Bacterial pathogenesis


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Bacterial pathogenesis

  2. 2. Why we do not get ill? (i) the entire invading population is killed by phagocytic cells, such as neutrophils, or circulating bacteriocidal compounds, such as complement (ii) the density of bacteria traversing the integument is collectively too low to condition the tissue to allow their population to grow or (iii) the mutations or phase shifts required to get across the mucosa or survive in the blood do not occur. It is complex and strong stochasticA.S. HOZA
  3. 3. Introduction A pathogen is a microorganism that is able to cause disease in a plant, animal or insect. Pathogenicity is the ability to produce disease in a host organism. Microbes express their pathogenicity by means of their virulence, a term which refers to the degree of pathogenicity of the microbe. Determinants of virulence of a pathogen are any of its genetic or biochemical or structural features that enable it to produce disease in a host.A.S. HOZA
  4. 4. Introduction The relationship between a host and a pathogen is dynamic, since each modifies the activities and functions of the other. The outcome of such a relationship depends on:  the virulence of the pathogen and the relative degree of resistance or susceptibility of the host, mainly due to the effectiveness of the host defense mechanisms.A.S. HOZA
  5. 5. Animals and microbes  Normal flora (beneficial or ignored):  GI track, skin, upper respiratory track  Virulent bacteria (actively cause disease):  pathogenic islands  Opportunistic bacteria (when host with underline problem):  Pseudomonas aeruginosa: cystic fibrosis/ burn  TB, Kaposi’s sarcoma (herpesvirus): AIDSA.S. HOZA
  6. 6. Mechanisms of Bacterial Pathogenicity 1. Invasiveness: the ability to invade tissues.  encompasses mechanisms for  colonization (adherence and initial multiplication),  production of extracellular substances which facilitate invasion (invasins) and  ability to bypass or overcome host defense mechanisms.A.S. HOZA
  7. 7. Mechanisms of Bacterial Pathogenicity2. Toxigenesis: ability to produce toxins. Bacteria may produce two types of toxins: i. exotoxins and ii. endotoxins.  Exotoxins are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth.  Endotoxins are cell-associated substance. (classic sense, endotoxin refers to the lipopolysaccharide component of the outer membrane of Gram-negative bacteria).A.S. HOZA
  8. 8. Mechanisms of Bacterial Pathogenicity  Endotoxins may be released from growing bacterial cells and cells that are lysed as a result of effective host defense (e.g. lysozyme) or the activities of certain antibiotics (e.g. penicillins and cephalosporins).  Hence, bacterial toxins, both soluble and cell-associated, may be transported by blood and lymph and cause cytotoxic effects at tissue sites  Some bacterial toxins may also act at the site of colonization and play a role in invasion.A.S. HOZA
  9. 9. Animals and microbes  Normal flora (beneficial or ignored):  GI track, skin, upper respiratory track  Virulent bacteria (actively cause disease):  pathogenic islands  Opportunistic bacteria (when host with underline problem):  Pseudomonas aeruginosa: cystic fibrosis/ burn  TB, Kaposi’s sarcoma (herpesvirus): AIDSA.S. HOZA
  10. 10. Big person in microbiology Robert Koch,1843-1910, Germany Koch’s postulates: 1. suspected pathogen must be present 2. pathogen must be isolated and grown in pure culture 3. cultured pathogen must cause the disease 4. Same pathogen must be re-isolated from the subjectA.S. HOZA
  11. 11. Bacterial pathogenesis  Infection/entry  Virulence factors  Pathogenesis  Escape of immune surveillanceA.S. HOZA
  12. 12. Infection/entry  Ingestion (fecal-oral)  Inhalation (respiratory)  Trauma (e.g burn)  Arthropod bite (zoonoses: mosquito, flea, tick, Tsetse fly)  Sexual transmission  Iatrogenic (needle stick, blood transfusion)  Maternal-neonatalA.S. HOZA
  13. 13. Bacteria, virus, fungi  Ingestion: Salmonella, Shigella, Vibrio, Clostridium etc..  Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..  Trauma: Clostridium tetani  Arthropod bite: Rickettsia, Yersinia pestis, etc.  Sexual transmission: Neisseria gonorrboeae, HIV, chlamydia, etc  Needle stick: Staphylococcus, HIV, HBV  Maternal-neonatal: HIV, HBV, Neisseria, etc.A.S. HOZA
  14. 14. Modes of infectious disease transmission Contact transmission Direct contact (person-to-person): syphilis, gonorrhear, herpes Indirect contact (fomites): enterovirus infection, measles Droplet (less than 1 meter): whooping cough, strep throat Vehicle transmission Airborne: influenza, tuberculoses, chickenpox Water-borne (fecal-oral infection): cholera, diarrhea Food-borne: hepatitis, food poisoning, typhoid fever Vector transmission Biological vectors: malaria, plaque, yellow fever Mechanical vectors: E. coli diarrhea, salmonellosisA.S. HOZA
  15. 15. Extracellular versus Intracellular Parasitism  Extracellular parasites  destroyed when phagocytosed.  damaging tissues as they remain outside cells.  inducing the production of opsonizing antibodies, they usually produce acute diseases of relatively short duration.  Intracellular parasites  can multiply within phagocytes.  frequently cause chronic disease.A.S. HOZA
  16. 16. The environment in a cell  Cytosol: pH=7  Phagosome: pH=6  Phagolysosome: pH=5 Adapted from: HOZA
  17. 17. Barrier systems Host cell Taken up by Inhibitory Mycobacterium membrane phagocyte molecule and resist killing Production Degrade IgA protease Streptococcus Of antibody antibody Antimicrobial Activate T cells Superantigen Staphylococcus cell-mediated non-specifically response and Productively Antimicrobial Vary presenting Switch on Borrelia immune microbial production of response antigen different antigens Genetic Streptococcus recombinationA.S. HOZA
  18. 18. Virulence factors Factors enhancing the ability of bacteria to cause disease Example: Pseudomonas aeruginosa  Adhesins: attachment  Alginate production: mucoid layer  Exotoxin A: inhibits host protein synthesis  Exoenzyme S: interferes with phagocytic killing  Elastolytic activity: degrades elastin  Phospholipase C: damages tissue  Pyocyanin: damages tissue by ROS  Antibiotic resistance: complicates therapyA.S. HOZA
  19. 19. Pathogenic action of bacteria  Tissue destruction: flesh-eating bacteria: Clostridium perfrigens  Obstruction: Cytic fibrosis  Toxins: bacterial components that directly harm tissue or trigger disease symptoms  Endotoxin: lipopolysaccharides  Exotoxin: A-B toxins  Immunopathogenesis  Excess immune responses  AutoimmunityA.S. HOZA
  20. 20. 2. Endotoxins: heat stableA.S. HOZA
  21. 21. Endotoxin: lipopolysaccharide IL-1 Pseudomonas aeruginosa TNF FeverDisseminated intravascular coagulation Septic shock death A.S. HOZA
  22. 22. Superantigens Secreted proteins (exotoxins) that exhibit highly potent lymphocyte- transforming (mitogenic) activity directed towards T lymphocytes. Polyclonal T cell activation Aberrant cytokines, Antigen /MHC-1 cell death Specific T cell activation Anti-microbes immunityA.S. HOZA
  23. 23. Known and suspected association of superantigens with animal diseases Autoimmune diseases Lyme disease Multiple sclerosis Acute diseases Food poisoning: Staph infections StreptococalA.S. HOZA
  24. 24. EVASION STRATEGIES (1) Defence Microbial strategy Mechanism Example Wash-out Bind to cell Adhesins Neisseria Inhibit ciliary Ciliotoxic/ Bordetella activity Ciliostatic Streptococcus molecule Disrupt Leucocidins Staphylococcus Chemotaxis Ingestion cytotoxic and killing by phagocyte Inhibit Capsule Streptococcus phagocytosis Inhibit lysosomal Inhibitory Mycobacterium fusion molecule Multiply Unknown ListeriaA.S. HOZA
  25. 25. EVASION STRATEGIES (2) Defence Microbial strategy Mechanism Example Restrict Fe- Compete Siderophore Mycobacterium Lactoferrin Escherichia Transferrin Interfere with Fully sialylated Neisseria Activate alternative pathway surface complement Inactivate Elastase Pseudomonas Antigen projects Activation occurs Gram-negatives beyond surface at the wrong site Interfere with C3b receptor Streptococcus complement- competition, mediated microbe and phagocytosis phagocyteA.S. HOZA