Microbial pathogens can cause disease through several mechanisms: 1. They produce toxins or enzymes like exotoxins and endotoxins that damage host cells. Common exotoxins include neurotoxins and enterotoxins. 2. They secrete adhesins and other factors like capsules that help them attach to and evade host defenses, making it easier to infect tissues. 3. After entering through mucous membranes or breaks in the skin, pathogens must overcome the host's immune responses and outgrow the local microbiota to cause illness. Virulence factors play an important role in this process.

1. Microbial Mechanisms of Pathogenesis

2. Pathogenesis The word comes from the Greek pathos , "disease", and genesis , creation. The term pathogenesis means step by step development of a disease. 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. Caused by a microbial, chemical or physical agent.

3. Pathogenicity - Ability to cause disease Virulence - Degree of pathogenicity Many properties that determine a microbe’s pathogenicity or virulence are unclear or unknown But, when a microbe overpowers the hosts defenses, disease results!

4. Portals of Entry 1. Mucus Membranes 2. Skin 3. Parenteral

5. 1. Mucus Membranes A. Respiratory Tract Sticky mucous secretion Muco polysachharides Cough reflex Phagocytic cells

6. Common Diseases contracted via the Respiratory Tract Common cold Flu Tuberculosis Whooping cough Pneumonia Measles Strep Throat Diphtheria

7. Mucus Membranes B. Gastrointestinal Tract Microbes gain entrance thru contaminated food & water or fingers & hands. Most microbes that enter the G.I. Tract are destroyed by HCL & enzymes of stomach or bile & enzymes of small intestine.

8. Common diseases contracted via the G.I. Tract Salmonellosis Salmonella sp. Shigellosis Shigella sp. Cholera Vibrio cholorea Ulcers Helicobacter pylori Botulism Clostridium botulinum

9. Fecal - Oral Diseases These pathogens enter the G.I. Tract at one end and exit at the other end. Spread by contaminated hands & fingers or contaminated food & water Poor personal hygiene.

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. Mucus Membranes D. Conjunctiva – Lacrymal secretion Lysozyme Trachoma Chlamydia trachomatis

12. 2. Skin Skin - the largest organ of the body. Sebaceous secretion-containing fatty acids Resident flora When unbroken is an effective barrier for most microorganisms. Some microbes can gain entrance thru openings in the skin: hair follicles and sweat glands

13. 3. Parentarel Microorganisms are deposited into the tissues below the skin or mucus membranes Punctures injections bites scratches surgery splitting of skin due to swelling or dryness

14. Number of Invading Microbes LD 50 - Lethal Dose of a microbes toxin that will kill 50% of experimentally inoculated test animal ID 50 - infectious dose required to cause disease in 50% of inoculated test animals Example: ID 50 for Vibrio cholerea 10 8 cells (100,000,000 cells) ID 50 for Inhalation Anthrax - 5,000 to 10,000 spores

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. How Bacterial Pathogens Penetrate Host Defenses 1. Adherence 2. Capsule 3. Enzymes A. leukocidins B. Hemolysins C. Coagulase D. Kinases E. Hyaluronidase F. Collagenase G. Necrotizing Factor

17. Adhesins and ligands are usually on Fimbriae Neisseria gonorrhoeae ETEC (Entertoxigenic E. coli) Bordetella pertussis

18. 2. Capsules Prevent phagocytosis Attachment Streptococcus pneumoniae Klebsiella pneumoniae Haemophilus influenzae Bacillus anthracis Streptococcus mutans Yersinia pestis K. pneumoniae

19. 3. Enzymes Many pathogens secrete enzymes that contribute to their pathogenicity

20. A. Leukocidins Attack certain types of WBC’s 1. Kills WBC’s which prevents phagocytosis 2. Releases & ruptures lysosomes lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage

21. B. Hemolysins - cause the lysis of RBC’s Streptococci

22. 1. Alpha Hemolytic Streptococci - secrete hemolysins that cause the incomplete lysis or RBC’s

23. 2. Beta Hemolytic Streptococci - Secrete hemolysins that cause the complete lysis of RBC’s

24. C. Coagulase - cause blood to coagulate Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses Staphylococci - are often coagulase positive boils abscesses

25. D. Kinases - enzymes that dissolve blood clots 1. Streptokinase - Streptococci 2. Staphylokinase - Staphylococci Helps to spread bacteria - Bacteremia Streptokinase - used to dissolve blood clots in the Heart (Heart Attacks due to obstructed coronary blood vessels)

26. E. Hyaluronidase Breaks down Hyaluronic acid (found in connective tissues) “Spreading Factor” Mixed with a drug to help spread the drug through a body tissue

27. F. Collagenase Breaks down collagen (found in many connective tissues) Clostridium perfringens - Gas Gangrene uses this to spread thru muscle tissue

28. G. Necrotizing Factor - Causes death (necrosis) to tissue cells “ Flesh Eating Bacteria”

29. Bacterial Toxins Poisonous substances produced by microorganisms Toxins - primary factor - pathogenicity 220 known bacterial toxins 40% cause disease by damaging the Eukaryotic cell membrane Toxemia Toxins in the bloodstream

30. Types of Toxins 1. Exotoxins Exotoxins are generated by the bacteria and actively secreted Secreted outside the bacterial cell 2. Endotoxins Part of the outer cell wall of Gram (-) bacteria The body's response to endotoxin can involve severe inflammation.

31. Exotoxins Mostly seen in Gram (+) Bacteria Heat labile, can be inactivated by heating at 60-80 ۠ C. Excreted [ secreted] from the microbial cells into the surrounding ie culture media or circulatory system Don’t require bacterial death or cell lysis for their release.

32. Types of Exotoxins 1. Cytotoxins Kill cells- shigella, vibrio 2. Neurotoxins Interfere with normal nerve impulses Clostridium botulinum Clostridium tetani 3. Enterotoxins Effect cells lining the G.I. Tract E. coli Salmonella

33. Response to Toxins If exposed to exotoxins: antibodies against the toxin ( antitoxins ) Exotoxins inactivated ( heat, formalin or phenol) no longer cause disease, but stimulate the production of antitoxin altered exotoxins - Toxoids Toxoids - injected to stimulate the production of antitoxins and provide immunity

34. Endotoxins Part of the Gram (-) Bacterial cell wall. Biological activity or toxicity of endotoxin is largely due to lipid A. Relatively heat stable can withstand heat over 60 ۠ C for many hours. Released upon cell lysis or death. Less potent than exotoxins, active in large doses only. Pyrogenic often produce fever in hosts. Salmonella, Shigella, Escherichia, Neisseria.

35. Bacteriocin Bacteriocins were first discovered by A. Gratia in 1925. He called his first discovery a colicine because it killed E. coli. Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are typically considered to be narrow spectrum antibiotics, though this has been debated.

36. Classification: Class I: Small peptide inhibitors . Class II: Small heat-stable proteins . Class III: Large, heat-labile protein bacteriocins

37. Medical significance Bacteriocins are of interest in medicine because they are made by non-pathogenic bacteria that normally colonize the human body. Loss of these harmless bacteria following antibiotic use may allow opportunistic pathogenic bacteria to invade the human body.