PATHOGENICITY

Microbe vs. Host

§   To cause disease a microbe must:

§   Gain access to host

§   Evade host defenses

§   Damage host tissues

Steps to Disease

§   Gain entry through portal or host

§   Adherence

§   Invasion

§   Must protect itself from host defense system while invading tissues (penetrating)

§   Damage

Portals of Entry for Pathogens

§    Mucous membranes

§    Respiratory tract

§  Easiest portal to enter and most commonly infected

§  Many microbes travel in aerosols which we breath

§  Ex. Cold, TB, Influenza, Smallpox, Pneumonia

§    Gastrointestinal tract

§  Through food, water and dirty fingers

§  Must overcome low pH of the gut

§  Ex. Amoebic dysentary, Hepatitis, Shigellosis

§    Genitourinary tract

§  For STDs

§  Broken (parenteral route) or unbroken membranes (depends on the microbe)

§  Ex. HIV, Genital warts, Herpes, Syphilis

Portals of Entry for Pathogens

§  Skin

§   Impenetrable (for the most part)

§  Not true if skin is broken

§  Hookworm larvae can bore through skin

§   Hair follicles and sweat gland ducts (many of which have antimicrobial oils associated with them)

§   Some fungi (Example: ringworm) can infect actual skin.

§   Parenteral route:  When there is a break in the skin, the skin can be penetrated

§  Preferred portal of entry

§   Many microorganisms have to enter in a specific way and in a certain place to cause disease.

§  Ex. Vibrio cholerae infects the GI tract; therefore, rubbing an infected oyster on a wound will not cause cholera

Number of Invading Microbes

§   ID₅₀:  Number of microbes in a dose that causes infection in 50% of the organisms infected

§   LD₅₀:  Number of microbes in a dose that kill 50% of the organisms infected in a sample

§   The LD₅₀ and ID₅₀ change for different circumstances

Bacillus Anthracis

ADHERENCE

§     First step in pathogenicity

§     Microbes must attach to a surface

§     Adhesins or ligands of microbe attach to receptor in host

§    Adhesins or ligands

§   Mostly glycoproteins or lipoproteins in cell wall, or sugars associated with glycocalyx, or fimbriae

§   Vary from microbe to microbe

§    Receptors

§   Usually sugars

§   Vary from host to host

§    Example - Streptococcus mutans (causes tooth decay)

§   Converts glucose to dextran (used in glycocalyx)

§   Actinomyces attaches to glycocalyx of S. mutans by fimbriae

§     Biofilm

§     Tapered end

§    Treponema pallidum

Invasion:  Penetration of Host Defenses

§   Capsules (glycocalyx)

§   Even though a microbe has a capsule doesn’t mean it is a pathogen and not all pathogens have a capsule

§   Adherence and protection from phagocytosis (immune system defense)

§   Often a key role in virulence

§   Ex. S. pneumoniae is only virulent when capsule present

Invasion:  Penetration of Host Defenses

• Cell wall
  • Some bacteria have cell walls that contribute to virulence
  • M protein
    • Used for attachment and resistance to phagocytosis by WBCs
    • Ex. S. pyogenes
  • Mycolic acid (waxy lipid)
    • Resist digestion by phagocytes
    • Ex. Mycobacterium tuberculosis
  • Opa protein (outer membrane)
    • Inhibits T cells
    • Ex. Neisseria gonorrhoeae

Invasion:  Protection from Host Defenses

§    Enzymes

§    Coagulases

§  Causes blood clots

§  Clots help to protect the microbe from host defenses by surrounding it

§  Ex. Boils caused by Staphylococci

§    Kinases

§  Dissolves fibrin clots which the host may form to isolate the pathogens—helps them escape from host defense

§  Staphylococcus uses staphylokinase

§    Hyaluronidase

§  Dissolves hyaluronic acid which is used to keep host cells togetheràblackening

§  Ex. Gangrene caused by Clostridium

Invasion:  Protection from Host Defenses

§    Enzymes (continued)

§    Collagenase

§  Breaks down collagen (connective tissue)

§  Helps in spreading

§    IgA proteases

§  IgAàan antibody that the host produces as a defense against invader

§  Some organisms produces IgA proteases, which destroy these antibodies

§  N. meningitidis

Invasion:  Protection from Host Defense

§   Antigenic variation

§   Antigens on surface of pathogen are recognized by host antibodies and defense cells

§   Some pathogens can change the proteins (antigens) on their cell surface to trick the host

§   Ex. Influenza virus

Penetration into Cytoskeleton of Host

§   Cytoskeleton

§   Actin

§   Invasins are enzymes that rearrange actin filaments

§   Example

§  Salmonella

Steps to Disease

§   Gain entry through portal

§   Adherence

§   Invasion

§   Must protect itself from host defense system while invading tissues (penetrating)

§   Damage

DAMAGE

§   Four Methods

§   Using Host’s nutrients

§   Direct damage around where invasion occurred

§   Toxins

§  Poisonous substances that are produced by pathogens (primary factor in pathogenesis)

§  Toxigenicity

§  Toxemia

§   Hypersensitivity

§  Immune system over reacts

DAMAGE

§    Host’s nutrients

§    Iron

§  Typically not available to pathogens

§   Hemoglobin, transferrin

§  Pathogen secretes siderophores to use host's iron

§  Pathogen may secrete toxins to help get iron

§    Direct Damage

§  Metabolism and production of waste in host

§  Multiplication

Endotoxins

Exotoxin

EXOTOXINS

§    3 categories of toxins

§    A-B toxins

§    Membrane disrupting toxins

§    Superantigens

§    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

Exotoxins

§   A-B toxins

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. Stretococci (streptolysin)

SUPERANTIGENS

§   Invoke very strong immune response

§   T cells

§   Release lots of cytokines which can cause severe symptoms

§   Ex. Staphylococci and food poisoning toxins

Another Way to Classify Exotoxins

§   Cardiotoxins

§   Neurotoxins

§   Enterotoxins

§   Cytotoxin

§   Hepatotoxin

§   Leukotoxin

More Important Exotoxin Examples

§    Botulinum toxin (Clostridium botulinum)--botulism

§    A-B Neurotoxin

§    Prevents transmission of signal from nerve cell to muscle cell at NMJ (inhibits release of acetylcholine)

§    Tetanus toxin (Clostridium tetani)--tetanus

§    A-B Neurotoxin that goes to central nervous system

§    Prevents inhibition of random contractions by muscles

§    Cholera toxin (Vibrio cholera)—cholera

§    A-B toxin enterotoxin

§  “A” induces cyclic AMP formation from ATP

§  Causes discharge of many fluids and electrolytes from intestine

§  Very heat sensitive

ENDOTOXIN

§    Problems with antibiotic treatment

§    Lysing cells

§    Cause macrophage to release high levels of cytokines

§    General Effects

§    Disseminated intravascular clotting

§  Endotoxins activate blood clotting proteins which blocks capillaries

§    Septic Shock:  loss of blood pressure due to bacteria (endotoxic shock)

§  Macrophages release TNF (tumor necrosis factor) when they attack some Gram – cells

§  TNF binds to many tissues of host and may cause

§   Damage to blood capillaries (loss of water and decrease in BP)

§   Damage to blood-brain barrier (leading to infection of CNS)

§    Extreme pyrogenic response

Pyrogenic Response

§    Macrophage ingestion and release of endotoxin from bacteria

§    Release of interleukin-1(pyrogens) in bloodstream

§    Interleukin-1 to hypothalmus and production of prostaglandins

§    Resetting of bodies thermostat à Fever

ENDOTOXINS

§   Test for endotoxins

§   Limulus amoebocyte lysate assay (LAL)

§  Horseshoe crab amoebocytes has lysates that cause clotting in the presence of endotoxins

Viruses

§    Viruses

§    Can penetrate and grow inside of cells where host defense cannot get them

§    Cytopathic effects

§  Cell death by

§   Multiplying viruses

§   Inhibition of DNA, RNA or protein synthesis

§   Effects on permeability of membrane

§  Cytocidal vs. Noncytocidal effects

§   Macromolecular synthesis to stop

§   Lysosome leaking = destruction of organelles

§   Inclusion bodies (virus parts)

§   Syncytium (fusing of cells)

§   Host cell function

§   Interferons (protects uninfected cells)

§   Antigenic changes on cell surface

§   Chromosomal breaks

§   Contact inhibition

Cytopathic Effects of Viruses

Pathogenic Properties of Fungi

§    Fungal waste products may cause symptoms.

§    Chronic infections provoke an allergic response.

§    Proteases

§    Candida, Trichophyton

§    Aflatoxin

§    Aspergillus

Pathogenic Properties of Algae

§   Paralytic shellfish poisoning

§   Dinoflagellates

Portals of Exit

§    Respiratory tract

§    Coughing and sneezing

§    Gastrointestinal tract

§    Feces and saliva

§    Genitourinary tract

§    Urine and vaginal secretions

§    Skin

§    Blood

§    Biting arthropods and needles or syringes

Mechanisms of Pathogenicity