Skip to main content

Microbiology

Organism Pathogenicity

Understanding the pathogenicity of microorganisms is fundamental to clinical microbiology, enabling effective diagnosis, treatment, and prevention of infectious diseases. Pathogenicity encompasses the ability of a microorganism to cause disease, which is determined by its ability to:

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

This understanding is crucial in the context of blood and bone marrow infections

Organism Pathogenicity in Blood and Bone Marrow Infections

Staphylococcus aureus

  • Etiology: Gram-positive cocci, 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
      • 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, septic arthritis, and other invasive 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

Coagulase-Negative Staphylococci (CoNS)

  • Etiology: Gram-positive cocci, clusters
  • Transmission: Skin flora. Contamination of medical devices or during invasive procedures
  • Virulence Mechanisms
    • Adherence: Forms biofilms on indwelling medical devices. Produces slime
    • Immune Evasion: Lower virulence compared to S. aureus but can still evade the immune system
    • Toxins: Less potent toxins compared to S. aureus
  • Pathogenicity
    • Causes catheter-related bloodstream infections (CRBSI), especially S. epidermidis
    • Can cause endocarditis, especially in patients with prosthetic valves
    • Can cause bone and joint infections
    • Often associated with healthcare-acquired infections
    • Frequently exhibit antimicrobial resistance (e.g., resistance to beta-lactam antibiotics)

Streptococcus pneumoniae

  • Etiology: Gram-positive diplococci, lancet-shaped
  • Transmission: Respiratory droplets
  • Virulence Mechanisms
    • Capsule: Polysaccharide capsule is the primary virulence factor; protects against phagocytosis
    • Adhesins: Promote attachment to respiratory epithelial cells
    • Pneumolysin: A pore-forming toxin that damages host cells
    • IgA protease: Degrades host antibodies
  • Pathogenicity
    • Causes bacteremia, pneumonia, meningitis, and otitis media
    • Often a severe and rapidly progressive infection
    • Can cause endocarditis

Enterococcus spp.

  • Etiology: Gram-positive cocci, pairs, or short chains
  • Transmission: Fecal-oral route; through contaminated medical devices or healthcare workers
  • Virulence Mechanisms
    • Adherence: Surface proteins (e.g., Ace, Ebp) facilitate adherence to host tissues
    • Biofilm Formation: Can form biofilms on medical devices
    • Cytolysin: A pore-forming toxin that damages host cells
    • Antibiotic Resistance: Frequently develop resistance to multiple antibiotics (e.g., vancomycin-resistant enterococci (VRE))
  • Pathogenicity
    • Causes bacteremia, endocarditis, urinary tract infections (UTIs), and wound infections
    • Can cause healthcare-associated infections
    • Often difficult to treat due to antibiotic resistance

Escherichia coli

  • Etiology: Gram-negative rod
  • Transmission: Fecal-oral route, contaminated food or water, or via medical devices
  • Virulence Mechanisms
    • Adhesins: Fimbriae and other surface structures facilitate attachment to host cells
    • Capsule: Protects against phagocytosis
    • Endotoxin (Lipopolysaccharide or LPS): A potent inflammatory stimulus that triggers sepsis and septic shock
    • Exotoxins: Produce various toxins, including Shiga toxins that cause hemolytic uremic syndrome (HUS)
  • Pathogenicity
    • Causes bacteremia, UTIs, pneumonia, and other infections
    • Can cause severe sepsis and septic shock
    • Can cause bone and joint infections

Klebsiella pneumoniae

  • Etiology: Gram-negative rod
  • Transmission: Healthcare settings, spread through contaminated hands, equipment, or respiratory droplets
  • Virulence Mechanisms
    • Capsule: Thick capsule is a key virulence factor; protects against phagocytosis
    • Adhesins: Facilitate attachment to host cells
    • Endotoxin (Lipopolysaccharide or LPS): Triggers inflammation
    • Siderophores: Produce siderophores (e.g., aerobactin) to acquire iron from the host, which is essential for bacterial survival
  • Pathogenicity
    • Causes bacteremia, pneumonia, UTIs, and wound infections
    • Increasingly resistant to antibiotics, including carbapenems (carbapenem-resistant K. pneumoniae (CRKP))
    • Can cause severe infections, especially in immunocompromised patients

Pseudomonas aeruginosa

  • Etiology: Gram-negative rod
  • Transmission: Environment (water, soil, contaminated surfaces), healthcare settings; spreads via contaminated equipment or hands
  • Virulence Mechanisms
    • Adhesins: Promote attachment to host cells
    • Capsule: Protects against phagocytosis
    • Exotoxins: Produce toxins, including exotoxin A, which inhibits protein synthesis and damages host cells
    • Enzymes: Produce enzymes (e.g., proteases, elastases) that damage host tissues
    • Biofilm Formation: Forms biofilms on medical devices
    • Antibiotic Resistance: Naturally resistant to many antibiotics and readily acquires additional resistance mechanisms
  • Pathogenicity
    • Causes bacteremia, pneumonia, UTIs, wound infections, and other infections
    • Difficult to treat due to antimicrobial resistance
    • Can cause severe infections, especially in immunocompromised patients

Brucella spp.

  • Etiology: Gram-negative coccobacilli
  • Transmission: Contact with infected animals or consumption of contaminated animal products (e.g., unpasteurized milk, cheese)
  • Virulence Mechanisms
    • Intracellular Survival: Survives and replicates within phagocytic cells, avoiding immune clearance
    • Capsule: Protects against phagocytosis
    • LPS: Weak endotoxin, less toxic than LPS from other Gram-negatives
  • Pathogenicity
    • Causes brucellosis, a systemic infection with fever, malaise, and various other symptoms
    • Can involve the bone marrow, causing osteomyelitis
    • Can cause endocarditis
    • Chronic infections can occur

Salmonella spp.

  • Etiology: Gram-negative rod
  • Transmission: Fecal-oral route, contaminated food or water
  • Virulence Mechanisms
    • Adherence: Invades epithelial cells of the gut
    • Invasion: Internalized within host cells
    • Capsule: Some strains have a capsule
    • Endotoxin (LPS): Triggers inflammation
    • Toxins: Produce enterotoxins
  • Pathogenicity
    • Causes gastroenteritis (most common), bacteremia, and typhoid fever
    • Can involve the bone marrow, especially in patients with sickle cell disease
    • Can cause osteomyelitis

Fungal Agents

  • Candida spp.
    • Etiology: Yeast
    • Transmission: Endogenous (part of normal flora), contaminated medical devices
    • Virulence Mechanisms
      • Adherence: Adheres to host cells and medical devices
      • Morphotype Switching: Transition between yeast and hyphal forms, which aids in invasion and dissemination
      • Enzymes: Produce enzymes (e.g., proteases, phospholipases) that damage host tissues
      • Biofilm Formation: Forms biofilms on medical devices
    • Pathogenicity
      • Causes candidemia (bloodstream infection)
      • Can involve the bone marrow, causing disseminated infection
      • Can cause endocarditis
  • Histoplasma capsulatum
    • Etiology: Dimorphic fungus (mold in environment, yeast in host)
    • Transmission: Inhalation of spores
    • Virulence Mechanisms
      • Survival in Macrophages: Survives and replicates within macrophages
      • Morphologic Transformation: Changes from mold to yeast in host tissue
      • Capsule: May have a capsule
      • Production of enzymes
    • Pathogenicity
      • Causes histoplasmosis
      • Can disseminate to the bone marrow, causing disseminated infection
  • Coccidioides immitis/posadasii
    • Etiology: Dimorphic fungus
    • Transmission: Inhalation of spores
    • Virulence Mechanisms
      • Spherule Formation: Forms spherules in host tissues, which release endospores
      • Production of enzymes
    • Pathogenicity
      • Causes coccidioidomycosis (Valley fever)
      • Can disseminate to the bone marrow
  • Aspergillus spp.
    • Etiology: Mold
    • Transmission: Inhalation of spores
    • Virulence Mechanisms
      • Adherence: Adheres to host cells
      • Invasion: Invades blood vessels
      • Production of enzymes
    • Pathogenicity
      • Causes aspergillosis (lung infection)
      • Can disseminate to the bone marrow, causing disseminated infection

Implications of Pathogenicity

  • Clinical Presentation: The virulence mechanisms of a pathogen determine the specific clinical signs and symptoms
  • Diagnosis: Knowledge of virulence factors helps select appropriate diagnostic tests. Blood cultures and bone marrow cultures are fundamental
  • Treatment: Understanding the mechanisms of pathogenicity guides antimicrobial therapy. Knowledge of resistance mechanisms dictates the selection of effective antibiotics
  • Prevention: Knowledge of the transmission routes and virulence factors of pathogens allows for the implementation of preventive measures (e.g., hand hygiene, infection control practices, vaccination)

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