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Microbiology

Organism Pathogenicity

Understanding the pathogenicity of the organisms that cause CSF infections is crucial for clinical microbiology. It is essential for clinicians to diagnose, treat, and prevent these serious infections. Pathogenicity is the ability of a microorganism to cause disease, and depends on the microbe’s capacity to:

  1. Colonize: a host
  2. Invade: tissues
  3. Evade: the host’s immune defenses
  4. Produce: toxins or other harmful substances

Organism Pathogenicity in Cerebrospinal Fluid Infections

Streptococcus pneumoniae

  • Etiology: Gram-positive, lancet-shaped diplococci
  • Transmission: Respiratory droplets
  • Virulence Mechanisms
    • Capsule: The key virulence factor. Polysaccharide capsule protects against phagocytosis
    • Adhesins: Facilitate attachment to respiratory epithelial cells
    • Pneumolysin: A pore-forming toxin that damages host cells
    • IgA Protease: Degrades host antibodies
  • Pathogenicity
    • Causes pneumococcal meningitis, characterized by:
    • Severe inflammation of the meninges
    • Rapidly progressive with high morbidity
    • High mortality rates if untreated
    • Varying degrees of neurological sequelae
  • Pathogenesis: Entry into the CNS, via the bloodstream, is common after respiratory tract colonization

Haemophilus influenzae

  • Etiology: Gram-negative coccobacilli or pleomorphic rods
  • Transmission: Respiratory droplets
  • Virulence Mechanisms
    • Capsule: Primarily type b H. influenzae (Hib). Polysaccharide capsule protects against phagocytosis
    • Adhesins: Facilitate attachment to host cells
    • Endotoxin (LPS): Triggers inflammation
  • Pathogenicity
    • H. influenzae type b is the major cause of meningitis in children (before vaccination)
    • Causes bacterial meningitis
    • Characterized by:
    • Rapidly progressive inflammation of the meninges
    • Can result in severe neurological sequelae
    • Mortality rate
  • Pathogenesis: Colonization, followed by invasion of the bloodstream, and subsequent spread to the CNS

Neisseria meningitidis

  • Etiology: Gram-negative diplococci (kidney bean-shaped)
  • Transmission: Respiratory droplets
  • Virulence Mechanisms
    • Capsule: Protects against phagocytosis; helps with serum resistance
    • Adhesins: Promote attachment to host cells
    • Endotoxin (LPS): Triggers inflammation and sepsis
    • Outer Membrane Proteins: Involved in adherence and immune evasion
  • Pathogenicity
    • Causes meningococcal meningitis, characterized by
    • Highly contagious
    • Rapidly progressive with high mortality if untreated
    • Can also cause sepsis
    • Often outbreaks
  • Pathogenesis: Entry into the bloodstream and spread to the meninges

Escherichia coli

  • Etiology: Gram-negative rods
  • Transmission: Fecal-oral route
  • Virulence Mechanisms
    • Adhesins: Fimbriae and other surface structures facilitate attachment to host cells
    • Capsule: Protects against phagocytosis
    • Endotoxin (LPS): A potent inflammatory stimulus, especially important in neonatal infections
  • Pathogenicity
    • A major cause of neonatal meningitis
    • Often associated with E. coli strains that possess specific virulence factors (e.g., K1 capsule)
    • High mortality and can lead to neurological sequelae
  • Pathogenesis: Neonatal meningitis often occurs secondary to sepsis, and the infection spreads from the bloodstream to the CNS

Listeria monocytogenes

  • Etiology: Gram-positive, short rods or coccobacilli
  • Transmission: Ingestion of contaminated food (e.g., deli meats, soft cheeses)
  • Virulence Mechanisms
    • Internalin: Surface protein promotes invasion of host cells
    • Listeriolysin O (LLO): A pore-forming toxin that allows the bacteria to escape from phagosomes
    • ActA: Promotes actin-based motility
  • Pathogenicity
    • Causes listeriosis. Can cause meningitis, particularly in:
      • Pregnant women
      • Neonates
      • Immunocompromised individuals
    • L. monocytogenes is an intracellular pathogen
    • Can cross the blood-brain barrier
  • Pathogenesis: Ingestion, invasion of the bloodstream, and spread to the CNS

Enterobacteriaceae (Other than E. coli)

  • Etiology: Gram-negative rods
  • Transmission: Various (e.g., healthcare-associated, contaminated food)
  • Virulence Mechanisms
    • Capsule: Protects against phagocytosis
    • Adhesins: Facilitate attachment to host cells
    • Endotoxin (LPS): Triggers inflammation
    • Siderophores: Produce siderophores to acquire iron
  • Pathogenicity
    • Can cause nosocomial meningitis, particularly in the setting of:
      • Hospitalization
      • Invasive procedures
      • Compromised immune systems
    • High mortality if not treated
  • Pathogenesis: Often associated with bloodstream infections and spread to the CNS

Staphylococcus aureus

  • Etiology: Gram-positive cocci in clusters
  • Transmission: Direct contact (skin, wounds), contaminated medical devices, airborne droplets
  • Virulence Mechanisms
    • Adherence: Surface proteins (e.g., Protein A, fibronectin-binding proteins) facilitate attachment to host tissues and medical devices
    • Invasion: Produces enzymes (e.g., coagulase, hyaluronidase) to invade tissues
    • Immune Evasion: Produces protein A, which binds to antibodies and prevents opsonization and phagocytosis. Produces catalase to inactivate reactive oxygen species
    • Toxins: Produces a wide array of toxins, including
      • Cytotoxins: (e.g., hemolysins) damage host cells
      • Superantigens: (e.g., toxic shock syndrome toxin-1 (TSST-1), enterotoxins) cause massive immune activation, leading to shock and organ failure
      • Exfoliative toxins: Cause skin blistering (scalded skin syndrome)
    • Antibiotic Resistance: Frequently develops resistance to antibiotics (e.g., methicillin-resistant S. aureus (MRSA))
  • Pathogenicity
    • Causes bacteremia, endocarditis, osteomyelitis, and septic arthritis, and often, meningitis
    • Can be a primary infection, can be secondary to other infections, like endocarditis, osteomyelitis, and other infections
    • Rapidly progressive, with severe tissue damage due to toxins and enzymes
    • High mortality rate, especially in patients with underlying conditions
    • Forms biofilms on medical devices, leading to persistent infections

Other bacteria

  • Beta-hemolytic streptococci
  • Enterococcus spp.
  • Pseudomonas aeruginosa

Implications of Pathogenicity

  • Clinical Presentation: The virulence mechanisms of a pathogen influence the specific clinical signs and symptoms (e.g., fever, headache, stiff neck, altered mental status, skin rash)
  • Diagnosis: Knowledge of virulence factors guides the selection of appropriate diagnostic tests (e.g., antigen detection tests, molecular methods). Specific features help with diagnosis
  • Treatment: The pathogen’s virulence dictates the selection of appropriate antimicrobial therapy
    • Antimicrobial Resistance
    • Ability to form biofilms
  • Prevention: Knowledge of the transmission routes and virulence factors helps in the development of preventive measures. This includes:
    • Hand hygiene
    • Infection control practices
    • Vaccinations

Key Terms

  • Pathogenicity: The ability of a microorganism to cause disease
  • Virulence: The degree of pathogenicity, i.e., the extent of the disease the pathogen can cause
  • Etiology: The cause of a disease
  • Transmission: The spread of a pathogen from one host to another or from a source to a host
  • Colonization: The establishment of a microorganism on a host surface (skin, mucosa)
  • Invasion: The entry of a pathogen into host tissues
  • Immune Evasion: Mechanisms used by pathogens to avoid or subvert the host’s immune response
  • Toxins: Harmful substances produced by pathogens
  • Adhesins: Surface structures or proteins that facilitate the attachment of pathogens to host cells
  • Capsule: A polysaccharide or protein layer that surrounds some bacteria, protecting them from phagocytosis
  • Endotoxin (LPS): A component of the outer membrane of Gram-negative bacteria that triggers a strong inflammatory response
  • Exotoxins: Toxins secreted by bacteria
  • Biofilm: A community of microorganisms that adhere to a surface and are encased in a matrix of extracellular substances
  • Sepsis: A life-threatening organ dysfunction caused by a dysregulated host response to infection
  • Antibiotic Resistance: The ability of bacteria to survive and multiply in the presence of antibiotics
  • Antimicrobial Stewardship: A coordinated program that promotes the appropriate use of antibiotics, improving patient outcomes and reducing antimicrobial resistance
  • CSF: Cerebrospinal fluid
  • Intracellular pathogen: A microorganism that can survive and replicate inside of host cells
  • Blood-brain barrier: A protective barrier that prevents pathogens from entering the central nervous system