Microbial Pathogenicity and Virulence Factors: Mechanisms of Infection

Key Concepts in Microbial Pathogenicity

• Pathogenicity: The ability of a microorganism to cause disease.
• Virulence: The extent or degree of pathogenicity.
• Normal Microbiota: Resident microbes, often referred to as commensals.
• Infection: The invasion of normally sterile tissues by microorganisms.
• Pathogen: An infectious agent capable of causing disease.
• Infectious Disease: A disease caused by infection by a pathogen.
• Colonization: The process of establishing a population of organisms in a host.
• Resident Colonizer: An organism that establishes a long-term presence in the host.
• Transient Presence: A short-term presence of an organism in the host.

Major Factors in the Development of an Infection

1. Adherence: Initial Attachment to Host Cells

   Adherence is crucial for colonization and infection.

   Examples of Adhesins and Ligands

   Adhesins on the pathogen surface bind specifically to receptors on host cells.

   • Glycoproteins or Lipoproteins:
     • Viral spikes.
     • May be located on pili (e.g., E. coli, Neisseria gonorrhoeae).
   • Glycocalyx: Found in organisms like Streptococcus mutans.
     • Used to form biofilms.
     • Also involved in the evasion of phagocytosis.
   • Fimbriae: Common in bacteria such as Escherichia coli.
   • M Protein: A key virulence factor in Streptococcus pyogenes.

   Host Surface Receptors

   Adherence requires complementary host surface receptors:

   • Determines which specific tissues are colonized by the pathogen (tissue tropism).
   • Receptors are typically composed of sugars.

2. How Pathogens Penetrate Host Defenses

   Capsules: Preventing Phagocytosis

   • Capsules prevent host phagocytosis.
   • Organisms whose virulence is dependent upon capsules include:
     • Streptococcus pneumoniae
     • Klebsiella pneumoniae

   Cell Wall Components

   • M Protein: Resists phagocytosis and aids attachment.
     • Example: Streptococcus pyogenes
   • Mycolic Acid (Waxy Lipid): Resists digestion within phagocytes.
     • Example: Mycobacterium tuberculosis

   Enzymes and Toxins: Increasing Virulence

   • Exoenzymes: Enzymes secreted by the pathogen that generally increase virulence.
   • Exotoxins: Secreted substances (often exoenzymes) that are poisonous to host tissues, causing cell death.

   Specific Virulence Enzymes

   • Coagulase: Coagulates fibrinogen, leading to blood clot formation.
     • This action isolates the pathogen, protecting it from host defenses.
   • Kinases: Digest fibrin clots, increasing pathogen spread.
     • Streptokinase: Produced by Streptococcus pyogenes (also used therapeutically to treat coronary artery blood clots—biotechnology success!).
     • Staphylokinase: Produced by Staphylococcus aureus.
   • Hyaluronidase: Hydrolyzes hyaluronic acid, dissolving the connective tissue matrix.
     • Increases pathogen penetration and spread.
     • Found in Streptococci and Clostridium difficile.
   • Collagenase: Hydrolyzes collagen, a key connective tissue protein.
     • Associated with the spread of gas gangrene (e.g., Clostridium species).
   • IgA Proteases: Enzymes that specifically destroy IgA antibodies.
   • Leukocidins: Toxins that destroy neutrophils and macrophages (phagocytic cells).
     • Produced by Streptococci and Staphylococci.
   • Hemolysins: Cause the lysis of red blood cells (erythrocytes).
     • This mechanism allows the pathogen to obtain iron from hemoglobin.
     • Examples: Streptococci, Staphylococci, Clostridium perfringens (a cause of gas gangrene).