Human-Pathogen Interactions

Definitions and Concepts

Understanding the interaction between microbes and human hosts is fundamental to microbiology and infectious disease. Key terms include:

• Pathogen: A microbe that causes disease in its host.

• Opportunistic pathogen: A microbe that does not normally cause disease but can do so in immunocompromised hosts.

• Infection vs. Disease: Infection is the entry and multiplication of a microbe in the host, while disease occurs when the pathogen causes damage to host tissues.

• Example: HIV infection may not immediately cause disease, but progression leads to AIDS.

Microbial Adherence

Mechanisms of Attachment

Adherence is the enhanced ability of microbes to attach to a cell or surface, a critical first step in infection.

• Pathogens bind to tissues via receptor molecules on the host cell surface.

• Adhesins: Glycoproteins or lipoproteins on the pathogen's surface that enable binding to host cells.

• Adherence Structures: Pili, flagella, capsules, and fimbriae are specialized structures that facilitate attachment.

• Example: Streptococcus pyogenes uses M protein for adherence; Staphylococcus aureus uses SdrG adhesin to bind fibrinogen.

Colonization and Invasion

Establishment and Spread in the Host

After adherence, pathogens must colonize and invade host tissues to establish infection.

• Colonization: Growth of microorganisms after gaining access to host tissues, often starting at mucous membranes (epithelial cells coated in mucus).

• Invasion: The ability of a pathogen to enter host cells/tissues, spread, and cause disease.

• Bacteremia: Presence of bacteria in the bloodstream.

• Septic shock: Bacteria multiply in the bloodstream, causing systemic infection, massive inflammation, and potentially death.

• Example: Streptococcus pyogenes can invade deeper tissues after colonization.

Virulence

Factors and Measurement

Virulence is the relative ability of a pathogen to cause disease, determined by various strategies and factors.

• Virulence factors: Substances or strategies that enable a pathogen to establish infection and cause damage (e.g., toxins, enzymes, adherence structures).

• Measuring Virulence: The LD50 (lethal dose 50) is the amount of an agent that kills 50% of animals in a test group.

• Example: Streptococcus pneumoniae has a lower LD50 (more virulent) than Salmonella enterica.

Attenuation

Loss of Virulence and Vaccine Development

Attenuation refers to the decrease or loss of virulence of a pathogen, often occurring when grown in laboratory culture.

• Mechanism: Pathogens may lose virulence genes that are not advantageous outside the host environment.

• Importance: Attenuated strains are used in vaccine development (e.g., live attenuated vaccines).

Salmonella Virulence Factors

Genetic Elements and Mechanisms

Salmonella species possess numerous virulence factors encoded on pathogenicity islands and plasmids.

• Pathogenicity islands: Clusters of genes on the chromosome that encode virulence traits (e.g., SPI1, SPI2).

• Virulence plasmids: Extrachromosomal DNA carrying additional virulence genes.

• Examples of virulence factors:

  • Type I fimbriae (adherence)

  • Endotoxin in LPS layer

  • Injectisome (protein secretion system)

  • Siderophores (iron acquisition)

  • Cytotoxins (inhibit host cell protein synthesis)

Compromised Host

Susceptibility to Infection

A compromised host has one or more inactive resistance mechanisms, increasing the probability of infection.

• Factors: Age, underlying disease, immunosuppressive therapy, malnutrition, trauma, etc.

• Opportunistic pathogens: Cause disease only when normal host resistance is absent.

Enzymes as Virulence Factors

Tissue-Destroying Enzymes

Pathogens produce enzymes that facilitate invasion and damage host tissues.

• Hyaluronidase: Breaks down hyaluronic acid in connective tissue, aiding spread.

• Collagenase: Degrades collagen, allowing deeper tissue invasion.

• Coagulase: Forms clots to protect pathogens from immune cells.

• Streptokinase: Breaks down clots, releasing pathogens into tissues.

• Example: Staphylococcus aureus produces coagulase; Streptococcus pyogenes produces streptokinase.

Exotoxins

Types and Mechanisms

Exotoxins are proteins released by pathogens that inhibit host cell function or kill host cells. They are classified into three main categories:

• AB toxins: Consist of two subunits (A and B). The B subunit binds to host cell receptors, and the A subunit exerts toxic effects inside the cell.

• Cytolytic toxins: Degrade cytoplasmic membrane integrity, causing cell lysis and death. Hemolysins lyse red blood cells.

• Superantigen toxins: Cause overstimulation of the immune system, leading to toxic shock syndrome (TSS).

Examples:

• Diphtheria toxin (AB toxin): Blocks protein synthesis.

• Cholera toxin (AB toxin): Causes severe diarrhea.

• Botulinum toxin (AB toxin): Causes flaccid paralysis by inhibiting acetylcholine release.

• Tetanus toxin (AB toxin): Causes spastic paralysis by blocking inhibitory neurotransmitter release.

• Staphylococcal α-toxin (cytolytic): Kills nucleated cells and lyses erythrocytes.

• Staphylococcus aureus and Streptococcus pyogenes (superantigens): Cause TSS.

Endotoxins

Characteristics and Detection

Endotoxins are components of the outer membrane of gram-negative bacteria, specifically the lipopolysaccharide (LPS) portion.

• Less toxic than exotoxins, but can cause fever and inflammation.

• Detection: Limulus amoebocyte lysate (LAL) assay is used to detect endotoxin presence.

• Example: Endotoxin release during Salmonella infection can trigger septic shock.

Properties of Exotoxins and Endotoxins

Comparison Table

The following table summarizes the key differences between exotoxins and endotoxins:

Review Questions

• Why do gram-positive bacteria not produce endotoxins? They lack an outer membrane containing LPS.

• What key features are shared by all AB exotoxins? They have a binding (B) subunit and an activating (A) subunit; both are proteins.

• What circumstances can contribute to attenuation of a pathogen? Evolution or loss of virulence genes that are no longer advantageous.

Additional info: These notes cover topics from Ch. 24+25 (Microbial Symbioses with Humans | Microbial Infection and Pathogenesis) and Ch. 28 (Immune Disorders and Antimicrobial Therapy), with relevant context from Ch. 4 (Microbial Growth and Its Control) and Ch. 2 (Microbial Cell Structure and Function).