Enterobacteriaceae and Gut Diseases

Enterobacteriaceae and Gut Diseases

1. Enterobacteriaceae

   • Small, Gram -ve rods (2-5 by 0.5 um)
     • Inner membrane - phospholipid bilayer
       • Solid membrane - murein layer, muopeptide, peptidoglycan
         • Outer membrane - lipopolysaccharide, lipoprotein (and O antigen repeat side chains)
           • LPS is involved in shock, fever, hypoglycaemia, DIC, thrombosis, vascular permeability, hypotension and decreased iron levels
   • Mostly motile with peritrichious flagella (except Shigella and Klebsiella)
   • Oxidase negative facultative anaerobes
   • Reduce nitrate and ferment glucose (and other carbohydrates)
   • Some strains are opportunistic pathogens, some are true pathogens (Salmonella, Yersinia, some E. coli, Shigella)
   • Many genera: Escherichia, Salmonella, Shigella, Yersinia, Klebsiella, Proteus, Enterobacter etc.
   • Sites of infection
     • CNS - Escherichia
     • Bloodstream - Escherichia, Enterobacter, Klebsiella
     • Lower respiratory tract - Klebsiella, Enterobacter, Eshcerichia
     • Gastrointestinal - Salmonella, Escherichia, Shigella, Yersinia
     • Urinary tract - Proteus, Escherichia, Klebsiella, Providencia
   • Different genera have different antigens on their capsule
     • E. coli - K antigen, S. typhi - Vi antigen, K. pneumonia - serotype antigen

2. Exotoxins vs Endotoxins

   • Exotoxins
     • Released from the cell before or after lysis
     • Are proteins
     • Heat-labile
     • Antigenic and immunogenic
     • Toxoids can be produced
     • Specific effect on host
     • Profuced by Gram -ve and +ve bacteria
   • Endotoxins
     • Integral part of cell wall
     • Are LPS - lipid A is the toxic component (hydrophobic fatty acids)
     • Heat-stable
     • Antigenic
     • Toxoids cannot be produced
     • Many effects on host
     • Produced by Gram -ve organisms only

3. Bacillary Dysentry (Shigellosis)

   • Acute infectious disease of the intestines caused by dysentery bacilli
   • Symptoms
     • Fever
     • Abdominal pain
     • Diarrhoea
     • Tensmus (constant feeling of needing to defacate)
     • Stool mixed with mucus, blood and pus
     • Shock and toxic encepalopothy
   • Etiology
     • Gram -ve, short rod, non-motile
     • Shigella
     • 4 groups, 47 serotypes
       • S. dysenteriae is the most severe
       • S. flexneri causes epidemics and can become chronic
       • S. boydii found in tropical areas
       • S. sonnei is the most mild
   • Pathogenicity
     • Endotoxins and interotoxins (exotoxins)
     • Invasiveness
       • Attach-penetrate-multiply
     • Resistance - strong
       • Can survive 1-2 weeks on fruit/vegetables/soil
         • Destroyed by heating for 30 mins at 60 'C
   • Transmitted via faecal-oral route
   • Immunity is short and unsteady - no cross-immunity
   • Treated with Quinolones
   • Features
     • Diffuse fibrous exudative inflammation and lesions in sigmoid and rectum with superficial ulceration
     • Hyperemia, oedema, leukocyte infiltration and necrosis

4. Shigella Infection

   • Bacteria enters intestine
     • Normal bacterial flora and sIgA prevent attachment
     • Bacteria penetrate mucus and multiply in epithelial cells and propria lamina
       • Inflammation and vessel contraction
         • Superficial mucosal necrosis and ulcer
           • Diarrhoea mixed with blood, pus and mucus with abdominal pain
       • Endotoxin
         • Endogenous pyrogen
           • Fever
         • Allergy to endotoxin
           • Increased dimethyl-adrenaline
             • Micro-circulatory failure
               • Shock, Disseminated Intravascular Coagulation (DIC)
               • Cerebral oedema/hernia
       • Invade neighbouring cells to form abcess and evade immune system - rarely enter blood stream

5. Typhoid Fever vs Salmonellosis

   • Salmonella
     • Caused by Salmonella enterica
     • Treatment involves oral rehydration
     • Causes nausea and diarrhoea
     • Infection
       • Bacteria enters intestinal epithelial cell
         • Multiplies within vesicle of cell
           • Multiplication in mucosal cells results in inflammatory response
             • Diarrhoea
           • Bacteria can cross epithelial membrane to enter lymphatics and blood stream
   • Typhoid fever
     • Caused by Salmonella typhi
     • Bacteria spread throughout body in phagocytes
     • 1-3% of patients become chronic carriers
     • Treated with Quinolones and Cephalosporins
     • Causes high fever and high mortality
   • Both involve infection and endotoxins
   • Both diagnosed by isolation and serotyping

6. Vibrios

   • Cholera
     • Vibrio cholera serotypes that produce cholera toxin (O:1 and O:139)
       • Toxins cause cells to release Cl-, HCO- and water
       • Exotoxins
     • Causes diarrhoea and severe water loss
     • Treated with doxycycline and rehydration
   • Non-cholera Vibrios
     • Usually come from contaminated crustaceans or mollusks
     • Include V. cholera subtypes (not including O:1 or O:139), V. parahaemolyticus and V. vulnificus
     • Causes cholera-like diarrhoea but milder (V. parahaemolyticus) and rapidly spreading tissue destruction (V. vulnificus)
     • Caused by infection, enterotoxin (V. parahaemolyticus)/siderophores (V. vulnificus)
     • Treated with antibiotics (and rehydration for V. parahaemolyticus)

7. Campylobacter

   • Campylobacter jejuni
   • Causes fever, abdominal pain and diarrhoea
     • Caused by infection
   • Found in chicken and cows' milk

8. Helicobacter

   • Helicobacter pylori
   • Ammonia from bacterial activity neutralises stomach HCl
     • Causes more HCl production
       • Leads to peptic ulcers
   • Diagnosis by urea test and and bacterial culture
   • Caused by infection
   • Treatment with antibacterials

9. Yersinia

   • Y. enterolytica/ Y. pseudotuberculosis
   • Symptoms
     • Diarrhoea
     • Abdominal pain (usually mild)
       • May be confused with appendicitis
   • Caused by infection and endotoxins
   • Found in meat and milk
   • Diagnosed with bacterial culture and serotyping

10. Clostridium vs Bascillus

    • B. cereus
      • Causes nausea, vomiting and diarrhoea
      • Caused by intoxication
      • Diagnosed by bacterial isolation
      • Found in reheated rice
    • C. difficile/C. perfringens
      • Caused by infection and exotoxin
      • Cause diarrhoea (to colitis for C. difficile)
      • Diagnosed by bacterial isolation/cytotoxin assay (for C. difficile)
      • C. perfringens found in meat
      • C. difficile caused by elimination of normal flora
      • C. difficile treated with metronidazole

11. Escherichia coli

    • Bacteria attach to intestinal cells via fimbrae
    • Produces toxins
    • Cells may aggregate
    • Entertoxigenic, Enteroinvasive, Enteraggregative
      • Cause Traveller's Diarrhoea
    • Shiga-toxin producing (STEC)
      • Causes Shigella'like dysentery, hemorrhagic colitis and haemolyitic uremic syndrom
    • Detected by bacterial isolation
    • STEC treated with Quinolones and Cephalosporins (other treated with rehydration)