Microbial Disease Production Notes

Page 1

Introduction to Microbial Diseases

  • Course: MIC 541 - Microbial Disease Production

  • Instructor: Richard Goering, Ph.D.

  • Email: richardgoering@creighton.edu

  • Theme: Understanding the relationship between germs and diseases.

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All About Antibiotics

  • Organization: Alliance for the Prudent Use of Antibiotics (APUA)

  • Mission: Strengthen global defenses against infectious diseases by ensuring access to effective treatment and promoting appropriate antibiotic use to contain drug resistance.

  • Legacy: Dr. Thomas O’Brien’s contributions to antimicrobial resistance were highlighted, including his involvement with the World Health Organization.

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Step 1: Adherence in Infectious Disease Production

  • Definition: The process by which pathogens attach to host cells.

  • Significance: Essential for overcoming host barriers and initiating infection.

  • Mechanism: Must penetrate body surfaces, often aided by wound entry or viral damage to mucous membranes.

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Mechanisms of Adherence

  • Involves:

    • Microbial surface proteins (adhesins): Help bacteria attach to host cells.

    • Host cell receptors (integrins): Targeting points for adhesive interactions.

  • Importance for viruses: They often require specific proteins to bind effectively to host cells.

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Bacterial Adherence Mechanisms: Pili and Fimbriae

  • Pili (Fimbriae): Hair-like structures on gram-negative bacteria that facilitate adherence.

  • Function: Enhances the ability of pathogens to hold onto host cells.

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Non-Pilin Adhesins

  • Gram-positive bacteria: Use non-pilin adhesins that protrude from the cell wall to enhance adherence.

  • Bacterial Capsules: Aid in adherence and biofilm formation by covering surfaces and facilitating bacterial aggregation.

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Biofilm Production

  • Definition: Microbial communities that adhere to surfaces in a protective matrix.

  • Example: Dental plaque formation with bacteria adhering to teeth.

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Quorum Sensing in Biofilms

  • Concept: Bacteria communicate via signaling compounds to coordinate behavior when a critical population density is reached.

  • Outcome: Triggers gene expression related to biofilm formation.

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Step 2: Multiplication of Infectious Agents

  • Goal: Pathogens must replicate to a critical mass necessary to cause damage.

  • Mechanism: Some pathogens may damage the host without direct invasion through toxin production.

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Immunoglobulin A (IgA) in Mucosal Immunity

  • Role: IgA is the predominant antibody produced in mucosal linings (75% of total immunoglobulin).

  • Function: Essential for trapping microbes in mucus to prevent infections.

    • Subclasses: IgA1 and IgA2, primarily present in secretory forms.

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Step 3: Invasion of Host Cells

  • Purpose: Some pathogens invade cells to exploit host resources or evade immune responses.

  • Mechanisms: Production of invasins that stimulate unintended uptake by host cells.

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Step 4: Resistance to Host Defenses

  • Strategies: Pathogens employ methods to withstand host immune responses, including immunosuppression.

  • Example: Increased tuberculosis incidence post-measles due to immunosuppressive effects on lymphocytes.

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Resistance to Host Complement System

  • Capsule Defense: Pathogens like Neisseria gonorrhoeae use capsules to obscure complement-activating surfaces.

  • Inactivation of Factors: Certain bacteria can disabling complement components to avoid immune activation.

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Step 5: Tissue Damage Production

  • Causes: Damage can result from pathogen activity or from the host immune response, often through toxins.

  • Types of Toxins: Exotoxins (actively secreted) versus endotoxins (cell wall components released upon cell lysis).

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Exotoxins: Characteristics

  • Type: Protein molecules produced by both Gram-positive and Gram-negative bacteria.

  • Function: Disrupt host defenses, acquire nutrients, and spread through tissues, valuable for in-vivo survival.

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Major Actions of Exotoxins

  • Cell Disruption: Enzymatic action can kill or affect host cellular functions.

  • Example: Cholera toxin leads to severe dehydration due to watery diarrhea.

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Endotoxins: Characteristics

  • Nature: Lipopolysaccharides found in the outer membrane of Gram-negative bacteria.

  • Impact: Released during cell lysis, triggering significant immune responses.

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High Concentrations of Endotoxins Response to High LPS
Concentrations

  • Risks: Can lead to endotoxic shock, with symptoms such as hypotension and multi-organ system failure due to overwhelming immune response. Endotoxic shock – may be lethal
     Hypotension
     Clotting factors activated - clots formed
     Causes multi-organ system failure