Bacterial Pathogenicity

5 steps to pathogenicity

1. Gain host access

   • Endogenous → commensals

   • Exogenous

2. Bacterial adhesion

3. Nutrient acquisition

   • Iron acquisition → siderophores

     • E. coli enterobactin

4. Host defence evasion

   • Evade phagocytosis

   • Resist complement and lysozyme

   • Hide from defences

5. Host damage

   • Endotoxins → gram -ves

   • Exotoxins → gram +ves

   • Immune mediated damage

Pathogenicity

ability of infectious agent to cause disease

Virulence

measure of pathogenicity

Pathogenesis

process of disease progression

Nosocomial infection

healtcare-associated infection

Host access endogenous

• Staph pseudintermedius

• Esch-eri-chia coli

• Bordetella bronchiseptica → respiratory tract

• Pasteurella multiocida → oropharynx

Host access exogenous

• From environment → C. tetani

• Another animal → Strep equi (strangles)

Host adhesion

• E. coli:

  • P-fimbriae (uroepithelium) → resists urine flushing

  • K88 (cow, pig GIT)

  • K99 (cow, pig, sheep GIT)

• Bordetella bronchiseptica (kennel cough)

  • Filamentous haemagglutinin → resists mucociliary escalator

• Di-chelo-bacter nod-o-sus (ovine footrot)

  • fimA gene → fimbriae adhering to keratin → source of pathogenicity

  • Creates environment for secondary anaerobic more virulent bacteria

Nutrient acquisition - iron

• Pathogens fail to grow if starved of iron

• Sources of iron

  • Haemoglobin

  • Transferrin

  • Lactoferrin

Evading innate phagocytosis

• Hydrophilic surfaces → phagocytosis defence

  • Capsule

  • LPS (gram -ves)

• Nonstabilising capsule or LPS → complement cannot bind for opsonophagocytosis

  • recap

    • opsonophagocytosis - via C3b opsonisation (alternative pathway)

      • S. aureus capsule polysaccharide

Evading adaptive phagocytosis

(molecular mimicry)

• Antibody mediated opsonophagocytosis

  • complement activation via classical pathway

  • IgG or IgM trigger complement system

• Bacteria avoid provoking antibody production → molecular mimicry (look like self antigens)

  • K1 antigen of E. coli → sialic acid

  • K5 antigen of E. coli → de-sulfo-heparin

  • Beta haemolytic strep → hyaluronic acid capsule

Evading adaptive phagocytosis

(other bacterial components) [4]

1. Staph aureus (only gram +ves) → protein A

   • Protein with Fc gamma binding sites → coats itself with host IgG to avoid detection

2. Leukocidins

   • Beta haemolytic strep

   • Mannheimia haemolytica leukotoxin

3. Antichemotaxins → prevent complement activation

   • IL-8 protease

   • C5a cleavage

4. Strep equi (only gram +ves) → M protein

Hiding from host defences inside cells

• Obligate intracellular pathogens

• Facultative intracellular pathogens

  1. Brucella abortus

  2. Listeria monocytogenes

  3. M. bovis

  4. Staph aureus

  5. Salmonella enterica

3 main mechanisms for surviving and growing inside host cells

1. Inhibit phagolysosome production

2. Lyse phagosome membrane and escape into cytoplasm

3. Resist killing by lysosome (e.g. catalase)

Exotoxins (gram +ves)

• Clostridial toxins (alpha, beta, epsilon, iota)

• Staph haemolysins (alpha, beta)

• Staph leucocidins (beta toxin, panton valentine leucocidin → PVL)

• S. aureus (toxic shock syndrome toxin -1 → TSST-1)

  • increases TNF-a and IL1 levels

• Tetanospasmin (tetanus toxin)

• Botulinum toxin

Endotoxins (gram -ves) → LPS lipid A mechanism

1. LPS released from bacterial cell during cell death

2. Recognised by CD14 macrophage receptor

3. IL-1 and TNF-alpha release → cytokine storm

4. Activate clotting cascade, inducing pyrexia and systemic clinical signs

Systemic response to endotoxins

• Pyrexia

• Complement activation

• Leucopaenia

• Thrombosis, DIC (disseminated intravascular coagulopathy)

4 steps of endotoxic shock

1. Cytokine storm

2. Systemic vasodilation

3. Hypotension

4. Circulatory collapse → death

Immune mediated injury → bacteria

• Mostly Mycobacterium (TB/Johnes)

• Immunopathological tissue destruction → granulomatous response

  • high influx of WBCs

  • body walls off

• Cytokine damage occurs → body fights off infection