Microbial Pathogenesis

Method of pathogenesis by microorganisms

1. MICROBIAL PATHOGENECITY SAMIRA FATTAH HAMID Ph.D. Medical Bacteriology College of Health Sciences Hawler Medical University

2. Microbial Pathogenicity Pathogenicity = ability to cause disease Virulence = degree of pathogenicity

3. To cause disease a pathogen must: 1 . gain access to the host 2. adhere to host tissues 3. penetrate or evade host defenses 4. damage the host, either: - directly - accumulation of microbial wastes

4. Entry into Host A. Mucus membranes most common route for most pathogens. Entry through mucus membranes of: respiratory tract (most common) gastrointestinal tract urinary/genital tracts conjunctiva 1. Portals of Entry

5. Entry Into Host 1. Portals of Entry B. Skin some pathogens infect hair follicles and sweat glands few can colonize surface unless broken, skin is usually an impermeable barrier to microbes

6. Entry Into Host 1. Portals of Entry C. Parenteral route penetrate skin: through punctures, injections, bites, cuts, surgery, etc. most microbes must enter through their preferred portal of entry in order to cause disease. some can cause disease from many routes of entry.

7. Entry Into Host 2. Numbers of Invading Microbes likelihood of disease increases as the number of invading pathogens increases ID50 (Infectious Dose) = number of microbes required to produce infection in 50% of the population. -different ID50 for different pathogens -different ID50 for different portals of entry for the same pathogen LD50 (Lethal Dose) = amount of toxin or pathogen necessary to kill 50% of the population in a particular time frame.

8. Entry Into Host 3. Adherence Adherence = attachment to the host by the microbe at portal of entry. blocking adhesion can prevent disease pathogen has surface molecules called adhesions or ligands that bind specifically to the host surface receptors. most microbial adhesions are glycoproteins or lipoproteins located on the glycocalyx, capsule, capsid, pili, fimbriae or flagella most host receptors are typically proteins (for virus) or carbohydrates (for bacteria) in the wall or membrane of host cell

9. Entry Into Host 3. Adherence Biofilms: formed when microbes adhere to a surface that is usually moist and contains organic matter. each microbe secretes glycocalyx allowing other microbes to adhere and a large mass is formed. the biofilm is resistant to disinfectants and antibiotics (outer layer protects inner layers) problem for catheters and surgical implants.

10. Penetration of Host Defenses 1. Capsules Capsules = organized glycocalyx layer (carbohydrates) outside cell wall impairs phagocytosis: prevents engulfment and destruction by leukocytes if present, is usually required for virulence.

11. Penetration of Host Defenses 2. Cell Wall Components A. M protein of Streptococcus pyogenes : heat and acid resistant mediates attachment of bacterium to epithelial cells resists phagocytosis by leukocytes.

12. Penetration of Host Defenses 2. Cell Wall Components B. Fimbriae + Opa (membrane protein) used by Neisseria gonorrhoeae: -promote attachment and uptake by host epithelial cells and leukocytes -Neisseria then grows inside these cells. C. Mycolic acid (waxy) of Mycobacterium tuberculosis . -resist digestion by phagocytes -Mycobacterium then grows inside phagocyte

13. Penetration of Host Defenses 3. Enzymes (exoenzymes ) Coagulases: clot fibrin in blood to create protective barrier against host defenses. Kinases: dissolve clots (fibrinolysis) to allow escape from isolated wounds e.g. Streptokinase (Streptococcus pyogenes) Staphylokinase (Staphylococcus aureus) Hyaluronidase: hydrolyzes hyaluronic acid (‘glue’ that holds together connective tissues and epithelium barriers) allowing deeper invasion. e.g. Clostridium species: allows them to cause gangrene (tissue necrosis)

14. Penetration of Host Defenses 3. Enzymes (exoenzymes) Collagenase: breaks down collagen (fibrous part of connective tissue) for invasion into muscles and organs e.g. Clostridium species IgA proteases: destroy host IgA antibodies found in mucous secretions to allow adherence and passage at mucus membranes e.g. Neisseria species that infect CNS

15. Penetration of Host Defenses 4. Antigenic Variation pathogen alters its surface antigens to escape attack by antibodies and immune cells e.g.1 Neisseria gonorrhoeae has many versions of the Opa gene , it can alter which one is being expressed e.g.2 influenza virus - spike proteins can mutate and change over time and prevents antibodies from binding to it .

16. Damage to Host Cells 1. Using hosts n utrients e.g. iron required for all cells (electron transport chain: cytochromes) both host and pathogen host usually does not have free iron available (free iron leads to easy colonization by pathogens) humans bind unused iron to transport proteins: transferrin pathogens can produce siderophores ( iron carrier ) : secreted by bacteria to compete iron from host proteins, siderophore iron complex then absorbed by bacteria

17. Damage to Host Cells 2. Direct damage to colonized area growth and replication in host cells: results in host cell lysis penetration through host cells (mucosa, organs) causes damage lysis of host cells to obtain nutrients

18. Damage to Host Cells 3. Production of toxins A. Exotoxins produced inside the bacteria and either secreted or released following microbe lysis. function to destroy certain host cell parts or inhibit particular metabolic functions damage from toxin results in the particular signs or symptoms of a disease can be named for the disease, type of cell attacked or organism that produces it e.g. tetanus toxin: causes tetanus (contraction) of muscle.

19. T hree types of exotoxins: 1) A-B toxins Two parts: A is the enzyme that disrupts some cell activity B binds surface receptors to bring A into the host cell e.g. botulinum & tetanus toxin Damage to Host Cells

20. Damage to Host Cells 2) Membrane disrupting toxins cause lysis of the host cell by disrupting the plasma membrane e.g. leukocidins : make protein channels in phagocytic leukocytes e.g. hemolysins: make protein channels in RBCs ( B -hemolysis: Steptococcus pyogenes ) 3) Superantigens bacterial proteins that cause proliferation of T cells and release of cytokines excessive cytokines can cause fever, nausea, vomiting, diarrhea, shock and death (septic shock) e.g. toxic shock syndrome ( Staphylococcus ) e.g. enterotoxins: Staphylococcal food poisoning

21. Damage to Host Cells B. Endotoxins part of the outer membrane portion of the cell wall of gram negative bacteria: Lipopolysaccharide (LPS) released when dead cells lyse in blood, causes macrophages to release high levels of cytokines resulting in chills, fever, weakness, aches, small blood clots, tissue necrosis, shock and death. Sterile solutions can contain LPS: bacteria dies in sterilization but LPS is unaltered.. Due to serious consequences at very low levels of LPS, it is essential to test medical devices and solutions for endotoxin.

22. Pathogenic Properties of Virus 1. Mechani sms to evade host defenses A. Grow inside host cells to hide from immune defense B. Kill immune cells e.g. HIV – T-Helper Cells 2. Cytopathic effects = visible effects of viral infection on host cell: some effects will kill the cell, some will just change the cell A. stop DNA, RNA and/or protein synthesis e.g. Herpes virus block mitosis B. lysosomal autolysis of host cells e.g. Influenza: bronchiolar epithelium C. production of inclusion bodies (visible viral parts inside the cell) can identify a particular virus e.g. Rabies virus: Negri bodies

23. Pathogenic Properties of Virus 2. Cytopathic effects syncytium formation (neighboring cells fuse together) e.g. Varicella Zoster virus E. change in cell function e.g. Measles production of interferons by host cell (triggers host immune response) cell transformation : may activate or deliver oncogenes resulting in loss of contact inhibition (cancer) e.g. Papilloma virus

24. Eukaryotic Pathogens 1. Fungi: produce toxins causing allergies or disease e.g. chronic sinusitis (black molds)- tachybotrys : cause headaches, vomiting, mental disturbance invasive systemic mycosis in immune compromised patients e.g. Candida mycotoxins produced by mushrooms may be hallucinogenic or deadly .

25. Eukaryotic Pathogens 2. Protozoa: can grow inside host cells causing lysis e.g. Malaria ( Plasmodium ) use host cells as food source produce wastes that cause disease 3. Algae produce neurotoxic substances (poisoning) e.g. (dinoflagellates)