Organism pathogenicity

This section explores the pathogenicity of Mycobacteria and Nocardia, focusing on how these organisms cause disease. We’ll cover the etiology (causative agents), transmission routes, and the virulence mechanisms that enable them to establish infection and cause harm

General Principles

Opportunistic Pathogens: Many Mycobacteria and Nocardia species are opportunistic pathogens, meaning they primarily cause disease in individuals with weakened immune systems or underlying lung conditions
Intracellular Survival: A key feature of many Mycobacteria and Nocardia is their ability to survive and multiply within host cells, particularly macrophages
Chronic Infections: Infections caused by these organisms are often chronic and can be difficult to eradicate
Environmental Reservoirs: Many of these organisms are found in the environment (soil, water), making complete eradication difficult

Mycobacterium tuberculosis

Etiology: Mycobacterium tuberculosis is the causative agent of tuberculosis (TB). It is a slow-growing, aerobic, acid-fast bacillus
Transmission: Primarily through airborne droplets produced when people with active pulmonary TB cough, sneeze, speak, or sing. Prolonged close contact is usually required for transmission
Virulence Mechanisms
- Cell Wall Components: The unique cell wall of M. tuberculosis, rich in mycolic acids, contributes to its virulence by:
  - Protecting the organism from phagocytosis by macrophages
  - Resisting killing by reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by macrophages
  - Inducing granuloma formation, which can protect the bacteria from the immune system but also contribute to tissue damage
- Cord Factor (Trehalose Dimycolate): A glycolipid found in the cell wall that:
  - Inhibits macrophage migration
  - Induces granuloma formation
  - Contributes to the characteristic “cording” appearance of M. tuberculosis colonies
- ESAT-6 and CFP-10: Secreted proteins that:
  - Inhibit macrophage activation
  - Promote bacterial survival within macrophages
  - Contribute to the pathogenesis of TB
- Latency: M. tuberculosis can establish a latent infection, in which the bacteria are dormant and cause no symptoms. Latent TB can reactivate later in life, especially in individuals with weakened immune systems
- Immune Evasion: M. tuberculosis employs various strategies to evade the host immune response, including:
  - Inhibiting phagosome-lysosome fusion in macrophages
  - Modulating cytokine production
  - Suppressing T cell responses

Mycobacterium avium complex (MAC)

Etiology: A group of closely related mycobacteria, primarily Mycobacterium avium and Mycobacterium intracellulare
Transmission: Primarily through inhalation or ingestion of contaminated water or soil. Person-to-person transmission is rare
Virulence Mechanisms
- Cell Wall Components: Similar to M. tuberculosis, the cell wall of MAC contributes to its virulence by:
  - Protecting the organism from phagocytosis
  - Resisting killing by macrophages
- Biofilm Formation: MAC can form biofilms in water systems, which can protect the bacteria from disinfectants and contribute to their persistence in the environment
- Intracellular Survival: MAC can survive and multiply within macrophages, leading to disseminated infections in immunocompromised individuals
- Secretion Systems: MAC utilizes secretion systems to export proteins that contribute to its virulence
- Glycopeptidolipids (GPLs): GPLs are surface glycolipids that contribute to biofilm formation, macrophage interactions and serum resistance

Mycobacterium kansasii

Etiology: Mycobacterium kansasii is a slow-growing, acid-fast bacillus
Transmission: Likely through inhalation of contaminated water droplets. Person-to-person transmission is rare
Virulence Mechanisms
- Cell Wall Components: Similar to other mycobacteria, the cell wall of M. kansasii contributes to its virulence
- Intracellular Survival: M. kansasii can survive and multiply within macrophages
- Secretion Systems: M. kansasii utilizes secretion systems to export proteins that contribute to its virulence
- Photochromogenicity: The production of a yellow pigment when exposed to light may contribute to virulence

Mycobacterium marinum

Etiology: Mycobacterium marinum is a slow-growing, acid-fast bacillus
Transmission: Through direct inoculation of the bacteria into the skin, often through cuts or abrasions exposed to contaminated water (aquariums, swimming pools)
Virulence Mechanisms
- Granuloma Formation: M. marinum induces granuloma formation in the skin
- Intracellular Survival: M. marinum can survive and multiply within macrophages
- Secretion Systems: M. marinum utilizes a type VII secretion system (ESX-1) to export proteins that contribute to its virulence
- Temperature-Sensitive Growth: M. marinum grows best at lower temperatures (30-32°C), which may explain its predilection for skin infections

Mycobacterium abscessus

Etiology: Mycobacterium abscessus is a rapidly growing mycobacterium
Transmission: Through direct contact with contaminated water or soil, or through contaminated medical devices. Person-to-person transmission is rare
Virulence Mechanisms
- Rapid Growth: M. abscessus grows more rapidly than other mycobacteria, allowing it to establish infection quickly
- Biofilm Formation: M. abscessus can form biofilms, which protect it from antibiotics and disinfectants
- Intrinsic Antibiotic Resistance: M. abscessus is intrinsically resistant to many antibiotics, making treatment challenging
- Cell Wall Components: The cell wall of M. abscessus contains glycopeptidolipids (GPLs) that contribute to its virulence
- Secretion Systems: M. abscessus utilizes secretion systems to export proteins that contribute to its virulence

Nocardia spp.

Etiology: Nocardia are aerobic, gram-positive, branching filamentous bacteria that are weakly acid-fast
Transmission: Primarily through inhalation of dust or soil containing Nocardia, or through direct inoculation into the skin
Virulence Mechanisms
- Catalase and Superoxide Dismutase: These enzymes protect Nocardia from killing by reactive oxygen species (ROS) produced by phagocytes
- Cord Factor: Similar to M. tuberculosis, Nocardia produces cord factor, which contributes to its virulence
- Intracellular Survival: Nocardia can survive and multiply within macrophages
- Proteases: Nocardia produces proteases that can degrade host tissues
- Adherence Factors: Nocardia possesses adherence factors that allow it to attach to host cells

Key Terms

Pathogenicity: The ability of an organism to cause disease
Etiology: The cause or origin of a disease or abnormal condition
Transmission: The way a disease is spread from one person or source to another
Virulence Mechanisms: Factors that enable a pathogen to establish infection and cause harm
Opportunistic Pathogen: An organism that causes disease primarily in individuals with weakened immune systems
Intracellular Survival: The ability of an organism to survive and multiply within host cells
Chronic Infection: An infection that persists for a long period of time
Cell Wall: The outer layer of a bacterial cell that provides structure and protection
Mycolic Acids: Long-chain fatty acids found in the cell walls of mycobacteria
Phagocytosis: The process by which cells engulf and ingest other cells or particles
Macrophages: Immune cells that engulf and destroy foreign particles and pathogens
Reactive Oxygen Species (ROS): Chemically reactive molecules containing oxygen that can damage cells
Reactive Nitrogen Species (RNS): Chemically reactive molecules containing nitrogen that can damage cells
Granuloma: A mass of immune cells that forms when the body attempts to wall off substances it perceives as foreign but cannot eliminate
Cord Factor (Trehalose Dimycolate): A glycolipid found in the cell walls of mycobacteria and Nocardia that contributes to their virulence

Resistance Markers

Procedures