Microbial Mechanisms of Pathogenesis
Pathogenesis <ul><li>The word comes from the  Greek   pathos , &quot;disease&quot;, and  genesis , creation.  </li></ul><u...
Pathogenicity -  Ability to cause disease Virulence  -  Degree of  pathogenicity <ul><li>Many properties that determine a ...
Portals of Entry <ul><li>1. Mucus Membranes </li></ul><ul><li>2. Skin </li></ul><ul><li>3. Parenteral </li></ul>
1. Mucus Membranes <ul><li>A. Respiratory Tract </li></ul><ul><li>Sticky mucous secretion </li></ul><ul><li>Muco polysachh...
Common Diseases contracted via the Respiratory Tract <ul><li>Common  cold </li></ul><ul><li>Flu </li></ul><ul><li>Tubercul...
Mucus Membranes <ul><li>B. Gastrointestinal Tract </li></ul><ul><ul><li>Microbes gain entrance thru contaminated food & wa...
Common diseases contracted via the G.I. Tract   <ul><li>Salmonellosis </li></ul><ul><ul><li>Salmonella sp. </li></ul></ul>...
Fecal - Oral Diseases <ul><li>These pathogens enter the G.I. Tract at one end and exit at the other end. </li></ul><ul><li...
Mucus Membranes of the Genitourinary System  Acidic urine Vaginal secretion-  Acidic due to fermentation of glycogen by la...
Mucus Membranes <ul><li>D. Conjunctiva – </li></ul><ul><li>Lacrymal secretion </li></ul><ul><li>Lysozyme </li></ul><ul><li...
2.  Skin <ul><li>Skin - the largest organ of the body.  </li></ul><ul><li>Sebaceous secretion-containing fatty acids </li>...
3. Parentarel <ul><li>Microorganisms are  deposited  into the tissues below the skin or mucus membranes </li></ul><ul><li>...
Number of Invading Microbes <ul><li>LD 50  - Lethal Dose of a microbes toxin that will kill 50% of experimentally inoculat...
How do Bacterial Pathogens penetrate Host Defenses? 1. Adherence  -  almost all pathogens have a means to attach to host t...
How Bacterial Pathogens Penetrate Host Defenses <ul><li>1. Adherence </li></ul><ul><li>2. Capsule </li></ul><ul><li>3. Enz...
Adhesins and ligands are usually on Fimbriae <ul><li>Neisseria gonorrhoeae </li></ul><ul><li>ETEC  (Entertoxigenic E. coli...
2. Capsules <ul><li>Prevent phagocytosis </li></ul><ul><li>Attachment </li></ul><ul><li>Streptococcus pneumoniae </li></ul...
3. Enzymes <ul><li>Many pathogens secrete enzymes that contribute to their pathogenicity </li></ul>
A. Leukocidins <ul><li>Attack certain types of WBC’s </li></ul><ul><li>1. Kills WBC’s which prevents phagocytosis </li></u...
B. Hemolysins -  cause the lysis of RBC’s Streptococci
1. Alpha Hemolytic Streptococci  -  secrete hemolysins that cause the incomplete lysis or RBC’s
2. Beta Hemolytic Streptococci   - Secrete hemolysins that cause the complete lysis of RBC’s
C. Coagulase -  cause blood to coagulate <ul><li>Blood clots protect bacteria from phagocytosis from WBC’s and other host ...
D. Kinases -  enzymes that dissolve blood clots <ul><li>1. Streptokinase -  Streptococci </li></ul><ul><li>2. Staphylokina...
E. Hyaluronidase <ul><li>Breaks down Hyaluronic acid  (found in connective tissues) </li></ul><ul><li>“Spreading Factor” <...
F. Collagenase <ul><li>Breaks down collagen  (found in many connective tissues) </li></ul><ul><li>Clostridium perfringens ...
G. Necrotizing Factor - Causes death (necrosis) to tissue cells “ Flesh Eating Bacteria”
Bacterial Toxins <ul><li>Poisonous substances produced by microorganisms </li></ul><ul><li>Toxins -  primary factor  - pat...
Types of Toxins <ul><li>1. Exotoxins </li></ul><ul><ul><li>Exotoxins are generated by the bacteria and actively secreted  ...
Exotoxins <ul><li>Mostly seen in Gram (+) Bacteria </li></ul><ul><li>Heat labile, can be inactivated by heating at 60-80  ...
Types of Exotoxins  <ul><li>1. Cytotoxins </li></ul><ul><ul><li>Kill cells-  shigella, vibrio </li></ul></ul><ul><li>2. Ne...
Response to Toxins <ul><li>If exposed to exotoxins:  antibodies against the toxin  ( antitoxins ) </li></ul><ul><li>Exotox...
Endotoxins  <ul><li>Part of the Gram (-) Bacterial cell wall. </li></ul><ul><li>Biological activity or toxicity of endotox...
Bacteriocin <ul><li>Bacteriocins were first discovered by A. Gratia in 1925. </li></ul><ul><li>He called his first discove...
<ul><li>Classification: </li></ul><ul><li>Class I: Small peptide inhibitors . </li></ul><ul><li>Class II: Small heat-stabl...
<ul><li>Medical significance  </li></ul><ul><li>Bacteriocins are of interest in medicine because they are made by non-path...
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Mechanism Of Pathogenecity

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Mechanism Of Pathogenecity

  1. 1. Microbial Mechanisms of Pathogenesis
  2. 2. Pathogenesis <ul><li>The word comes from the Greek pathos , &quot;disease&quot;, and genesis , creation. </li></ul><ul><li>The term pathogenesis means step by step development of a disease. </li></ul><ul><li>The chain of events leading to that disease due to a series of changes in the structure and /or function of a cell/tissue/organ. </li></ul><ul><li>Caused by a microbial, chemical or physical agent. </li></ul>
  3. 3. Pathogenicity - Ability to cause disease Virulence - Degree of pathogenicity <ul><li>Many properties that determine a microbe’s pathogenicity or virulence are unclear or unknown </li></ul><ul><li>But, when a microbe overpowers the hosts defenses, disease results! </li></ul>
  4. 4. Portals of Entry <ul><li>1. Mucus Membranes </li></ul><ul><li>2. Skin </li></ul><ul><li>3. Parenteral </li></ul>
  5. 5. 1. Mucus Membranes <ul><li>A. Respiratory Tract </li></ul><ul><li>Sticky mucous secretion </li></ul><ul><li>Muco polysachharides </li></ul><ul><li>Cough reflex </li></ul><ul><li>Phagocytic cells </li></ul>
  6. 6. Common Diseases contracted via the Respiratory Tract <ul><li>Common cold </li></ul><ul><li>Flu </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Whooping cough </li></ul><ul><li>Pneumonia </li></ul><ul><li>Measles </li></ul><ul><li>Strep Throat </li></ul><ul><li>Diphtheria </li></ul>
  7. 7. Mucus Membranes <ul><li>B. Gastrointestinal Tract </li></ul><ul><ul><li>Microbes gain entrance thru contaminated food & water or fingers & hands. </li></ul></ul><ul><ul><li>Most microbes that enter the G.I. Tract are destroyed by HCL & enzymes of stomach or bile & enzymes of small intestine. </li></ul></ul>
  8. 8. Common diseases contracted via the G.I. Tract <ul><li>Salmonellosis </li></ul><ul><ul><li>Salmonella sp. </li></ul></ul><ul><li>Shigellosis </li></ul><ul><ul><li>Shigella sp. </li></ul></ul><ul><li>Cholera </li></ul><ul><ul><li>Vibrio cholorea </li></ul></ul><ul><li>Ulcers </li></ul><ul><ul><li>Helicobacter pylori </li></ul></ul><ul><li>Botulism </li></ul><ul><ul><li>Clostridium botulinum </li></ul></ul>
  9. 9. Fecal - Oral Diseases <ul><li>These pathogens enter the G.I. Tract at one end and exit at the other end. </li></ul><ul><li>Spread by contaminated hands & fingers or contaminated food & water </li></ul><ul><li>Poor personal hygiene. </li></ul>
  10. 10. Mucus Membranes of the Genitourinary System Acidic urine Vaginal secretion- Acidic due to fermentation of glycogen by lactobacillus Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Chlamydia Chlamydia trachomatis HIV Herpes Simplex II
  11. 11. Mucus Membranes <ul><li>D. Conjunctiva – </li></ul><ul><li>Lacrymal secretion </li></ul><ul><li>Lysozyme </li></ul><ul><li>Trachoma </li></ul><ul><ul><li>Chlamydia trachomatis </li></ul></ul>
  12. 12. 2. Skin <ul><li>Skin - the largest organ of the body. </li></ul><ul><li>Sebaceous secretion-containing fatty acids </li></ul><ul><li>Resident flora </li></ul><ul><li>When unbroken is an effective barrier for most microorganisms. </li></ul><ul><li>Some microbes can gain entrance thru openings in the skin: hair follicles and sweat glands </li></ul>
  13. 13. 3. Parentarel <ul><li>Microorganisms are deposited into the tissues below the skin or mucus membranes </li></ul><ul><li>Punctures </li></ul><ul><li>injections </li></ul><ul><li>bites </li></ul><ul><li>scratches </li></ul><ul><li>surgery </li></ul><ul><li>splitting of skin due to swelling or dryness </li></ul>
  14. 14. Number of Invading Microbes <ul><li>LD 50 - Lethal Dose of a microbes toxin that will kill 50% of experimentally inoculated test animal </li></ul><ul><li>ID 50 - infectious dose required to cause disease in 50% of inoculated test animals </li></ul><ul><ul><li>Example: ID 50 for Vibrio cholerea 10 8 cells (100,000,000 cells) </li></ul></ul><ul><ul><li>ID 50 for Inhalation Anthrax - 5,000 to 10,000 spores </li></ul></ul>
  15. 15. How do Bacterial Pathogens penetrate Host Defenses? 1. Adherence - almost all pathogens have a means to attach to host tissue Binding Sites adhesins ligands
  16. 16. How Bacterial Pathogens Penetrate Host Defenses <ul><li>1. Adherence </li></ul><ul><li>2. Capsule </li></ul><ul><li>3. Enzymes </li></ul><ul><ul><li>A. leukocidins </li></ul></ul><ul><ul><li>B. Hemolysins </li></ul></ul><ul><ul><li>C. Coagulase </li></ul></ul><ul><ul><li>D. Kinases </li></ul></ul><ul><ul><li>E. Hyaluronidase </li></ul></ul><ul><ul><li>F. Collagenase </li></ul></ul><ul><ul><li>G. Necrotizing Factor </li></ul></ul>
  17. 17. Adhesins and ligands are usually on Fimbriae <ul><li>Neisseria gonorrhoeae </li></ul><ul><li>ETEC (Entertoxigenic E. coli) </li></ul><ul><li>Bordetella pertussis </li></ul>
  18. 18. 2. Capsules <ul><li>Prevent phagocytosis </li></ul><ul><li>Attachment </li></ul><ul><li>Streptococcus pneumoniae </li></ul><ul><li>Klebsiella pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Bacillus anthracis </li></ul><ul><li>Streptococcus mutans </li></ul><ul><li>Yersinia pestis </li></ul>K. pneumoniae
  19. 19. 3. Enzymes <ul><li>Many pathogens secrete enzymes that contribute to their pathogenicity </li></ul>
  20. 20. A. Leukocidins <ul><li>Attack certain types of WBC’s </li></ul><ul><li>1. Kills WBC’s which prevents phagocytosis </li></ul><ul><li>2. Releases & ruptures lysosomes </li></ul><ul><ul><li>lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage </li></ul></ul>
  21. 21. B. Hemolysins - cause the lysis of RBC’s Streptococci
  22. 22. 1. Alpha Hemolytic Streptococci - secrete hemolysins that cause the incomplete lysis or RBC’s
  23. 23. 2. Beta Hemolytic Streptococci - Secrete hemolysins that cause the complete lysis of RBC’s
  24. 24. C. Coagulase - cause blood to coagulate <ul><li>Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses </li></ul><ul><li>Staphylococci - are often coagulase positive </li></ul><ul><ul><li>boils </li></ul></ul><ul><ul><li>abscesses </li></ul></ul>
  25. 25. D. Kinases - enzymes that dissolve blood clots <ul><li>1. Streptokinase - Streptococci </li></ul><ul><li>2. Staphylokinase - Staphylococci </li></ul><ul><li>Helps to spread bacteria - Bacteremia </li></ul><ul><li>Streptokinase - used to dissolve blood clots in the Heart (Heart Attacks due to obstructed coronary blood vessels) </li></ul>
  26. 26. E. Hyaluronidase <ul><li>Breaks down Hyaluronic acid (found in connective tissues) </li></ul><ul><li>“Spreading Factor” </li></ul><ul><li>Mixed with a drug to help spread the drug through a body tissue </li></ul>
  27. 27. F. Collagenase <ul><li>Breaks down collagen (found in many connective tissues) </li></ul><ul><li>Clostridium perfringens - Gas Gangrene </li></ul><ul><ul><li>uses this to spread thru muscle tissue </li></ul></ul>
  28. 28. G. Necrotizing Factor - Causes death (necrosis) to tissue cells “ Flesh Eating Bacteria”
  29. 29. Bacterial Toxins <ul><li>Poisonous substances produced by microorganisms </li></ul><ul><li>Toxins - primary factor - pathogenicity </li></ul><ul><li>220 known bacterial toxins </li></ul><ul><ul><li>40% cause disease by damaging the Eukaryotic cell membrane </li></ul></ul><ul><li>Toxemia </li></ul><ul><ul><li>Toxins in the bloodstream </li></ul></ul>
  30. 30. Types of Toxins <ul><li>1. Exotoxins </li></ul><ul><ul><li>Exotoxins are generated by the bacteria and actively secreted </li></ul></ul><ul><ul><li>Secreted outside the bacterial cell </li></ul></ul><ul><li>2. Endotoxins </li></ul><ul><ul><li>Part of the outer cell wall of Gram (-) bacteria </li></ul></ul><ul><ul><li>The body's response to endotoxin can involve severe inflammation. </li></ul></ul>
  31. 31. Exotoxins <ul><li>Mostly seen in Gram (+) Bacteria </li></ul><ul><li>Heat labile, can be inactivated by heating at 60-80 ۠ C. </li></ul><ul><li>Excreted [ secreted] from the microbial cells into the surrounding ie culture media or circulatory system </li></ul><ul><li>Don’t require bacterial death or cell lysis for their release. </li></ul>
  32. 32. Types of Exotoxins <ul><li>1. Cytotoxins </li></ul><ul><ul><li>Kill cells- shigella, vibrio </li></ul></ul><ul><li>2. Neurotoxins </li></ul><ul><ul><li>Interfere with normal nerve impulses </li></ul></ul><ul><ul><li>Clostridium botulinum </li></ul></ul><ul><ul><li>Clostridium tetani </li></ul></ul><ul><li>3. Enterotoxins </li></ul><ul><ul><li>Effect cells lining the G.I. Tract </li></ul></ul><ul><ul><li>E. coli </li></ul></ul><ul><ul><li>Salmonella </li></ul></ul>
  33. 33. Response to Toxins <ul><li>If exposed to exotoxins: antibodies against the toxin ( antitoxins ) </li></ul><ul><li>Exotoxins inactivated ( heat, formalin or phenol) no longer cause disease, but stimulate the production of antitoxin </li></ul><ul><ul><li>altered exotoxins - Toxoids </li></ul></ul><ul><li>Toxoids - injected to stimulate the production of antitoxins and provide immunity </li></ul>
  34. 34. Endotoxins <ul><li>Part of the Gram (-) Bacterial cell wall. </li></ul><ul><li>Biological activity or toxicity of endotoxin is largely due to lipid A. </li></ul><ul><li>Relatively heat stable can withstand heat over 60 ۠ C for many hours. </li></ul><ul><li>Released upon cell lysis or death. </li></ul><ul><li>Less potent than exotoxins, active in large doses only. </li></ul><ul><li>Pyrogenic often produce fever in hosts. </li></ul><ul><li>Salmonella, Shigella, Escherichia, Neisseria. </li></ul>
  35. 35. Bacteriocin <ul><li>Bacteriocins were first discovered by A. Gratia in 1925. </li></ul><ul><li>He called his first discovery a colicine because it killed E. coli. </li></ul><ul><li>Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). </li></ul><ul><li>They are typically considered to be narrow spectrum antibiotics, though this has been debated. </li></ul>
  36. 36. <ul><li>Classification: </li></ul><ul><li>Class I: Small peptide inhibitors . </li></ul><ul><li>Class II: Small heat-stable proteins . </li></ul><ul><li>Class III: Large, heat-labile protein bacteriocins </li></ul>
  37. 37. <ul><li>Medical significance </li></ul><ul><li>Bacteriocins are of interest in medicine because they are made by non-pathogenic bacteria that normally colonize the human body. </li></ul><ul><li>Loss of these harmless bacteria following antibiotic use may allow opportunistic pathogenic bacteria to invade the human body. </li></ul>

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