University:
Kentucky State University
Course:
BIO 317 | Medical Microbiology
Academic year:

2019
Views:

290

Pages:

32
Author:

palangresq3v

To be or not to be a pathogen Microbial Mechanisms of Pathogeneicity Determinants of Pathogenicity: – 1) Ability to survive host’s natural defense mechanisms – 2) Ability to multiply to large numbers – 3) Adherence: ability for microorganism to be able to attach firmly to host’s epithelial surface so that they are not easily dislodged (Removed). Steps in the pathogenesis of Infectious diseases • Entry • Attachment • Multiplication • Invasion • Evasion of Host defenses • Da 2 3/26/2022 Portals of Entry • Mucosal membranes of Gastrointestinal tract, urogenital tract, upper respiratory tract. • Skin: intact skin is a barrier except for damaged skin through wounds, surgery, or burns • Parenteral route: contaminated syringe, animal bites, surgery or blood transfusions. Preferred route of entry. Number of invading Microbes. ID50: B.anthrax skin 10-50 endospores Inhalation 10.000-20,000 Gastrointestinal 250,000 LD50 toxin botulinum toxin vs. shiga toxin 0.03ng/Kg vs 250ng/Kg 3/26/2022 3 Attachment • Bacteria attach to cells by chemical substances on their cell surface called ADHESINS. Through attachment to host RECEPTORS • Adhesins may be on – (i) Pilli – (ii) Capsules • Adherence facilitates multiplication, colonization & subsequent penetration of epithelia. • E.g enteropathogenic E.coli • Adhesins on fimbrea that allow adherence to special cells in the small intestine. • E.g. T. pallidum, N. gonorrhoeae 3/26/2022 4 Evasion of Host defenses Intracellular pathogens: hiding from immune system : Some Non capsulated organisms are easily phagocytosed but relatively resistant to digestion within phagocyte and survive and multiply within phagocyte until phagocyte is killed and are called INTRACELLULAR organisms e.g.M.tb. -Escaping phagocytoses: -Antigenic variation: 3/26/2022 5 Escaping phagocytoses Avoiding Contact with Phagocytes – Hides the antigenic surface. – remain confined in regions inaccessible to phagocytes. – inhibit phagocyte chemotaxisE.g SpyCEP in Streptococcus pyogens. What is this??? Inhibition of Phagocytic Engulfment – Capsules – Mycobacterial cell wall that resist phagocytosis (mycolic acid). – M protein in Streptococcus helps bacteria resist phagocytoses. Survival Inside of Cells – Inhibition of fusion of the phagocytic lysosomes (granules) with the phagosomeToxoplasma gondii prevent formation of phagolysosome. – Survival inside the phagolysosome – Bacteria that can survive within macrophages. – Escape from the phagosome(Rickettsia enter host cells in membranebound vacuoles (phagosomes) but are free in the cytoplasm a short time later, perhaps in as little as 30 seconds. A bacterial enzyme, phospholipase A, may be responsible for dissolution of the phagosome membrane. 3/26/2022 . . Phagocytes . . – Products of Bacteria that Kill or Damage 6 Antigenic variation changing surface antigens, activating alternative genes 3/26/2022 Dr. S.M.A.Abdelmalek 7 Invasion of host tissues • Enzymes • Penetration of host cell cytoskeleton 3/26/2022 8 Enzymes • Coagulases: fibrinogen into fibrin wall out bacteria • Kinases: breakdown fibrin to allow spread of microbe. • Hayaluronidases: break hyaluronic acid that hold cells of the connective tissue together allowing spread of microbe. • Collagenases: breaks down collagen that holds connective tissue of muscles and other body organs together. • IgA proteases: breaks down the IgA that forms to prevent adherence (CNS) 3/26/2022 9 Penetration into host cell cytoskeleton: • • 3/26/2022 invasins of Salmonella The use of actin of the cell to allow the movement of the bacteria within the cell and to other adjacent cells.e.g. Shigella, Listeria. 10 Damage • 1- Using Host Nutrients: Siderophores Host cell iron transport proteins: lactofe transferring, and ferreting, hemoglobin When iron is in short supply, bacteria develop siderophore receptors, specialized proteins that steal iron from the host 3/26/2022 11 Damage Direct Damage §Use of nutrients of the cell damages the cell: protozoa, viruses, and intracellular bacteria. §Damage of phagocytic cells §Use of enzymes for penetration §Toxin production §Toxin vs. Toxoid §Toxigenicity §Toxemia. §Exotoxins and Endotoxins 3/26/2022 12 BACTERIAL TOXINS 3/26/2022 13 Exotoxins Naming according to: • Attacked cell: neurotoxin, cardiotoxin,hepatotoxin enterotoxin… • Structure and function – A-B toxin – Membrane disrupting toxin – Superantigens – Genotoxins: Toxins that damage the DNA such toxin – Can cause cancer e.g Helicobacter sp. And heamophilus ducray 3/26/2022 14 Exotoxins Naming according to: • Attacked cell: neurotoxin, cardiotoxin,hepatotoxin enterotoxin… • Structure and function – A-B toxin – Membrane disrupting toxin – Superantigens – Genotoxins 3/26/2022 15 A-B TOXINS A-B Toxins • Part A: active enzyme component • Part B: Binding component Steps • Toxin released • B binds to host receptor and transported to cytoplasm • A inhibits protein synthesis of host and host cell dies and B is released from cell Example • Diptheria toxin • Corynebacterium diphtheriae 3/26/2022 16 Membrane disrupting toxins Disrupt host plasma membrane • Protein channels • Phospholipid disruption Varieties • Leukocidins – Target phagocytes – Protein channels – Ex. Staphylococci leukocidins • Hemolysins – Target RBCs – Protein channels – Ex. Streptococci (streptolysin) SUPERANTIGENS • • • • Invoke very strong immune response T cells Release lots of cytokines which can cause severe symptoms Ex. Staphylococci and food poisoning toxins 3/26/2022 17 Genotoxins • Damages the genetic information within a cell. • All mutagens are genotoxic, whereas not all genotoxic substances are mutagenic. • The alteration can have direct or indirect effects on the DNA: • Such as induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. • The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. • Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis. • E.g: Helicobacter species Haemophilus ducreyi 3/26/2022 18 Exotoxins vs. Endotoxins 3/26/2022 19 3/26/2022 20 Endotoxins 3/26/2022 Dr. S.M.A.Abdelmalek 21 LAL 3/26/2022 Dr. S.M.A.Abdelmalek 22 Plasmids Lysogeny and Pathogenicity Toxins and virulence factors produced due to genes carried on Plasmids Tetanus, heat labile staphylococcus enterotoxin, dextransucrase of Streptococcus mutants, fimbrea of enteropathogenic E.coli Toxins produced due to genes of prophages: • Diphtheria toxin, Erythrogenic toxin (STREPTOCOCUS), Staphylococcal enterotoxin, Botulinum neurotoxin, Capsule of Streptococcus pneumoniae (not exactly a toxin but contributes to virulence, Vibrio toxin 3/26/2022 23 3/26/2022 24 Pathogenic properties of viruses • Viral mechanisms for evading host defenses attachment sites for receptors on host cells: • E.g. attachment sites may mimic substance useful to the cell e.g. rabies particle and acetylcholine. • E.g the attachment site for Aids virus is hidden on the virus surface so antibodies cannot neutralize it • Cytopathic effects of viruses • infection of a host cell by an animal virus usually results in death of the cell due to: • Accumulation of large numbers of viruses, effects of the virus that change the permeability of the host cell plasma membrane, or by inhibition of synthesis of the host cell’s DNA, RNA, and proteins. • Visible effects that can lead to death or damage of a host cell are called cytopathic effects (CPEs 3/26/2022 25 Types of CPE Cytocidal viruses 1. stop mitosis (herpessimplex virus) 1. Release of lysozomal enzymes leading to death of the cell. 2. Inclusion bodies: their presence help in diagnosis of the infecting viruse.g. Negri bodies of rabies and owl eyes of CMV 3. Synciytium formation: measles virus 4. Changes in host cell functions e.g. measles reduce IL-12 production 5. Interferon's production 6. Cell destruction due to antigenic changes on cell surface. 7. Transformation and loss of Contact inhibition 8. Chromosomal changes (oncogenes) 3/26/2022 26 3/26/2022 27 Pathogenic properties of Fungi • Fungi---some fungi can cause disease, but as a group they do not have a well-defined set of virulence factors. • a. Some fungi do produce toxic chemicals. Some fungal toxins must be ingested to cause disease, others can be inhaled. – E.g. One example of a fungus disease caused by a toxin is ergotism. This was common in Europe in the Middle Ages and is believed by some to have been the cause of the phenomena blamed on witchcraft early in the history of this country. – Peanuts, peanut butter, etc. may contain traces of aflatoxin, a toxin formed by the mold Aspergillus flavus. This toxin can possible act as a carcinogen. – Some mushrooms produce a strong toxin that destroys the liver. These are called mycotoxins and include phalloidin and amantin. One mushroom, Amanita phalloides, is called the death angel. b. Two fungi that cause skin infections, Candida albicans and Trichophyton secrete proteases, which may modify host cell membranes to allow attachment of the fungi. c. The body may produce an allergic response to the fungus. d. At least one fungus organism, Cryptococcus neoformans, produces a capsule that helps it resist phagocytosis. 3/26/2022 28 Pathogenic properties of protozoa and Protozoa this group causes disease by various means: • a. Plasmodium (causative agent of malaria) invades host cells (RBC) and causes them to rupture. Waste products are also toxic to the host. • b. Toxoplasma—attaches to macrophages and enters by phagocytosis. The parasite prevents normal digestion by lysosome enzymes and multiplies within the phagocytic vesicle. • c. Giardia lamblia---attaches to host cells and digests the host cells and tissue fluids. • D. Some protozoa are able to alter their antigenic properties, making it difficult for the immune system of the host to produce effective antibodies. Giardia and Trypanosoma have this characteristic and can cause long-lasting infections. 3/26/2022 29 Pathogenic properties of helminthes • • • • Mechanical damage Large masses of parasites may interfere with normal function. compete with the host for nutrients. Waste products of the parasite may also be harmful. • Algae---only a few species of algae are harmful to humans. For example, some dinoflagellates produce a neurotoxin, saxitoxin, which is ingested by mollusks. Although the mollusk is not harmed, humans eating the toxin develop symptoms similar to botulism (paralytic shellfish poisoning). 3/26/2022 30 3/26/2022 31 • • • • • • Portals of Exit Related to the infected part of the body. Respiratory tract Gastrointestinal tract Genitourinary tract Skin Biting insects 3/26/2022 32

Microbial Mechanisms of Pathogeneicity

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