Microbial Pathogenicity (classification and steps).pptx

To cause disease a pathogen must:
1. Gain access to the host
2. Adhere to host tissues
3. Penetrate or evade host defences
4. Damage the host, either:
- Directly
- Accumulation of microbial wastes

1. Microbial Pathogenicity Dr Lopamudra Samantaray Asst. professor, Utkal university

2. Animal & Microorganisms relationship Saprophytes Free living microbes Dead & Decaying matter Except: B. subtilis (opportunistic infection) Parasites Microbes establish & multiply in host Pathogen: Produce disease Commensals: Live in harmony with host without causing disease Facultative pathogen: host resistance ↓ ↓

3. DEFINITIONS Disease and Infectious Disease Disease Any deviation from a condition of good health and well-being Infectious Disease A disease condition caused by the presence or growth of infectious microorganisms or parasites

4. Entry of pathogen: Infection: Pathogen enter----establish ---invade Normal anatomical barrier---multiply—infection Lodgement & multiplication of pathogen in or on tissue of host Infection-  disease Colonization Pathogen enter—multiply—not invade/elicit immune response

5. Classification of Infections Acute infection vs. chronic infection Acute Infection An infection characterized by sudden onset, rapid progression, and often with severe symptoms Chronic Infection An infection characterized by delayed onset and slow progression

6. Primary infection vs. secondary infection Primary Infection An infection that develops in an otherwise healthy individual Secondary Infection An infection that develops in an individual who is already infected with a different pathogen

7. Localized infection vs. systemic infection Localized Infection An infection that is restricted to a specific location or region within the body of the host Systemic Infection An infection that has spread to several regions or areas in the body of the host

8. Clinical, subclinical, atypical, Latent infection Clinical Infection An infection with obvious observable or detectable symptoms Subclinical/ Asymptomatic Infection An infection with few or no obvious symptoms with active infection Atypical Infection No characteristic Latent infection Infection—inactive or dormant latent/hidden form—↓↓ host resistance---proliferation of pathogen---  Disease

9. Opportunistic infection An infection caused by microorganisms that are commonly found in the host’s environment. This term is often used to refer to infections caused by organisms in the normal flora

10. DEFINITIONS The suffix “- emia ” A suffix meaning “presence of an infectious agent” Bacteremia = Presence of infectious bacteria Viremia = Presence of infectious virus Fungemia = Presence of infectious fungus Septicemia = Presence of an infectious agent in the bloodstream

11. Source ….Reservoir Source: Person/Animal/Object from which a microorganism is transmitted to host Reservoir: Natural habitat in which organism multiply, live. Maintain parasite in nature Asymptomatic infection

12. Source ….Reservoir Infection Source of infection Reservoir Tetanus Clostridium tetani Soil Soil Hookworm Soil contaminated with larva Man

13. CARRIERS Carriers Person/ infectious agent in absence of clinical symptom & Shed from body via contact, air or secretions Inadequate Treatment/Immune response ---incomplete elimination of organism Less infectious than Cases BUT More Dangerous Types: Incubatory carrier : These people can spread a pathogen before they show symptoms of the illness .  Eg. Measels , Mumps, Polio, Hepatitis B, Influenza, Diphtheria etc Healthy carrier : Subclinical infection without suffering from disease converted into carrier eg. Diphtheria etc. Convalescent carrier : Recovered from disease but still continue to harbour pathogen-  shed from body

14. CARRIERS Based on duration: Temporary carrier : <6months duration Healthy, incubatory, convalescent carrier Chronic carrier : Indefinite period Hepatitis B, Typhoid Based on Source: Contact carrier : acquire pathogen from patient Paradoxical carrier : Acquire infection from another carrier

15. MODE OF TRANSMISSION Contact Direct: STD Indirect: by objects Inhalational process of breathing in Ingestion Inoculation/ Percutaneous Animal bite Direct inoculation into tissue following injury blood borne infections

16. MODE OF TRANSMISSION Vector borne Mechanical vector, Biological vector Mosquito Sandfly Ticks Housefly Tsetse fly

17. MODE OF TRANSMISSION Vertical Transplacental: TORCH ( toxoplasmosis, others(Syphilis, Hepatitis B), rubella, Cytomegalovirus (CMV by HHV-5), and herpes simplex virus ) During passage through birth canal: Gp B streptococcus, HIV Laboratory induced

18. MICROBIAL PATHOGENICITY Pathogenicity = ability to cause disease Virulence = degree of pathogenicity Pathogens must first gain access to the host Must adhere and penetrate before infection i s established Then must continually evade host defenses Infection usually causes host damage: disease

19. Virulence variations Spontaneous Induced ↓----Attenuation Passage in unfavourable conditions Repeated subculture artificial media Prolonged storage Growth in presence of inhibitors/high temperature ↑---Exaltation Serial passage in susceptible host

20. MICROBIAL PATHOGENICITY To cause disease a pathogen must: 1. Gain access to the host 2. Adhere to host tissues 3. Penetrate or evade host defences 4. Damage the host, either: - Directly - Accumulation of microbial wastes

21. Microbial mechanism of pathogenicity

22. Entry Into Host 1. Portals of Entry A. Mucus membranes (moist mucosa) -most common route for most pathogens -entry through mucus membranes: 1. respiratory tract (most common) 2. gastrointestinal tract 3. urinary/genital tracts 4. conjunctiva

23. Entry Into Host B. Skin (keratinized cutaneous membrane) -some pathogens infect hair follicles and sweat glands -few can colonize surface -unless broken, skin is usually an impermeable barrier to microbes

24. Entry Into Host C. Pene t ral route penetrate skin: punctures, injections, bites, cuts, surgery, etc. deposit organisms directly into deeper t issues most microbes must enter through their preferred portal of entry in order to cause disease some can cause disease from many routes of entry most usually also exit the host from the same original portal to spread disease

25. 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

26. Entry Into Host 3. Adherence = attachment to the host by the m icrobe at portal of entry usually necessary for virulence blocking adhesion can prevent disease pathogen has surface molecules called a dhesins 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

27. Entry Into Host 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; a large mass is formed the biofilm is resistant to Disinfectants and antibiotics (outer layer protects inner layers) problem for catheters and surgical implants: serves as chronic reservoir

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

29. Penetration of Host Defences 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 B. Fimbriae + Opa (membrane protein) used by Neisseria gohorrhoeae : -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

30. Penetration of Host Defences 3. Enzymes (exoenzymes) A. Coagulases: clot fibrin in blood to create protective barrier against host defenses B. Kinases: dissolve clots (fibrinolysis) to allow escape from isolated wounds e.g. Streptokinase ( Streptococcus pyogenes ), Staphylokinase ( Staphylococcus aureus ) C. Hyaluronidase: hydrolyses 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)

31. Penetration of Host Defences D. Collagenase: breaks down collagen (fibrous part of connective tissue) for invasion into muscles and organs e.g. Clostridium species E. 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

32. Penetration of Host Defences 4. Antigenic Variation -pathogen alters its surface antigens to escape attack by antibodies and immune cells e.g. Neisseria gonorrhoeae -can alter which one is being expressed e.g. influenza virus -constant genetic recombination between flu viruses: always new spike proteins hemagglutinin (H) protein and neuraminidase (N) protein H1N1- swine flu H5N1- bird flu

33. Penetration of Host Defences 5. Penetration into Host Cytoskeleton -use actin of host cell to penetrate and move within the cell A. Invasins : surface proteins produced by bacteria to control actin e.g. Salmonella -rearrange actin: cause the cell membrane to wrap around the microbe and take it into the cell (endocytosis) -allows Salmonella to penetrate intestinal epithelium e.g. Shigella and Listeria -trigger endocytosis -polymerize actin behind bacterium to propel through host cell B. Cadherin: allows penetration between cells at intercellular junctions e.g. Shigella and Listeria : move between cells at cell junctions.

34. Damage to Host Cells 1. Using Hosts Nutrients e.g. iron -required for all cells 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: secreted by bacteria to compete iron from host proteins, siderophore iron complex then absorbed by bacteria

35. 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

36. Damage to Host Cells 3. Production of Toxins Toxins = poisonous substance produced by microbes -tend to cause widespread damage/disease in host -may be necessary for virulence A. Exotoxins -produced inside the bacteria and either secreted or released following microbe lysis -toxin genes are often found on plasmids or via lysogenic phages -most are enzymes -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

37. Damage to Host Cells -three 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 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 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

38. 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, tissue necrosis, shock and death e.g. endotoxic shock: critical loss of blood pressure due to bacterial endotoxins (LPS) 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 -Limulus Amoebocyte Lysate Assay: on horseshoe crab blood which contains amoebocytes that will lyse and clot in the presence of extremely low levels of LPS

39. Plasmids, Lysogeny and Pathogenicity -plasmids carry genes for resistance to antibiotics and/or virulence factors (e.g. exotoxins, fimbriae) between bacteria allowing new bacteria to become pathogenic e.g. hemorrhagic E. coli ( fimbrae + shiga toxin) -prophages can result in lysogenic conversion that results in pathogenic ability of the bacteria carrying them (new production of endotoxin) e.g. Diptheria toxin ( Cornebacterium ) Cholera toxin ( Vibrio ) -phage can be transmitted to nonpathogenic strains making them virulent

40. Pathogenic Properties of Virus 1. Mechani sms to evade host defenses A. Grow inside host cells to hide from immune defence B. Kill immune cells e.g. HIV – TH 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

41. Pathogenic Properties of Virus D. syncytium formation (neighboring cells fuse together) e.g. Varicella E. change in cell function e.g. Measles F. production of interferons by host cell (triggers host immune response) G. induce antigenic changes on host cell surface (triggers destruction of infected cell by host immune response) H. induce chromosomal changes I. cell transformation: may activate or deliver oncogenes resulting in loss of contact inhibition (cancer) e.g. Papilloma virus

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

43. 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 e.g. shellfish poisoning (dinoflagellates)