Normal Microbiota and Pathogenicity

Normal Microbiota and Pathogenicity

Normal Microbiota and Pathogenicity

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Normal Microbiota - Our Tiny Tenants

  • Definition: Resident microbes (commensals) on/in healthy individuals; vital for health.
  • Key Sites & Predominant Flora:
    • Skin: Staphylococcus epidermidis, Propionibacterium acnes.
    • Nasopharynx: S. aureus (carrier), Viridans streptococci.
    • Mouth: S. mutans (dental caries), anaerobes (Bacteroides).
    • Colon: Highest load ($10^{11}-10^{12}$/g); >95% anaerobes (Bacteroides fragilis, Clostridium); E. coli.
    • Vagina: Lactobacillus spp. (maintains acidic pH, protective).
  • Beneficial Roles:
    • Vitamin K & B synthesis.
    • Colonization resistance (vs pathogens).
    • Aids immune development.
  • Sterile Sites (Normally): Blood, CSF, Lungs (LRT), Bladder, internal organs.
  • Dysbiosis & Pathogenicity:
    • Dysbiosis: Imbalance in flora; can cause disease.
    • Opportunistic infections: Flora pathogenic if host immunocompromised or flora displaced.

Bacteroides fragilis: most common colon anaerobe; causes intra-abdominal infections if displaced. Normal Human Microbiota Locations and Key Species

Pathogenicity & Virulence - Villains' Toolkit

  • Pathogenicity: Ability to cause disease.

  • Virulence: Degree of pathogenicity. $LD_{50}$ (Lethal Dose): ↓ = ↑ virulence.

  • Infectivity: Ability to colonize. $ID_{50}$ (Infectious Dose): ↓ = ↑ infectivity.

  • Virulence Factors (Arsenal):

    • Adhesion: Critical for colonization.
      • Pili, adhesins (M protein - S. pyogenes, Opa protein).
    • Invasion & Spread: Aid tissue penetration.
      • Enzymes: Hyaluronidase, collagenase, coagulase, kinases, DNase.
    • Evasion of Host Defenses:
      • Capsules (S. pneumoniae): Antiphagocytic, mask PAMPs.
      • Biofilms: Resist antibiotics/phagocytosis.
      • Antigenic variation (Influenza).
      • IgA proteases.
    • Toxins:
      • Exotoxins: Secreted proteins (G+/G-). Potent, specific. Mostly heat-labile. Toxoids (vaccines). Plasmid/phage coded.
        • Types: A-B (Diphtheria, Cholera), membrane-disrupting (lecithinase), superantigens (TSST-1).
      • Endotoxins: Lipid A (LPS of G-). Released on lysis. Fever, DIC, shock (TNF-α, IL-1). Heat-stable. No toxoids.

      ⭐ Lipid A of LPS is the endotoxin component of Gram-negative bacteria, responsible for septic shock.

Host-Pathogen Tango - Infection Unfolded

Dynamic interplay: invading microbes vs. host defenses, shaping infection's course and outcome.

  • Infection Unfolds:
    • Entry: Via portals (e.g., respiratory, GI). Adherence via adhesins.
    • Invasion & Spread: Localized or systemic dissemination.
    • Multiplication: Colonization, often evading host immunity (e.g., capsules, biofilms).
    • Damage: Caused by pathogen (toxins, enzymes) or host response (immunopathology).
  • Critical Factors:
    • Pathogen: Virulence factors, inoculum size (ID₅₀).
    • Host: Immune status, genetic susceptibility, age.
  • Possible Outcomes:
    • Resolution, asymptomatic carrier, latency, chronic disease, or death.

⭐ Infectious Dose 50 (ID₅₀) is the number of organisms needed to infect 50% of exposed individuals. A lower ID₅₀ indicates greater virulence.

Pathogen-host interaction steps diagram

Opportunistic Infections - Friends Turned Foes

  • Commensals or low-virulence microbes causing disease when host defenses are weakened.
  • Key predisposing factors:
    • Immunodeficiency (e.g., HIV, chemotherapy, steroids).
    • Disruption of normal flora (e.g., broad-spectrum antibiotics → C. difficile).
    • Breached anatomical barriers (e.g., trauma, surgery, catheters, burns).
  • Common examples:
    • Candida albicans (oral thrush, vulvovaginitis).
    • Staphylococcus epidermidis (catheter-related infections, endocarditis).
    • Pseudomonas aeruginosa (burn wounds, ventilator-associated pneumonia).
    • Pneumocystis jirovecii (PCP pneumonia in AIDS patients).

Pseudomonas aeruginosa is notorious for causing infections in burn patients and individuals with cystic fibrosis. Pseudomonas aeruginosa infections

  • 📌 Remember SPACE organisms for nosocomial infections (often opportunistic): Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter.

High‑Yield Points - ⚡ Biggest Takeaways

  • Normal microbiota offers colonization resistance, preventing pathogen invasion.
  • Opportunistic pathogens primarily infect immunocompromised individuals or disrupted microbiota sites.
  • Pathogenicity is the capacity to cause disease; virulence quantifies this capacity.
  • Adherence via structures like pili and adhesins is critical for infection initiation.
  • Exotoxins (secreted proteins) and endotoxins (LPS of Gram-negatives) are key virulence factors.
  • Biofilms contribute to chronic infections and increased antimicrobial resistance.
  • Koch's postulates are criteria to link a specific microbe to a specific disease.

Practice Questions: Normal Microbiota and Pathogenicity

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All of the following are true regarding bacterial toxins EXCEPT:

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Flashcards: Normal Microbiota and Pathogenicity

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3 phases of bacterial growth curve: _____ phase, growth/log phase, stationary phase

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3 phases of bacterial growth curve: _____ phase, growth/log phase, stationary phase

lag

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