into the body </li></ul><ul><li>A measure of virulence is the ID50 (infectious dose) = the number of microbes it takes to infect 50% of the population </li></ul><ul><ul><li>Cutaneous anthrax ID50 = 10 endospores, inhalation anthrax ID50 = 10,000 endospores </li></ul></ul><ul><li>The potency of a toxin is the LD50 or lethal dose to kill 50 % of a population </li></ul>
  9. 9. How do microbes become established in a host <ul><li>Step 2: Adherence or attaching to the host </li></ul><ul><ul><li>Pathogens attach to host cells by adhesins which are projections on the surface of the bacterium that adhere to complimentary receptors on the host cells </li></ul></ul><ul><ul><li>Adhesions are associated with fimbriae, glycocalyx, flagella </li></ul></ul><ul><ul><li>Parasitic worms use hooks, barbs, suckers </li></ul></ul>
  10. 10. How do microbes become established in a host <ul><li>Step 2: Adherence </li></ul><ul><li>Adherence is followed by colonization of the tissue and may involve invasion of the cells </li></ul><ul><ul><li>Ex. Biofilms – microbes secrete a glycocalyx that aids in surface attachment and to each other </li></ul></ul><ul><ul><ul><li>This allows them to share nutrients, and they are protected from antimicrobials and your immune system ex. Diphtheria – Corynebacterium diphtheriae </li></ul></ul></ul>
  11. 11. Adhesion to Host Tissues <ul><li>For most pathogens, cells must adhere to tissues (and then colonize) before infection can take place, even if ultimately damage results from invasion or exotoxin production. </li></ul><ul><li>Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae. </li></ul><ul><li>Alternatively, adhesins can consist of glycocalyx. </li></ul>
  12. 12. Step 3: Penetrating and surviving host defenses <ul><li>Capsules – aid in resistance to phagocytosis </li></ul><ul><ul><li>Streptococcus pneumoniae causes pneumococcal pneumonia – some strains have capsules and are therefore virulent and produce disease and some strains don’t have capsules and are avirulent and don’t cause disease </li></ul></ul>
  13. 13. Avoidance of Phagocytosis Capsules are Involved in avoidance of phagocyte-mediated recognition and attachment.
  14. 14. Step 3: Penetrating and surviving host defenses <ul><li>Cell wall components – aid in resisting phagocytosis and in adherence of microbes </li></ul><ul><ul><li>Waxes in cell wall – Mycobacterium tuberculosis resist digestion by macrophages </li></ul></ul><ul><ul><li>M protein produced by Streptococcus pyogenes aids in attachment to epithelial cells and resistance to phagocytosis by WBCs </li></ul></ul>
  15. 15. Step 3: Penetrating and surviving host defenses <ul><li>Enzymes – extracellular enzymes are able to lyse cells, dissolve the material between cells and form or dissolve blood clots </li></ul><ul><ul><li>Coagulases – enzymes produced by some Staphylococcus – converts fibrinogen to fibrin which causes clotting – the clots protect against phagocytosis </li></ul></ul>
  16. 16. Step 3: Penetrating and surviving host defenses <ul><ul><li>Kinases – Staphylococcus and Streptococcus – digests the fibrin thus dissolving the clots formed by the body to isolate the infection </li></ul></ul><ul><ul><ul><li>Streptokinase – used to remove some blood clots due to heart attack </li></ul></ul></ul><ul><ul><li>Hyaluronidase – Streptococcus , Staphylococcus, Clostridium – digests hyaluronic acid of connective tissue </li></ul></ul>
  17. 17. Step 3: Penetrating and surviving host defenses <ul><ul><li>Collagenase – Clostridium sp. – dissolves collagen framework of muscles – aids in the spread of gas gangrene </li></ul></ul><ul><ul><li>IgA proteases – destroys host’s defense IgA antibodies </li></ul></ul><ul><ul><li>Antigenic variation – microbes are able to change their surface antigens ( causes Ab formation) </li></ul></ul><ul><ul><li>- the immune system recognizes antigens (pathogens) and produces Abs specific for that Ag </li></ul></ul>
  18. 18. How Pathogens cause disease or damage <ul><li>Using the hosts nutrients – pathogens need iron to grow </li></ul><ul><ul><li>Iron in the host’s cell is tightly bound to iron transport proteins such as hemoglobin </li></ul></ul><ul><ul><li>Some microbes secrete proteins called siderophores which take the iron away from the iron transport proteins and form iron – siderophore complexes. These complexes bind with siderophores receptors on the bacterial surface where the iron is brought into the bacterium either as the whole complex or free iron </li></ul></ul><ul><ul><li>Cell lysis caused by pathogens can also release iron </li></ul></ul>
  19. 19. How Pathogens cause disease or damage <ul><li>Toxins – are poisonous substances produced by some microbes. If toxins are found in the blood = toxemia </li></ul><ul><li>Exotoxins are proteins usually secreted by Gram + bacteria </li></ul><ul><ul><li>They are among the most lethal substances known </li></ul></ul><ul><ul><li>They are specific to a cell type ex. Neurotoxin </li></ul></ul>
  20. 20. How Pathogens cause disease or damage <ul><li>Exotoxins cont. </li></ul><ul><ul><li>The body can produce Abs called antitoxins that provide immunity to exotoxins </li></ul></ul><ul><ul><li>Toxoids are altered exotoxins that allow the host immune system to produce antitoxins without causing any side effects </li></ul></ul><ul><ul><ul><li>Can be vaccines ex. Diphtheria, tetanus </li></ul></ul></ul>
  21. 21. How Pathogens cause disease or damage <ul><li>Types of exotoxins </li></ul><ul><ul><li>A-B toxins – most are exotoxins, consists of 2 parts </li></ul></ul><ul><ul><ul><li>A is the active part that inhibits protein synthesis and kills the host cell </li></ul></ul></ul><ul><ul><ul><li>Part B is the binding part and binds to host cell </li></ul></ul></ul><ul><ul><li>Membrane disrupting toxins – cause lysis of host cells by disrupting their plasma membranes </li></ul></ul><ul><ul><ul><li>Leukocidins – white blood cell killers </li></ul></ul></ul><ul><ul><ul><li>Hemolysins – target red blood cells </li></ul></ul></ul>
  22. 22. How Pathogens cause disease or damage <ul><li>Types of exotoxins cont. </li></ul><ul><ul><li>Superantigens – provoke an intense immune response </li></ul></ul><ul><ul><ul><li>Stimulate the proliferation of T cells which in turn release large amounts of cytokines </li></ul></ul></ul><ul><ul><ul><li>Cytokines are small proteins that regulate immune responses and in high concentrations can cause many sxs – fever, nausea, vomiting, diarrhea, shock and even death </li></ul></ul></ul>
  23. 23. How Pathogens cause disease or damage <ul><li>Some exotoxins </li></ul><ul><ul><li>Diphtheria toxin – Corynebacterium diphtheriae – A-B toxin, bacteria has to be infected by lysogenic phage (prophage) carrying the tox gene </li></ul></ul><ul><ul><li>Erythrogenic toxin- Streptococcus pyogenes –is a superantigen that damages plasma membranes of capillaries under the skin and produces red skin rash ex. Scarlet fever </li></ul></ul>
  24. 24. How Pathogens cause disease or damage <ul><li>Some exotoxins cont. </li></ul><ul><ul><li>Botulinum toxin – Clostridium botulinum – </li></ul></ul><ul><ul><li>A-B neurotoxin that causes flaccid paralysis when ingested </li></ul></ul><ul><ul><li>-- Tetanus toxin – Clostridium tetani – A-B neurotoxin aka tetanospasmin which blocks the relaxation pathway of muscle control causing spasmodic contraction = tetanus </li></ul></ul><ul><ul><li>ex. Lockjaw-mouth, opisthotonos – back ms </li></ul></ul><ul><ul><li>pg.648 fig. 22.6 </li></ul></ul>
  25. 25. How Pathogens cause disease or damage <ul><li>Some exotoxins cont </li></ul><ul><ul><li>Vibrio enterotoxin – Vibrio cholerae –A-B enterotoxin (aka cholera toxin) that causes the release of large amounts of fluids and electrolytes (ions) that result in severe diarrhea ex. Cholera </li></ul></ul><ul><ul><li>Staphylococcus enterotoxin – S. aureus – superantigen that affects the intestines the same way as cholera toxin </li></ul></ul>
  26. 26. How Pathogens cause disease or damage <ul><li>Endotoxins = lipid A which is the lipid portion of LPS (outer membrane) of G- cell wall </li></ul><ul><ul><li>Not secreted but is released upon death and lysis of the bacteria or during multiplication of bacteria </li></ul></ul><ul><ul><li>They stimulate macrophages to release large amounts of cytokines which are toxic at high concentrations </li></ul></ul><ul><ul><li>Lab test for endotoxins = Limulus amoebocyte lysate (LAL) assay </li></ul></ul><ul><ul><ul><li>Uses WBCs (amoebocytes) of horseshoe crab ( Limulus polyphemus ) which lyse if endotoxins are present releasing a clotting protein </li></ul></ul></ul><ul><ul><ul><li>Draw chart </li></ul></ul></ul>
  27. 27. Pathogenic Properties of Viruses <ul><li>Cytopathic Effects (CPE) = visible damage to host cell </li></ul><ul><ul><li>Cytocidal effects kill the cell </li></ul></ul><ul><ul><li>Noncytocidal effects damage cell – not lethal </li></ul></ul><ul><li>A virus can produce one or more of the following CPE </li></ul><ul><ul><li>Stops the synthesis of macromolecules </li></ul></ul><ul><ul><li>Cause cell’s lysosomes to release their enzymes and lyse themselves </li></ul></ul>
  28. 28. <ul><li>CPE cont. pg 466 </li></ul><ul><ul><li>Inclusion bodies = granules found in the cytoplasm (rabies virus) or nucleus (herpes virus) if some infected cells </li></ul></ul><ul><ul><li>Syncytium = adjacent infected cells fuse to form a multinucleated cell </li></ul></ul><ul><ul><li>Change in fx but otherwise no visible change ex. Decreased hormone production </li></ul></ul><ul><ul><li>Cell produces interferon which protects neighboring, uninfected cells from the virus </li></ul></ul>
  29. 29. Pathogenic Properties of Viruses <ul><li>CPE cont. </li></ul><ul><ul><li>Antigenic changes on the surface of infected cells that target the cells for destruction by the immune system </li></ul></ul><ul><ul><li>Chromosomal changes in the host cell, oncogenes may be activated </li></ul></ul><ul><ul><li>Cancer causing viruses transform host cells resulting in abnormal cell shape and a loss of contact inhibition which causes unregulated cell growth </li></ul></ul>
  30. 30. Pathogenic properties of fungi, protozoa, helminths and algae <ul><li>Protozoa and helminths grow on host tissues causing cellular damage </li></ul><ul><ul><li>Their waste products may contribute to sxs of disease </li></ul></ul><ul><li>Algae (dinoflagellates) produce neurotoxins called saxitoxin and people become ill after eating mollusks that feed on the algae </li></ul>
  31. 31. Pathogenic properties of fungi, protozoa, helminths and algae <ul><li>The toxin ergot is associated with some fungi and cause ergotism which can result in LSD type hallucinations </li></ul><ul><ul><li>Ergot is contained in resistant mycelia called sclerotia in Claviceps purpurea – fungi that grow on grains </li></ul></ul><ul><ul><li>Ergot can constrict blood capillaries and cause gangrene in extremities </li></ul></ul>
  32. 32. Pathogenic properties of fungi, protozoa, helminths and algae <ul><li>Aflatoxin is produced by the mold Aspergillus flavus and can cause cancer in the liver of animals </li></ul><ul><li>Amanita phalloides (deathcap) is a toxic mushroom which contains the mycotoxins phalloidin and amanitin. </li></ul><ul><ul><li>These neurotoxins are so potent that ingestion may cause death </li></ul></ul>
  33. 33. Portals of exit <ul><li>To complete the cycle of infectious disease and to allow transmission to new hosts, pathogens require a portal of exit </li></ul><ul><li>In some cases the portal of exit relates to the area of the body infected </li></ul><ul><li>Infections of the respiratory tract pathogens exit through the nose (sneezing) or mouth (coughing) </li></ul><ul><li>Pathogens of GI tract exit – saliva, feces </li></ul><ul><li>Pathogens of genitourinary tract exit - secretions </li></ul>