FFP1L4 Pathogenesis of bacterial infection 24 JD STUD with PS

NORMAL FLORA (MICROBIOME)

  • Composed of good bugs, commensals, or microbiota.

  • Found in or on our bodies without causing disease.

  • Mostly non-pathogenic, but can lead to infections in certain situations:

    • If they escape their usual locations.

    • When barriers are breached.

    • If the host is immunosuppressed.

VIRULENT BACTERIA

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

  • Primary Pathogens:

    • Can cause diseases due to presence within the host.

    • Can coexist with normal flora without causing disease (termed ‘colonized’).

  • Virulence Factors:

    • Specific genetic, biochemical, or structural features that enhance the pathogen’s ability to cause disease.

OPPORTUNISTIC BACTERIA

  • Low intrinsic virulence; typically don’t cause infections in healthy patients.

  • May lead to serious infections in:

    • Immunocompromised individuals.

    • Presence of foreign bodies.

WHY DOES INFECTION OCCUR?

  1. The organism is virulent.

  2. The size of the inoculum (population).

  3. The portal of entry.

  4. Survival within the host.

  5. The state of the host.

PATHOGEN TRANSMISSION

From the Pathogen’s Perspective

  1. Get in

  2. Attach to cells.

  3. Defeat/evade the immune system.

  4. Cause damage to host cells.

  5. Get out and spread further.

PORTALS OF ENTRY

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

  2. Inhalation: e.g., Tuberculosis through aerosols.

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

  4. Sexual Contact: e.g., Chlamydia.

  5. Vertical Transmission (mother to child): e.g., Group B Streptococcus.

ADHESION

  • Critical for bacteria to bind to host cells

  • Mechanism:

    • Receptor/ligand mediated processes

BIOFILM

  • Adhesion of bacteria on the surfaces of foreign materials in the body (e.g., joint replacements or replaced heart valve).

  • Provides protection to bacteria, making eradication challenging.

INVASION

  • Pathogens employ biochemical virulence factors called Invasins, which:

    • Are proteins that damage host cells.

    • Facilitate pathogen spread and invasion

IMMUNE EVASION

  • Bacteria develop mechanisms to prevent immune clearance, such as:

    • Inhibiting phagocytosis.

    • Surviving within phagocytes.

    • Destroying immune cells.

Inhibition of Phagocytosis

  • Capsule: Polysaccharide layer outside the cell membrane, associated with pathogens causing meningitis and pneumonia

Survival Within Phagocytes

  • Listeria monocytogenes: Escapes phagosome.

  • Mycobacterium tuberculosis: Prevents phagosome/lysosome fusion.

  • Staphylococcus aureus: Survives within the phagolysosome.

Immune Cell Destruction/Evasion

  • Bacteria produce enzymes targeting immune cells, e.g.:

    • Leucocidins

    • Streptolysin

    • Coagulase

DAMAGE TO HOST CELLS

  • Bacterial enzymes not only damage host tissues but also aid in immune evasion through:

    • Invasins

    • Toxins

    • Superantigens.

Types of Toxins

  1. Endotoxins:

  • Integral part of the bacterial cell envelope (LPS - Lipopolysaccharide).

  • Released through cell lysis; can induce septic shock through pro-inflammatory responses.

  1. Exotoxins:

  • Secreted polypeptides primarily from Gram-positive bacteria.

  • Target specific cells for toxic effects.

Superantigens

  • A type of exotoxin that causes hyperactivation of the immune system by non-specifically binding to MHC Class II on T cells, leading to shock syndrome.

EXOTOXINS VS ENDOTOXINS

Features

Endotoxin

Exotoxin

Source

Gram-negative bacteria

Gram-positive >> Gram-negative

Composition

Lipopolysaccharides

Polypeptides/proteins

Mechanism of Release

Released on bacterial lysis

Secreted/released during bacterial activity

Examples

Meningococcal sepsis

Cholera, Tetanus, Botulism

DISSEMINATION – HOW PATHOGENS SPREAD IN THE BODY

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

  2. Spread through bloodstream (haematogenous).

  3. Spread through the lymphatic system.

  4. Spread carried within macrophages (e.g., Typhoid).

  5. Ascending/descending spread within a tract.

HOW ARE PATHOGENS TRANSMITTED?

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

  2. Respiratory transmission (coughing, sneezing).

  3. Gastrointestinal (diarrhoea).

  4. Sexual transmission (genital discharge/ulcer).

  5. Vertical and perinatal transmission (from mother to newborn).

  6. Environmental transmission (contaminated objects - fomites).

HOST RISK FACTORS FOR INFECTION

  • Factors that increase susceptibility to infections include:

    • Extremes of age.

    • Diabetes.

    • Immunosuppression (disease induced: cancer, asplenism, HIV, renal, hepatic failure; medication induced: chemotherapy, steroids).

    • Major breaches in skin/mucosa (recent surgery).

    • Presence of prosthetic materials (e.g., IV lines, urinary catheters).

    • Anatomical abnormalities or malfunctions.

    • Antibiotic therapy leading to Clostridium difficile infections and other complications.