Microbial Mechanism of Pathogenicity

Chapter 15: Microbial Mechanism of Pathogenicity

Microbes, Host and Disease

  • Pathogenicity:

    • Defined as the ability of a microbe or pathogen to cause disease in a host.

  • Disease Process:

    • Virulence: Enhanced ability of a pathogen to cause infection leading to disease.

    • Virulence Factor:

    • A characteristic or trait of the pathogen that contributes to its harmfulness.

    • Examples of Virulence Factors:

      • Capsules

      • Toxins

      • Antigenic variation (e.g., changes in the composition of viral spikes).

Mechanisms of Pathogenicity

  • Various ways in which a microbe/pathogen can induce infectious disease.

  • Typical pathway of pathogenicity includes:

    • Number of invading microbes

    • Portal of entry

    • Adherence

    • Penetration/Evasion

    • Damage to host cells

    • Portal of exit

Portals of Entry

  • How do microbes enter a host?

    1. Mucous membranes

    2. Skin (broken)

    3. Parenteral Route

    • Bypasses the gastrointestinal (GI) tract.

    • Involves non-oral entry where pathogens are directly deposited into tissue or bloodstream, usually via injection.

    • Examples:

      • Intravenous (IV) entry through contaminated needles or insect bites (arthropod vector carrying a pathogen).

Numbers of Invading Microbes

  • A high number of pathogens can overwhelm host defenses leading to infection and disease.

  • Infectious Dose 50 (ID50):

    • A numerical value representing the number of pathogens required to make 50% of a population sick.

    • It measures the virulence of a microbe.

    • Infectious pathogens exhibit varying ID50’s:

    • Low ID50: Indicates high infectiousness (few microbes can cause significant illness).

    • High ID50: Indicates low infectiousness (requires many pathogens to invoke disease).

    • Serves as an indicator for the preferred portal of entry to cause disease.

    • Example: Bacillus anthracis (causes Anthrax)

    • Spore former with different ID50 through different routes:

      • Skin: 10-50 endospores (preferred route).

      • Inhalation: 10,000-20,000 endospores.

      • Injection: 250,000-1,000,000 endospores.

  • Some bacteria produce toxins that can result in host lethality.

  • Lethal Dose 50 (LD50):

    • Concentration of toxin necessary to kill 50% of a population.

    • Measures the potency of a toxin.

    • Toxigenic pathogens exhibit different LD50’s:

    • Low LD50: High lethality (very toxic).

    • High LD50: Low lethality (less toxic).

    • Example:

      • Pathogen #1: LD = 1000 mg/kg.

      • Pathogen #2: LD = 2 mg/kg (most lethal).

Adhesion Factors

  • Adherence (Adhesion):

    • The ability of pathogens to attach to host tissues or cells.

    • Pathogen attachment is essential to cause infection.

  • Bacterial Adhesins (Ligands):

    • Substances on the pathogen that bind to receptors on host cells.

    • Note: Do not confuse with antigenic determinants which bind to antibodies (Abs).

  • Types of Adhesins (Ligands) and Examples:

    1. Capsules:

    • Example: Streptococcus mutans found on teeth; has a large sugary capsule that contributes to cavity formation.

    1. Fimbriae:

    • Example: E. Coli O157:H7 (pathogenic strain).

    1. M Proteins:

    • Example: Streptococcus pyogenes.

    1. Opa Proteins:

    • Example: Neisseria gonorrhoeae.

    1. Hooks:

    • Example: Treponema pallidum.

How Pathogens Penetrate/Escape Host Defenses

  • Penetration Factors (Bacterial Enzymes):

    1. Coagulase:

    • Promotes blood clot formation, obstructing blood flow and hindering host defense access.

    • Pathogens can encase themselves within a clot.

    1. Kinase:

    • Dismantles blood clots surrounding pathogens, allowing spread through the body.

    1. Hyaluronidase:

    • Decomposes hyaluronic acid within connective tissues.

    1. Collagenase:

    • Decomposes collagen in connective tissues.

    1. IgA Protease:

    • Dismantles IgA antibodies (immunoglobulins which are proteins).

Evasion of Host Defenses

  • Survival Inside Phagocytes:

    • Pathogens may escape from the phagosome prior to lysosomal fusion.

    • Some pathogens prevent the fusion of lysosomes with phagosomes or resist lysosomal enzymes (e.g., pathogens with mycolic acid).

  • Antigenic Variation:

    • Immediate pathogens alter their surface antigens (antigenic determinants) through genetic mutations or recombination.

    • This is a significant virulence factor observed notably in viruses (e.g., spike changes in influenza virus, HIV).

Damage to Host Cells

  • Toxin (Antigen):

    • A poisonous substance produced by pathogens (particularly toxigenic bacteria).

    • Toxins may cause symptoms such as fever, cardiovascular issues, diarrhea, and sudden drops in blood pressure (shock).

  • Toxigenicity:

    • The ability of a pathogen to produce a toxin.

  • Toxemia:

    • The presence of toxins in the bloodstream.

  • Toxoid:

    • A chemically altered toxin that no longer possesses toxic properties.

    • On injection into the host, it prompts the immune response to produce antibodies (Abs).

  • Antitoxin:

    • An antibody against a toxin but not against the bacteria.

    • Usually administered to the host as artificial passive immunity.

Toxins

  • Some bacteria can generate toxins.

  • Often, it is the toxins (rather than the bacteria) that manifest disease symptoms.

Types of Toxins Produced by Bacteria

  1. Exotoxins (3 types)

  2. Endotoxins

  • Toxin production can involve bacterial plasmids that transport genes essential for toxin production.

  • Mechanism of Toxin Production:

    1. Resulting from lysogeny that includes phage conversion (virus involved).

    • Ordinary non-toxic cell becomes toxic due to viral genes.

    1. As a result of DNA transfer through conjugation.

    • Donor (toxigenic) transfers through pili to recipient (now toxigenic).

Toxins Acting as Immunogens

  • Immunogen:

    • Serves as an antigen that stimulates the immune system.

    • Examples include toxins, pathogens, dust, and pollen.

  • Strong vs. Weak Immunogens:

    • Strong Immunogen:

      • Effectively stimulates an immune response.

      • Produces antibodies without inducing fever.

      • Exception: Type I exotoxin (superantigens) can produce fever despite being protein toxins.

    • Weak Immunogen:

      • Poor stimulant of immune response.

      • Does not produce antibodies or fever.

      • Examples include lipid and polysaccharide toxins.

Exotoxins and Endotoxins

  • Exotoxins:

    • Secreted by living cells, primarily from gram-positive bacteria (and some negatives).

    • Composed of proteins (high toxicity) that result in a strong immune response with no fever, except for superantigens which can cause fever.

    • Neutralized by Antitoxin and exhibit a small LD50, indicating greater danger.

  • Endotoxins:

    • Part of the cell walls of dying gram-negative bacteria.

    • The lipid portion of LPS (lipopolysaccharide) is the toxin that induces fever.

    • Not neutralized by antitoxin and exhibit a large LD50, indicating less danger.

Types of Exotoxins

  1. Type I: Superantigens

    • Cause a very intense immune response through T-cell proliferation and cytokine release, leading to fever, nausea, and shock.

    • Example: Staphylococcal toxins.

  2. Type II: Membrane Disrupting (MD) Toxins

    • Cause the lysis of host cells by disrupting their cell membranes.

    • Mechanisms include forming channels in cell membranes or disrupting membrane components.

    • Examples: Leukocidins (destroy phagocyte leukocytes) and Hemolysins (destroy red blood cells).

  3. Type III: A-B Toxins

    • Composed of two components, A and B; the most prevalent type of exotoxin.

    • A-B toxins inhibit host cell protein synthesis.

    • Examples: Diphtheria toxin and neurotoxins.

Endotoxins and the Pyrogenic Response

  • Mechanism of Fever Induction by Endotoxins:

    1. Macrophages ingest gram-negative bacteria.

    2. Bacteria are degraded in a vacuole, releasing endotoxins (LPS) which trigger cytokine production.

    3. Cytokines are released into the bloodstream, traveling to the hypothalamus (the temperature control center of the brain).

    4. Cytokines induce the hypothalamus to reset the body's thermostat, resulting in fever.

Pathogenic Properties of Fungi

  • Certain fungal toxins can contaminate food supplies, provoke allergic reactions, and are even carcinogenic.

  • Example: Aflatoxin.

Pathogenic Properties of Parasitic Protozoa (Kingdom Protista)

  • Numerous protozoa consume host tissues.

  • They may cause damage to the intestinal lining and provoke diarrhea or dysentery (mucous bloody diarrhea).

  • Protozoa evade host defenses by:

    • Growing within phagocytes.

    • Utilizing antigenic variation as a virulence factor.

    • These pathogens change their external appearance, which can also occur in some parasites.

Pathogenic Properties of Parasitic Helminths

  • Helminths: refers to worms.

  • Generally exhibit low pathogenicity, as they utilize the host's nutrients or tissues without killing it (host survival is essential).

  • Their presence in the gastrointestinal (GI) tract in sizable quantities can hinder nutrient absorption, causing symptoms like fatigue and weight loss (due to anemia, as the worms consume host nutrients).

Portals of Exit: How Pathogens Leave

  • Pathogens typically exit through the same routes that they entered the body:

    • Respiratory Tract: Coughing and sneezing.

    • GI Tract: Through feces and saliva.

    • Skin.

    • Blood:

    • Via arthropods that bite.

    • Through needles and syringes.