Path 7 Pathogenesis of Bacterial Infection

Course Details

  • Class: Year 1

  • Course: Undergraduate Medicine

  • Lecturer: Dr. Ellen Browne

  • Date: 21st October 2025

  • Institution: RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

  • Session ID: FFP1ML4

Learning Outcomes

  1. Differentiate the normal flora (microbiome) from virulent & opportunistic pathogens.

  2. Explain how pathogens are transmitted.

  3. Describe how pathogens gain entry into the body and cells.

  4. Explain how pathogens avoid being killed by the immune system.

  5. Describe how pathogens spread in the body.

  6. Differentiate between endotoxins and exotoxins.

  7. Discuss host risk factors for infection.

Pathogenesis

  • Definition: The mechanisms involved in the production of disease.

Key Question

  • How can something so small cause so much trouble?

Definitions

  • Pathogen: A microorganism that is able to cause disease (pathology).

  • Pathogenicity: The ability to produce disease in a host.

  • Virulence: The capacity/severity of a microorganism to cause disease or to invade.

Pathogenicity vs. Virulence

  • Pathogenicity: Refers to the capability of an organism to cause disease.

  • Virulence: Refers to the degree of pathogenicity; it indicates how severe the disease can be once an infection occurs.

Normal Flora (Microbiome)

  • Described as good bugs, commensals, or microbiota.

  • Present in or on our bodies without causing disease.

  • Mostly non-pathogenic.

  • Can lead to infection if:

    • Escape from their usual location.

    • The barrier is breached.

    • The host is immunosuppressed.

Virulent Bacteria

  • Definition: Bacteria with an increased ability to invade or damage the host.

  • Primary pathogens: Able to cause disease due to their presence within the host (can live among normal flora without causing disease, termed as being “colonized”).

  • Virulence factors: Genetic, biochemical, or structural features of a pathogen that enhance its ability to produce disease.

Opportunistic Bacteria

  • Definition: Bacteria with low intrinsic virulence that usually don’t cause infections in immunocompetent patients.

  • Can cause serious infections under certain circumstances, e.g., immunocompromised host or presence of foreign bodies.

Why Does Infection Occur?

  1. The organism is virulent.

  2. The size of the inoculum.

  3. The portal of entry.

  4. Survival in the host.

  5. The state of the host.

Transmission of Pathogens

  • From the pathogen’s perspective:

    • Get in – Portal of Entry.

    • Attach to cells.

    • Defeat/evade the immune system.

    • Cause damage to host cells.

    • Get out and spread further.

Portals of Entry for Pathogens

  1. Ingestion: E.g., Salmonella food poisoning.

  2. Inhalation of droplets or aerosols: E.g., Tuberculosis.

  3. Penetration/Inoculation: E.g., Staphylococcus aureus.

  4. Sexual: E.g., Chlamydia.

  5. Vertical transmission: E.g., Group B Streptococcus.

Adhesion

  • Adhesion of bacteria to host cells is required for establishing stable populations within the host.

  • Prevents bacterial clearance through mechanical host defenses.

  • Occurs via receptor/ligand-mediated processes involving adhesins, which are small bacterial proteins that recognize specific receptors on host cells.

Biofilm

  • Definition: A formation of bacteria adhered to the surface of foreign material (e.g., joint replacements, heart valves).

  • Protects bacteria, complicating eradication efforts without removal of the prosthesis.

Invasion

  • Pathogens may use biochemical virulence factors called invasins to facilitate invasion.

  • Invasins:

    • Proteins that damage host cells and facilitate spread and invasion.

    • Examples: Hyaluronidase, Kinase, Collagenase.

Immune Evasion

  • Bacteria induce immune responses for eradication by host immune systems.

  • To survive, bacteria develop mechanisms to evade immune clearance:

    • Inhibition of phagocytosis: The ingestion of bacteria by phagocyte white blood cells (e.g., neutrophils).

    • Survival within phagocytes.

    • Destruction of immune cells.

Inhibition of Phagocytosis

  • Mechanism: Presence of a capsule composed of polysaccharides which sits outside the cell membrane.

  • Involvement in diseases associated with meningitis and pneumonia (e.g., Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae).

Survival within Phagocytes

  • Mechanisms include:

    • Escape the phagosome: E.g., Listeria monocytogenes.

    • Prevent phagosome/lysosome fusion: E.g., Mycobacterium tuberculosis.

    • Survival within phagolysosome: E.g., Staphylococcus aureus.

Immune Cell Destruction/Evasion

  • Some bacteria produce enzymes targeting immune cells or preventing their function:

    • Leucocidins: Pore-forming enzymes targeting phagocytes (e.g., Panton-Valentin Leucocidin from Staphylococcus aureus).

    • Streptolysin: Pore-forming enzyme from Streptococci.

    • Coagulase: Produced by S. aureus, converts fibrinogen to fibrin promoting clotting that coats the bacteria, acting as a barrier to immune cells.

Damage to Host Cells

  • Bacterial enzymes damage host cells and contribute to immune evasion.

  • Components involved:

    • Invasins: Aid in cellular damage.

    • Toxins: Poisons damaging host tissues.

    • Superantigens: Substances that cause excessive immune activation.

Bacterial Toxins

  • Two Types:

    1. Endotoxins

    2. Exotoxins

Endotoxins

  • Integral part of the bacterial cell envelope.

  • Released upon cell lysis or turnover.

  • Example: LPS (Lipopolysaccharide) - characteristic of Gram-negative bacteria.

  • Can induce a pro-inflammatory cascade leading to septic shock.

Exotoxins

  • Polypeptide molecules produced primarily by living Gram-positive bacteria.

  • Released during cell lysis, bacterial replication, or by specific antibiotics (e.g., β-lactam antibiotics).

  • Can target specific cells inducing local or distal toxic effects.

    • Types of exotoxins include:

    • Cytotoxins

    • Neurotoxins

    • Enterotoxins

Superantigens

  • A type of exotoxin.

  • First identified in strains of Staphylococcus aureus (e.g., TSST-1).

  • Causes hyperactivation of the immune system mediated by interaction with MHC Class II on T cells.

  • Non-specific binding leads to a polyclonal expansion of T cells resulting in shock syndrome.

Comparison Between Exotoxins and Endotoxins

Features

Endotoxin

Exotoxin

Source

Gram-negative bacteria

Gram-positive > Gram-negative bacteria

Chemical Composition

Lipopolysaccharides or lipooligosaccharides

Polypeptides or proteins

Mechanism of Release

Released on bacterial cell lysis

Secreted by bacteria, or released on cell lysis

Examples

Meningococcal sepsis

Cholera, Tetanus, Botulism

Dissemination – How Pathogens Spread in the Body

  1. Spread through tissues or tissue planes (contiguous).

  2. Spread through the bloodstream (haematogenous).

  3. Spread through the lymphatic system.

  4. Carriage within macrophages (e.g., Typhoid).

  5. Ascending/descending spread within a part of the body.

How Are Pathogens Transmitted?

  1. Person-to-person via direct contact (skin carriage).

  2. Respiratory transmission: Through coughing or sneezing.

  3. Gastrointestinal transmission: Through diarrhoea.

  4. Sexual transmission: Through genital discharge or ulcers.

  5. Vertical & Perinatal: From mother to newborn.

  6. Environmental transmission: From contaminated inanimate objects (fomites).

Host Risk Factors for Infection

  • Certain factors may increase susceptibility to infection and worsen disease manifestations.

Key Host Factors

  • Extremes of Age: Very young or old individuals are typically more susceptible.

  • Underlying Health Issues:

    • Diabetes

    • Immunosuppression: Includes disease induced by cancer, asplenism, HIV, renal, and hepatic failure.

    • Medications: Use of chemotherapy, steroids, or other immunosuppressive medications.

  • Major Breaches in Skin/Mucosa: Recent major surgeries that create a portal of entry.

  • Prosthetic Materials: Such as IV lines, urinary catheters, and prosthetic joints or heart valves, leading to biofilm formation.

  • Anatomical Abnormalities: Post-surgery complications leading to increased infection risks.

  • Antibiotic Therapy: Can cause secondary infections, e.g., Clostridioides difficile after antibiotic use.

Summary

  • Bacteria can be components of normal flora (microbiome) and can opportunistically infect cases of host compromise or exhibit increased virulence.

  • Virulent bacteria can colonize hosts and cause disease, termed primary pathogens.

  • Bacteria can utilize various portals of entry and transmission mechanisms as part of their pathogenesis cycle.

  • Adhesins and invasins facilitate bacterial attachment and entry into the host.

  • Immune evasion mechanisms include inhibition of phagocytosis, survival within immune cells, and destruction of immune cells.

  • Exotoxins and endotoxins cause host cell toxicity through direct damage or regulatory dysregulation.

  • Several risk factors can increase an individual’s susceptibility to infection.