Bacterial Pathogenesis 2

Bacterial Pathogenesis 2

1. Transmission

   • Ingestion
     • Gastroenteritis
     • Typhoid fever
     • Cholera
     • Hepatitis A & E virus
   • Inhalation
     • Into URT
       • Meningococcal
     • LRT
       • Tuberculosis
       • Bacterial pneumonia
   • Penetration
     • Break in skin
       • Claustridium tetani
       • S.aureus
     • Needle stick
       • Hepatitis B, HIV
     • Insect/ tick bite
       • Lyme disease
       • Plasmodium spp
   • Sexual
     • Chlamydia Gonorrhoea Syphilis
     • Human papilloma virus, Herpes simplex, Hepatitis B ,HIV
   • Transplacental
     • Treponema pallidum
     • Listeria monocytogenes
     • Congenital toxoplasmosis
     • Viruses: rubella, VZV
     • Perinatal period
       • Ophthalmia neonatorum
         • gonorrhoea in maternal genital tract

2. Attach to cells

   • Adhesins
     • attach to host tissue
     • specific epithelium receptors
     • Location
       • Fimbriae
       • cell wall adhesins
       • Capsule
   • Fimbriae/pilli
     • Hair-like appendages
     • Attachment
       • each other
       • Host cells

3. Evade/Defeat immun system

   • Motility
     • Flagella
   • Inhibition of phagocytosis
     • survival within phagocyte
       • resist killing
     • Capsule
       • Fx for attachment
       • eg
         • NIsseria meningitides
         • Streptococcus pneumoniae
         • Haemophilus influenzae type b
     • M protien
       • β-haemolytic streptococci
       • attachment + phagocytosis inhibition
   • extracellular substances prdocution
     • promote invasion
       • Invasins
       • Enzymes
         • cause damage to host,
         • bacterial identification
         • Coagulase
           • Causes blood to coagulate
           • Clots protect bacteria phagocytosis
             • host Self mimicry
           • Staphylococci
         • Kinase
           • Dissolves clots
           • Streptokinase
             • Lyses fibrin clots
             • Used in management of MI
           • Staphylokinase
         • Leukocidins
           • Attacks white blood cells
           • Kills them
           • Releases lysosomes
             • cause tissue damage
         • Haemolysin
           • Lyses red blood cell
           • Steptococci
           • Alpha: incomplete lysis
           • Beta: complete lysis
         • Collagenase
           • Breaks down collagen
         • Urease
           • Helicobacter pylori
             • pathogenesis of peptic ulcer disease

4. Cause damage to Cells

   • Direct damage
   • Toxin
     • Endotoxin
       • secreted after pathogen death
       • cause severe inflammation
       • Cell associated substance
         • Lipid A portion of LPS on gram -ve
       • Causes
         • Fever
         • complement activation
         • platelet count
         • septic shock
           • E.coli (LPS)
           • N.meningitides (LOS)
     • Exotoxin
       • secreted by pathogen
         • mostly gram +ve
         • replicating bacterial cells
         • host cells that are lysed
         • because MOA of certain antibacterials
       • Local and distant effects
         • Local
           • tissue necrosis
             • C. perfringens
               • gas gangrene
         • Distant
           • act at sites far away form the site
             • C. tetani toxin
       • Double Jobbing
         • Act at site
         • role in invasion
       • Toxin disease process
         • occur in absence of causing bacteria
         • Food botulism, staphylococcal food poisoning
       • Types
         • Cytotoxins
           • Kills cells
         • Neurotoxins
           • Interferes with normal nerve functioning
         • Enterotoxins
           • GIT effect
   • Superantigens
     • Non-specific activation of T cells
       • cause activation of multiple T cells
     • polyclonal T cell activation
     • massive cytokine release

5. Dissemination/spread

   • Dissemination
     • Spread through tissues or tissue planes
     • Haematogenous
     • Lymphatics
     • Carriage within macrophages
     • Ascending/descending spread within a tract
   • Spread (host to host)
     • Respiratory
       • coughing, sneezing
     • GI
       • diarrhoea
     • Sexually
       • genital discharge /ulcer
     • Vertically & Perinatally
     • Person-to-person (direct contact)
       • skin carriage

6. Host Risk factors

   • Inc susceptability of host infection
   • Inc manifestation of severe infxn
   • Age extremes
   • Diabetes
   • Immunosuppression
     • Disease induced
       • HIV
       • cancer
       • Asplenism
       • Renal Failure
       • Hepatic failure
     • Meds
       • Chemo therapy
       • Steroids
       • Other immunosuppresive meds
   • Major breach in skin/mucosa
     • Recent major surgery
   • Prosthetic material
     • IV lines
     • Urinary cathether
     • Ventilation
     • Prosthetic joints
   • Anatomical abnormality or malfunction
     • mucocilliary impariment
   • Antibiotic therapy