Pathogenicity Notes

Establishing an Infection

• Initial Adhesion: Bacteria must first adhere to host tissues, but this alone isn't sufficient for establishing an infection.

Penetration of Barriers

• Skin:
  • The skin is a tough barrier, making penetration difficult.
  • Staphylococcus aureus typically enters through wounds or abrasions.
  • Yersinia pestis (bubonic plague) is introduced via insect bites.
• Mucous Membranes:
  • Penetration can occur through various mechanisms.
  • Salmonella uses a type three secretion system to inject proteins into host cells, causing cytoskeletal rearrangement and ruffle formation, leading to engulfment.
  • Helicobacter pylori produces urease, which raises the pH and liquefies the stomach lining, allowing the bacteria to penetrate the tissues.
    • Urease is a virulence factor because it neutralizes stomach acids.

Damage to the Host

• Mechanisms of Damage:
  • Direct damage by the bacterium's presence.
  • Toxin production directly harming host cells.
  • Indirect damage from the host's immune response.
• Examples:
  • Vibrio cholerae (cholera) produces a toxin (through lysogenic conversion) leading to severe diarrhea and dehydration, which also contaminates water supplies, facilitating spread.
  • Bordetella pertussis (whooping cough) produces a toxin that causes severe coughing, releasing the bacteria into the air.

Toxins: Exotoxins vs. Endotoxins

Exotoxins

• General Characteristics:
  • Always proteins.
  • Secreted or leak into tissues.
  • Act outside of the bacterium (exo = out).
  • Highly specific due to their three-dimensional shape.
  • Can be encountered through infection or consumption (e.g., in distended cans, potentially causing botulism).
  • Mostly heat-sensitive.
  • Can act locally or systemically.
  • Often fatal before an immune response can occur.
• Prevention/Treatment:
  • Toxoids: Inactivated toxins used in vaccines.
  • Antitoxins: Antibodies used to neutralize toxins.
• Types of Exotoxins:
  • Neurotoxins (target the nervous system, e.g., tetanus).
  • Enterotoxins (cause intestinal disturbance, e.g., E. coli Shiga toxin).
  • General cell-damaging toxins.
• Three Main Types: AB toxins, membrane-damaging toxins, super antigens.

AB Toxins

• Structure: Two parts: A (active) and B (binding).
  • A subunit: Toxic part, often an enzyme.
  • B subunit: Binds to specific cell receptors, determining the target cell type.
• Mechanism:
  • Toxin binds to the cell receptor via the B subunit.
  • Brought into the cell in a vacuole.
  • A subunit is released and exerts its toxic effect.
• Diphtheria Toxin:
  • Stops protein synthesis by interfering with ribosomes, leading to cell death.
  • Enters via the nose or mouth, causing a severe sore throat and respiratory distress.
• Tetanus and Botulism Toxins:
  • Interfere with the nervous system, but one leads to muscle contraction (tetanus), while the other leads to muscle relaxation (botulism).

Membrane-Damaging Toxins

• Mechanism: Disrupt plasma membranes, causing cell lysis.
• Hemolysins:
  • Made by Streptococcus pyogenes.
  • Lyse red blood cells (RBCs), visible as clearing zones on blood agar.
  • Bacteria use the contents of lysed RBCs for food.
• Clostridium perfringens:
  • Causes gas gangrene.
  • Rips apart phospholipids in the cell membrane.
  • Proteins insert into the plasma membrane, creating holes.

Super Antigens

• Mechanism:
  • Cause incorrect communication between cells of the immune system, specifically between a helper T cell and an antigen-presenting cell.
  • Bind nonspecifically to T cell receptors and MHC molecules, leading to overstimulation of the immune system.
  • Result in a massive release of cytokines (cytokine storm).
• Toxic Shock Syndrome:
  • Caused by Staphylococcus aureus and Streptococcus.
  • Leads to a precipitous drop in blood pressure.
  • Examples are Streptococcus and Staphylococcus, which are good at causing disease because they have virulence factors.

Endotoxins

• General Characteristics:
  • Part of the bacterial cell, specifically lipopolysaccharide (LPS) in the gram-negative cell wall.
  • Cause a strong inflammatory response.
  • Heat-stable; cooking does not eliminate them.
• Mechanism:
  • Systemic presence leads to a massive immune response and shock.
  • Activation of the immune system causes damage.
• Effect: Triggers an immune system effect, usually inflammation.

Comparison: Endotoxins vs. Exotoxins

• LD_{50} (Lethal Dose 50): The amount required to kill 50% of those exposed. A low LD50 indicates high toxicity.

Viral Pathogenicity

• Attachment: Viruses attach to specific target cells via receptors.
• Immune Evasion:
  • Interferon Interference: Block expression or enzymes used to fight off viruses.
  • Gene Expression Manipulation: Interfere with the host's gene expression.
  • Syncytia Formation: Cause cells to fuse, protecting the viruses from the immune system (e.g., RSV).
  • Antigenic Variation: Constantly change surface antigens due to high mutation rates (especially in RNA viruses), making it difficult for the immune system to recognize and remember the viruses.
  • Inhibition of Cell Death: Prevent the presentation of viral antigens, stopping the body from targeting infected cells for cell death.

Eukaryotic Pathogenicity

Fungi

• General Characteristics:
  • Mostly live on decaying matter.
  • Primarily opportunistic pathogens in humans.
• Superficial Infections:
  • Affect hair, skin, and nails.
  • Produce keratinase to break down keratin.
• Candida:
  • Normal microbiota on mucous membranes but can cause disease in immunocompromised individuals or those on antibiotics.
• Dimorphic Fungi:
  • Cause serious infections in immunocompromised individuals.
  • Infect deep within the lungs and can spread to other areas.
• Mycotoxins: Fungi can produce toxins that cause disease.

Protozoans and Helminths

• Immune Evasion:
  • Live in the intestines or enter via arthropods, residing inside host cells.
  • Antigenic variation: change surface antigens to avoid immune detection.
• Damage Mechanisms:
  • Nutrient consumption, blockage of intestines (helminths).
  • Red blood cell lysis (Plasmodium).
  • Immune response itself causes damage (similar to endotoxins).