Microbial Mechanisms of Pathogenicity

Disease and Infection

  • Disease: A condition where normal body structure or functions are damaged or impaired (excluding injuries and disabilities).

  • Infection: Invasion and multiplication of a microbe in a host's tissues, leading to host damage.

  • Pathogen: An organism that can cause disease.

  • Diagnosis:

    • Signs: Objective evidence of disease noted by an observer.

    • Symptoms: Subjective evidence of disease noted by the patient.

    • Asymptomatic: No signs or symptoms of disease.

Diagnostic Challenges

  • Antibodies can persist in the blood after infection resolution, which may not indicate active disease.

  • Many microbes can cause similar signs and symptoms (e.g., influenza and COVID-19).

Classification of Diseases

  • Infectious Disease: Caused by the direct effect of a pathogen.

  • Communicable: Can be transmitted from person to person.

  • Contagious: Easily transmitted from person to person (e.g., measles).

  • Nosocomial: Acquired in a hospital or healthcare setting (Healthcare-Associated Infections or HAIs).

Periods of Disease

  • Incubation Period:

    • Pathogen multiplies in the host.

    • Insufficient pathogen particles to cause signs and symptoms.

    • Duration varies based on pathogen strength, host immune defenses, infection site/type, and infectious dose size.

  • Prodromal Period:

    • Pathogen multiplies.

    • Host experiences general symptoms (fever, soreness, inflammation).

  • Period of Illness:

    • Signs and symptoms are most severe.

  • Period of Decline:

    • Pathogen numbers decrease, and signs of illness decrease.

    • Secondary infections may occur due to weakened immune systems.

  • Period of Convalescence:

    • Patient returns to normal functions.

    • Possible permanent damage that the body cannot fully repair.

  • Infectiousness: Patients can be infectious throughout all stages, depending on the pathogen.

Contagious Period Examples

  • Infectious Mononucleosis:

    • Incubation: 30-50 days

    • Contagious: Onset of fever until fever is gone (7 days)

  • Meningitis (Bacterial):

    • Incubation: 2-10 days

    • Contagious: 7 days before symptoms until 24 hours on IV antibiotics in hospital

  • Meningitis (Viral):

    • Incubation: 3-6 days

    • Contagious: Onset of symptoms for 1-2 weeks

  • Mumps:

    • Incubation: 12-25 days

    • Contagious: 5 days before swelling until swelling is gone (7 days)

  • Pinkeye (Viral, without pus):

    • Incubation: 1-5 days

    • Contagious: Mild infection; staying home unnecessary

  • Pinkeye (Bacterial, with pus):

    • Incubation: 2-7 days

    • Contagious: Onset of pus until 1 day on antibiotic eyedrops

Types of Diseases

  • Acute Disease: Rapid onset, rapid recovery (e.g., influenza, diarrheal diseases).

  • Chronic Disease: Slow onset, long period of illness or recurring disease (e.g., arthritis, diabetes, tuberculosis).

  • Latent Disease: Pathogen goes dormant for extended periods with no active replication (e.g., herpes simplex virus HSV-1 or HSV-2).

Pathogenicity and Virulence

  • Pathogenicity: The ability of a microbial agent to cause disease.

  • Virulence: The degree to which an organism is pathogenic; a continuum from avirulent to highly virulent.

Primary vs. Opportunistic Infections

  • Primary Infections: Can cause disease regardless of the host's microbiota or immune system (e.g., enterohemorrhagic E. coli (EHEC) producing Shiga toxin).

  • Opportunistic Infections: Cause disease when host defenses are weakened (e.g., Staphylococcus epidermidis on catheters).

Stages of Pathogenesis

  • Four stages for successful pathogenesis: Exposure (contact), Adhesion (colonization), Invasion, and Infection.

Exposure

  • Mucosal Surfaces: Most important portals of entry (respiratory, gastrointestinal, and genitourinary tracts).

  • Parenteral Route: Through breaches in the skin and mucous membranes.

Placental Barrier

  • Most microbes cannot cross, but some can (TORCH infections).

  • TORCH Infections:

    • T: Toxoplasmosis (Toxoplasma gondii)

    • O: Other (Syphilis - Treponema pallidum, Chickenpox - Varicella-zoster virus, Hepatitis B virus, HIV, Fifth disease - Parvovirus B19)

    • R: Rubella (German measles - Togavirus)

    • C: Cytomegalovirus (Human herpesvirus 5)

    • H: Herpes (Herpes simplex viruses (HSV) 1 and 2)

Adhesion

  • Adhesion: Pathogenic microbes attach to host cells using adhesion factors.

  • Adhesins: Molecules on the pathogen's surface that bind to specific receptors on host cells.

  • Location:

    • Fimbriae

    • Capsules

    • Flagella

    • Spike proteins

Invasion

  • Virulence Factors: Determine the extent and severity of the disease.

    • Enhance the ability of bacteria to cause disease.

    • Include mechanisms for:

      • Invading (adhering/colonizing)

      • Overcoming host defenses

      • Producing toxins (exotoxins and endotoxins)

Infection

  • Infection: Successful multiplication of the pathogen.

    • Local: Confined to the portal of entry, small area.

    • Focal: Localized pathogen spreads to a secondary location.

    • Systemic: Infection disseminated throughout the body.

Virulence Factors

  • Bacterial exoenzymes and toxins.

  • Invasion often involves enzymes and toxins.

  • Pathogens may enter the bloodstream for systemic travel.

  • Presence of Microbes/Products in Blood:

    • Bacteremia: Bacteria in the blood (can be transient).

    • Septicemia: Bacteria multiplying in the blood.

    • Toxemia: Toxins in the blood.

    • Viremia: Viruses in the blood.

Exoenzymes

  • DNAses:

    • Break down DNA for escape and spreading through tissue.

    • Produced by Staph. aureus.

    • Degrade DNA from dead bacterial and host cells that can trap bacteria.

  • Phospholipases:

    • Degrade phospholipids of cell membranes.

    • Facilitate escape from phagosomes.

    • Cause lysis of red blood cells, white blood cells, and tissue cells.

Classes of Exoenzymes and Their Targets

  • Glycohydrolases:

    • Example: Hyaluronidase S in Staphylococcus aureus

    • Function: Degrades hyaluronic acid that cements cells together to promote spreading through tissues

  • Nucleases:

    • Example: DNAse produced by S. aureus

    • Function: Degrades DNA released by dying cells (bacteria and host cells) that can trap the bacteria, thus promoting spread

  • Phospholipases:

    • Example: Phospholipase C of Bacillus anthracis

    • Function: Degrades phospholipid bilayer of host cells, causing cellular lysis, and degrade membrane of phagosomes to enable escape into the cytoplasm

  • Proteases:

    • Example: Collagenase in Clostridium perfringens

    • Function: Degrades collagen in connective tissue to promote spread

Toxins

  • Virulence factors that cause tissue damage and assist in invasion.

  • Biological poisons.

  • Endotoxins:

    • Produced by Gram-negatives; present on the outer membrane (LPS).

    • Released upon cell lysis or binary fission.

    • LPS (Lipopolysaccharide): Lipid A triggers inflammation.

      • Low dose: Body can defend itself.

      • High dose: Excessive inflammatory response leading to shock.

      • Lipid A is the toxic component that promotes inflammation and fever.

  • Exotoxins:

    • Protein molecules produced by Gram-positive bacteria during growth and metabolism; secreted by live cells.

    • Specific in their action.

    • Interact with specific receptors on specific cells and damage the cells.

    • Very small doses can be lethal.

Specific Exotoxins

  • Botulinum Toxin:

    • Neurotoxin produced by Clostridium botulinum.

    • Inhibits muscle contraction, leading to muscle relaxation (protease cleaves proteins involved in neurotransmitter release).

  • Tetanus Toxin:

    • Neurotoxin produced by Clostridium tetani.

    • Causes spastic paralysis by inhibiting the release of chemicals that stop muscle contractions.

Membrane-Disrupting Toxins

  • Work by:

    • Forming Pores

    • Disrupting the phospholipid bilayer in host cell membranes

  • Include:

    • Hemolysins: Target cell membranes

    • Leukocidins: Target leukocytes (white blood cells)

Superantigens

  • Toxins that trigger excessive, nonspecific stimulation of immune cells to secrete cytokines (cytokine storm).

  • Result in:

    • Life-threatening high fevers

    • Low blood pressure

    • Multi-organ failure

    • Shock

    • Death

  • Example: Toxic Shock Syndrome Toxin (S. aureus).

Virulence Factors for Survival and Immune Evasion

  • Immune evasion is important for bacterial survival.

  • Capsule:

    • Used in adhesion.

    • Prevents ingestion by immune cells (makes bacteria larger and harder to digest).

Review Questions

  • What are some toxins that we talked about today - describe.

  • What is a virulence factor?