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Microbiology

Organism Pathogenicity

This section covers the organism pathogenicity of BSL-3 pathogens and Select Agents, focusing on their etiology (cause), transmission, and virulence mechanisms. This is crucial for understanding the threat posed by these organisms and developing effective prevention and treatment strategies

Understanding Pathogenicity

  • Pathogenicity Defined: The ability of a microorganism to cause disease. It encompasses the mechanisms by which the organism causes harm to the host
  • Key Components of Pathogenicity
    • Etiology: The cause of the disease, specifically the microorganism responsible
    • Transmission: The mechanisms by which the organism spreads from one host to another (or from a reservoir to a host)
    • Virulence Mechanisms: The specific factors and processes that enable the organism to cause disease. These include:
      • Adherence: The ability to attach to host cells
      • Invasion: The ability to penetrate and spread within host tissues
      • Toxin Production: The production of toxins that damage host cells or disrupt normal physiological processes
      • Immune Evasion: Mechanisms that allow the organism to evade the host’s immune response

Pathogenicity of Specific BSL-3 Pathogens and Select Agents

Here’s a breakdown of the pathogenicity for the key organisms discussed previously:

Bacillus anthracis (Anthrax)

  • Etiology: Bacillus anthracis is a Gram-positive, spore-forming bacterium
  • Transmission
    • Cutaneous Anthrax: Through contact with spores that enter the skin through cuts or abrasions
    • Inhalational Anthrax: Through inhalation of spores
    • Gastrointestinal Anthrax: Through ingestion of contaminated meat (rare)
  • Virulence Mechanisms
    • Spore Formation: Spores are highly resistant to environmental conditions and can survive for long periods. Spores germinate upon entering a susceptible host
    • Capsule: Composed of poly-D-glutamic acid, the capsule protects the bacterium from phagocytosis by immune cells
    • Toxins: Produces two main toxins:
      • Protective Antigen (PA): Binds to host cell receptors and facilitates the entry of the other two toxins
      • Lethal Factor (LF): Disrupts cell signaling pathways, leading to cell death
      • Edema Factor (EF): Increases intracellular cyclic AMP (cAMP) levels, causing edema (swelling)
    • Pathogenesis: Spores germinate within the host, and the bacteria multiply. The toxins cause tissue damage, edema, and potentially systemic infection, leading to severe illness or death if untreated

Yersinia pestis (Plague)

  • Etiology: Yersinia pestis is a Gram-negative, non-motile bacterium
  • Transmission
    • Bubonic Plague: Transmitted to humans through the bite of an infected flea (typically from rodents)
    • Pneumonic Plague: Transmitted through inhalation of respiratory droplets from an infected person or animal (e.g., cats)
  • Virulence Mechanisms
    • Type III Secretion System (T3SS): A molecular syringe that injects effector proteins (Yops) into host cells
    • Yops
      • YopH: Disrupts the cytoskeleton of phagocytes, inhibiting phagocytosis
      • YopE: Disrupts the cytoskeleton of endothelial cells, causing vascular permeability
      • YopJ: Interferes with the host’s inflammatory response
    • Capsule: Protects against phagocytosis
    • Pathogenesis: The bacteria multiply in the lymph nodes (bubonic plague) or lungs (pneumonic plague). The Yops disrupt the host’s immune response, leading to inflammation, tissue damage, and potentially systemic infection, resulting in severe illness or death if untreated

Brucella spp. (Brucellosis)

  • Etiology: Bacteria belonging to the genus Brucella (e.g., Brucella melitensis, Brucella abortus, Brucella suis) are Gram-negative coccobacilli
  • Transmission
    • Contact: Through direct contact with infected animals (e.g., cattle, sheep, goats, pigs) or their products (e.g., meat, milk)
    • Ingestion: Through consumption of unpasteurized dairy products or contaminated meat
    • Inhalation: Through inhalation of aerosols containing the bacteria
  • Virulence Mechanisms
    • Intracellular Survival: Brucella spp. can survive and multiply within phagocytic cells (e.g., macrophages), allowing them to evade the host’s immune response
    • Lipopolysaccharide (LPS): The structure of Brucella LPS is less immunogenic than that of other Gram-negative bacteria, contributing to immune evasion
    • Pathogenesis: The bacteria enter the host through the mucous membranes or skin. They are taken up by phagocytes and spread throughout the body, leading to chronic inflammation, fever, and other systemic symptoms

Francisella tularensis (Tularemia)

  • Etiology: Francisella tularensis is a Gram-negative coccobacillus
  • Transmission
    • Tick Bites: Most common mode of transmission (e.g., from ticks, deer flies, or other arthropods)
    • Direct Contact: Through contact with infected animals (e.g., rabbits, rodents)
    • Inhalation: Through inhalation of aerosols containing the bacteria (pneumonic tularemia)
    • Ingestion: Through ingestion of contaminated water or meat
  • Virulence Mechanisms
    • Intracellular Survival: F. tularensis can survive and multiply within phagocytes, allowing them to evade the host’s immune response
    • Capsule: May contribute to resistance to phagocytosis
    • Pathogenesis: The bacteria enter the host through the skin (ulceroglandular tularemia), lungs (pneumonic tularemia), or other routes. They are taken up by phagocytes and spread throughout the body, leading to a variety of symptoms, including fever, lymph node swelling, and pneumonia, resulting in severe illness or death if untreated

Burkholderia mallei (Glanders)

  • Etiology: Burkholderia mallei is a Gram-negative bacillus
  • Transmission: Primarily infects horses, donkeys, and mules; can be transmitted to humans
    • Contact: Through direct contact with infected animals or their contaminated secretions (e.g., nasal discharge, pus)
    • Inhalation: Through inhalation of aerosols
  • Virulence Mechanisms
    • Adherence: B. mallei adheres to host cells
    • Invasion: Can invade host cells
    • Type III Secretion System (T3SS): Delivers effector proteins that disrupt host cell function
    • Pathogenesis: Causes glanders, a disease that can manifest in localized (e.g., skin ulcers, nasal discharge) or systemic forms. The infection can lead to pneumonia, sepsis, and death if untreated

Burkholderia pseudomallei (Melioidosis)

  • Etiology: Burkholderia pseudomallei is a Gram-negative bacillus
  • Transmission
    • Contact: Through direct contact with contaminated soil or water
    • Inhalation: Through inhalation of aerosols
    • Ingestion: Through ingestion of contaminated water
  • Virulence Mechanisms
    • Adherence: B. pseudomallei adheres to host cells
    • Invasion: Can invade host cells
    • Type III and Type VI Secretion Systems (T3SS & T6SS): Delivers effector proteins that disrupt host cell function
    • Capsule: Protects against phagocytosis
    • Pathogenesis: Causes melioidosis, a disease that can manifest in localized (e.g., skin ulcers, pneumonia) or systemic forms. The infection can lead to pneumonia, sepsis, and death if untreated

Implications for Laboratory Practice

  • Risk Assessment: Understanding the pathogenicity of these organisms helps in assessing the risks associated with handling them in the laboratory
  • Biosafety Measures: Pathogenicity information informs the implementation of appropriate biosafety measures, including:
    • BSL-3 containment
    • Use of appropriate PPE
    • Safe work practices
  • Diagnostic Testing: Knowledge of virulence mechanisms helps in the development of effective diagnostic tests
  • Treatment and Prevention: Understanding pathogenicity is crucial for developing effective treatments and prevention strategies (e.g., vaccines, antibiotics)
  • Surveillance: Understanding the transmission routes and epidemiology of these organisms is critical for effective surveillance efforts

Key Terms

  • Pathogenicity: The ability of a microorganism to cause disease
  • Etiology: The cause of a disease, specifically the microorganism responsible
  • Transmission: The mechanisms by which a microorganism spreads from one host to another (or from a reservoir to a host)
  • Virulence: The degree of pathogenicity of a microorganism, often quantified by its ability to cause disease or the severity of the disease it causes
  • Virulence Mechanisms: The specific factors and processes that enable a microorganism to cause disease. These include adherence, invasion, toxin production, and immune evasion
  • Adherence: The ability of a microorganism to attach to host cells
  • Invasion: The ability of a microorganism to penetrate and spread within host tissues
  • Toxin: A poisonous substance produced by a microorganism that can damage host cells or disrupt normal physiological processes
  • Capsule: A protective layer surrounding some bacteria that helps them evade the host’s immune response
  • Immune Evasion: Mechanisms that allow a microorganism to evade the host’s immune response
  • Spore: A dormant, highly resistant form of a bacterium, such as Bacillus anthracis, that can survive harsh environmental conditions
  • Type III Secretion System (T3SS): A molecular syringe used by some bacteria to inject effector proteins directly into host cells
  • Type VI Secretion System (T6SS): A molecular syringe used by some bacteria to inject effector proteins directly into host cells
  • LPS (Lipopolysaccharide): A component of the outer membrane of Gram-negative bacteria that can act as a potent immunostimulant, but can also contribute to immune evasion in some species
  • Phagocytosis: The process by which a cell (e.g., a macrophage) engulfs and destroys a foreign particle (e.g., a bacterium)
  • Aerosol: A suspension of fine particles (e.g., liquid droplets or solid particles) in the air. Aerosol transmission is a significant concern for some BSL-3 pathogens
  • Zoonotic Disease: A disease that can be transmitted from animals to humans