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    Bacterial Pathogenesis

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    The document discusses bacterial pathogenesis, including the types of bacterial pathogens, virulence factors that facilitate disease, and the general steps in the pathogenesis process from transmission to infection to host response. It provides details on various mechanisms bacteria use for adhesion, colonization, immune evasion, and disease production through toxins and enzymes. The summary also lists some important exotoxins and the mechanisms through which they cause disease.

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    Bacterial Pathogenesis

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    The document discusses bacterial pathogenesis, including the types of bacterial pathogens, virulence factors that facilitate disease, and the general steps in the pathogenesis process from transmission to infection to host response. It provides details on various mechanisms bacteria use for adhesion, colonization, immune evasion, and disease production through toxins and enzymes. The summary also lists some important exotoxins and the mechanisms through which they cause disease.

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    The document discusses bacterial pathogenesis, including the types of bacterial pathogens, virulence factors that facilitate disease, and the general steps in the pathogenesis process from transmission to infection to host response. It provides details on various mechanisms bacteria use for adhesion, colonization, immune evasion, and disease production through toxins and enzymes. The summary also lists some important exotoxins and the mechanisms through which they cause disease.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    3K views36 pages

    Bacterial Pathogenesis

    Uploaded by

    api-19969058
    The document discusses bacterial pathogenesis, including the types of bacterial pathogens, virulence factors that facilitate disease, and the general steps in the pathogenesis process from transmission to infection to host response. It provides details on various mechanisms bacteria use for adhesion, colonization, immune evasion, and disease production through toxins and enzymes. The summary also lists some important exotoxins and the mechanisms through which they cause disease.

    Copyright:

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    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 36

    Dr.

    Mejbah Uddin Ahmed


    Bacterial Pathogenesis

    Bacterial pathogens are of two types:


    a) Primary pathogen: Are capable of
    establishing infection and causing disease in
    previously healthy individuals.
    b)Opportunistic pathogens: Are capable of
    establishing infection and causing disease in
    immunocompromised individuals.
    Bacterial Pathogenesis

    Virulence: Is a measure of a microbe’s ability


    to cause disease. Both primary and
    opportunistic pathogens possesses several
    virulence factors that facilitate pathogenesis.
    Pathogenesis
    Virulence Factors:
    ●Adhesins: Pili or fimbria, teichoic acid, M protein,
    haemaglutinin, Curli protein, slime layer, capsule.
    ● several enzymes: Coagulase, hyaluronidase,
    collagenase, IgA protease etc.
    ● Toxins.
    ● Antigenic variation.
    ● Anti phagocytic activity.
    ● Intracellular survival.
    Pathogenesis

    Steps of bacterial Pathogenesis: Generalized


    sequences of events of infection are as
    follows:
    A) Transmission ( when normal flora cause
    disease does not need transmission).
    B) Evasion of primary host defense e.g. skin,
    mucous membrane, stomach acid etc.
    C) Adherence at the site of infection.
    Pathogenesis

    Steps of bacterial Pathogenesis:


    D) Colonization and growth at that side.
    E) Disease production by toxin or invasion
    and inflammation.
    F) Host response/Immune response.
    G) Progression or resolution of disease.
    Steps of pathogenesis
    A) Transmission:
    1) Human to human transmission
    a) Direct contact.
    b) No direct contact.
    c) Vertical.
    d) Blood borne.
    a) Direct contact: Intimate close contact; e.g.
    sexual: Gonorrhea.
    b) No direct contact: Through airborne
    respiratory droplets, fecal contamination of
    food and water, fomites etc.
    Steps of pathogenesis

    c) Vertical transmission:
    From mother to fetus during intrauterine and
    perinatal life.
    •Transplacental: Treponema pallidum,
    Listeria monocytogens.
    •Within birth canal: Streptococcus agalactiae,
    Esch. Coli, Chlamydia, N. gonorrhoeae.
    •Breast milk: Staph. Aureus.
    Steps of pathogenesis

    d) Blood borne: During blood transfusion or


    intravenous drug use: Syphilis.
    2) Nonhuman to human:
    a) Soil: Spore of clostridium causes wound
    infection.
    b) Water: V. cholerae, Salmonella, L. pneumophia.
    c)Food: Salmonella, Clostridium botulinum.
    d) Animal source (zoonotic).
    Pathogenesis
    d) Animal source (zoonotic):

    Bacterium Reservoir Disease


    B. anthrcis Domestic Anthrax
    animals
    Yersinia Domestic animals, Diarrhea, sepsis
    Rodents

    Leptospira Rat and dog Leptospirosis


    Rickettsia Rat and dog Rocky mounted spotted
    fever
    Steps of pathogenesis

    Adhesion : Several structures are involved in


    adhesion by the interactions between specific
    receptors on the host tissue and ligands on
    the bacterial surface.
    Steps of pathogenesis
    Colonization: Successful colonization is also
    require to acquire essential nutrients for
    growth.
    B)Immune evasion: Once colonize,
    pathogenic bacteria are able to evade host
    immune response by avoiding or
    neutralizing these highly efficient clearance
    systems.
    Pathogenesis

    Following structures and mechanisms are


    involved in immune evasion:
    Antiphagocytic action:
    ●Capsule: Capsule inhibits phagocytosis by
    preventing interaction between antibody and C3
    bound to outer membrane of bacteria and their
    receptors.
    Pathogenesis

    ●Antigenic variation:
    Variation occurs in surface antigen during the
    course of infection and helps in avoidance of
    specific immune response directed at those
    antigens e.g. N. meningitidis.
    Pathogenesis

    ● IgA protease:
    Several bacteria produces protease enzyme
    that specifically cleaves secretory IgA and
    helps the bacteria to persist them on he
    mucosal surface and resist phagocytosis.
    Pathogenesis

    ● Serum resistance:
    To survive in the bloodstream some
    bacteria are able to resist complement
    mediated lysis. Which possess “O” side
    chain in their LPS are more resistant.
    Pathogenesis
    ●Intracellular survival after
    phagocytosis by following
    mechanisms:
    1)Inhibition of the fusion of phagosome
    with lysosome by “exported repetitive
    protein”: e.g. Mycobacterium.
    Pathogenesis

    2)Inhibition of acidification of the


    phagosome which reduces the activity of
    lysosyme e.g. legionella.
    3)Escape from phagosome into the
    cytoplasm e.g. Listeria.
    Pathogenesis
    C) Disease production by toxins, enzyme,
    invasion and inflammation:
    Toxins: Are either bacterial part or bacterial
    production, cause damage to host tissue or may
    interact with immune system and cause
    pathological effect.
    Two major types of toxins:
    a) Endotoxin
    b) Exotoxin.
    Pathogenesis

    Endotoxin: LPS or LOS, of the outer membrane


    components of Gram-negative bacteria.
    They are released after lysis of bacterial cell in
    vitro.
    Cause activation of macrophages and
    complement via alternative pathway.
    Results in release of cytokines and exert their
    biological effect.
    Pathogenesis

    Biological effects of endotoxin:


    •Activates Macrophage:
    IL-1 → fever.
    TNF → Fever and hypotension.
    Nitric oxide → Hypotension.
    Pathogenesis

    Biological effects of endotoxin:


    • Activates complement →
    C3a → Hypotension, edema.
    C5a → Neutrophil, chemotaxis.
    • Activates Hagement factor (XII) →
    Coagulation cascade →DIC.
    Pathogenesis

    • Exotoxin: Exotoxins are diffusible proteins


    secreted by bacteria.
    • Vary in their molecular structures,
    mechanism of secretion, biological function
    and immunological properties.
    Pathogenesis
    Features of Endotoxin & Exotoxin:
    Property Exotoxin Endotoxin

    Source Gram-positive& Gram-negative


    Gram-negative
    Chemistry Polypeptide LPS

    Location of genePlasmid Bacterial


    /bacteriophage chromosome
    Toxicity High(1μg is fatal) Low(100 μg fatal)
    Property Exotoxin Endotoxin

    Clinical effect Various Fever, shock, DIC

    Mode of action Various TNF, IL-1

    Antigenicity High Poor

    Vaccine Toxoids used in No


    vaccine
    Heat stability Destroyed at Stable at 100ºC
    60ºC
    Pathogenesis
    Mechanism of action of important exotoxins:
    Mechanism of action Exotoxin

    ADP ribosilation Diphtheria toxin, cholera


    toxin, pertussis toxin etc.

    Super antigen TSST, Staph. enterotoxin

    Protease Tetanus, Botulinum toxin,


    Anthrax toxin.
    Lecithinase Cl. Perfringes alpha toxin.
    Pathogenesis

    • Several important exotoxin:


    • Bacillus anthracis (Anthrax toxin):
    Edema Factor→ An adenylate cyclase → causes
    ↑ed level of cyclic AMP in phagocytes → ion-
    permeable pores in membranes.
    Lethal factor: Protease → cleaves phosphokinase,
    required for growth of cells.
    Protective antigen: Binds to cell surface.
    Pathogenesis
    • Bordetella pertussis toxin:
    Stimulates adenylate cyclase activity → causes
    ↑ed levels of CAMP →causes edema and also
    inhibits chemokine receptor.
    • Corynebacterium diphtheriae(Diphtheria
    toxin):
    ADP ribosylation of elongation factor-2 leads to
    inhibition of protein synthesis in target cells.
    Pathogenesis
    • Vibrio cholerae(Cholera enterotoxin):

    ADP ribosylation of G proteins→stimulates


    adenylate cyclase→increases cAMP
    →causes secretion of water and electrolytes.
    • Staph. Aureus (Toxic shock syndrome toxin):
    Acts on the vascular system causing fever,
    shock and inflammation.
    Pathogenesis
    • Clostridium botulinum(Botulinum toxin):

    Protease that degrade protein responsible for


    release of acetylcholine at neuromuscular
    synapses resulting in flaccid paralysis
    • Clostridium tetani(Tetanus toxin):
    Protease that inhibits release of inhibitory
    neurotransmitter glycine resulting in spastic
    type paralysis.
    Pathogenesis
    • Staphylococcus aureus(enterotoxin):
    Causes release of cytokines from lymphoid
    cells→stimulates enteric nervous system →
    activates vomiting center.
    • Shigella dysenteriae(Shiga toxin):
    Enzymatically cleaves rRNA resulting in
    inhibition of protein synthesis in susceptible
    cells.
    Pathogenesis

    Disease production by enzymes:


    Several enzymes secreted by bacteria play
    role in the pathogenesis e.g. collgenase,
    hyaluronidase, coagulase, protease,
    leukocidin, Streptokinase, DNAase etc.
    Pathogenesis
    Important water borne diseases:
    •Ingestion of drinking water: Salmonella,
    Shigella, Campylobacter, E. coli, Vibrio
    cholerae.
    •Ingestion of water while swimming:
    Leptospira interrogans.
    • Inhalation of water aerosol: Legionella
    pneumophila.

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