10. Clostridial Infections Flashcards

1
Q

What are the characteristics of the Clostridium genus:

A
  • Gram positive rods (bacillus)
  • Obligate anaerobes (killed by oxygen)
  • Form heat resistant endospores
  • Catalase negative
  • Common inhabitants of GI tract (can be part of normal flora)
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2
Q

How are Clostridium cultured?

A
  1. Anaerobic jars:
    - sealed
    - contains palladium (converts any O2 to H20)
    - contains a gas generator to create environment with H2 and CO2
  2. Anaerobic chambers:
    - sealed
    - more expensive
    - allows for experimentation
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3
Q

Why do Clostridium form endospores?

A
  • They form endospores under adverse environmental conditions such as the presence of oxygen
  • A survival mechanism
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4
Q

What are some features of Clostridium endospores?

A
  • Most clostridium have ovoid subterminal spores
  • C. tetani have round terminal spores
  • C. difficle spores have an exosporium (hair like structures on the surface of the spores help them adhere to each other and host tissue)
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5
Q

What is the importance of Clostridia in agriculture?

A
  • Important for soil maintenance via nitrogen fixin and decomposition of organic matter
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6
Q

What is the importance of Clostridia in industry?

A
  • Can be used to ferment sugars and produce industrially important chemicals
  • Generally chemical synthesis has replaced this role
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7
Q

What are the pathogenic Clostridia and the diseases they cause?

A

Neurotoxic:

  • C. tetani: tetanus
  • C. botulinum: botulism

Enterotoxic:

  • C. perfingins: food poisoning, enteritis necroticans (lethal food poisoning)
  • C. difficile: pseudomembranous colitis

Histotoxic:

  • C. perfingins: gas gangrene
  • C. septicum: atraumatic gas gangrene
  • C. sordelli: necrotic infections
  • Common feature: produce potent protein toxins
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8
Q

What is C. tetani and its mechanism of pathogenesis?

A

C. tetani:

  • produces neutrotoxin = tetanus toxin
  • spore enters deep into wound and germinates in anaerobic environment
  • toxin is released when bacteria die (exotoxin)
  • results in uncontrolled stimulation so muscles by inhibiting neurotransmitter release in relaxation pathway (rigid paralysis)
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9
Q

What is C. botulinum and its mechanism of pathogenesis?

A

C. botulinum:
- causative agent of botulism
- food borne disease (commonly from canned goods)
Pathogenesis:
- spores germinte in food and toxin is produced during vegetative growth
- toxin is ingested
- toxin blocks release of neurotransmitters in contraction pathway resulting in flaccid paralysis

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10
Q

Describe enterotoxic C. perfingins:

A

C. perfingins:

  • aerotolerant anaerobe that forms spores
  • can cause food poisoning
  • produces an enterotoxin
  • causes watery diarrhoea, nausea and abdominal cramps
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11
Q

Describe histotoxic C. perfingins:

A

C. perfingins:

  • Cause gas gangrene
  • Caused by spores germinating in anaerobic tissue
  • Produces an a-toxin: phospholipase that disupts host-cell plasma membranes and causes extensive destruction of cells and tissues
  • Symptoms: muscle necrosis, blackening of skin, gas production in tissue
  • Treatment: usually involves amputation
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12
Q

Who is C. perfingins tested for biochemically?

A
  • Tested for using a Nagler test which detects phospholipase (C. perfingins a- toxin) activity
  • The bacteria is cultured on a media containing human serum or egg yolk
  • If C. perfingins is the bacteria the colonies will be surrounded by zones of tubidity- this is specifically inhibited if antiserum containing a-toxin is present on medium
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13
Q
  • Where are Toxin genes located in C. perfingins?
A
  • a-toxin and perfingolysin O genes are chromosomal (all strains have a- toxin and thus can cause gas gangrene)
  • B-toxin, E-toxin and i-toxin geens are located on large plasmids
  • Enterotoxin is found chromosomally in food poisoning isolates but in plasmids in other isolates
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14
Q

What diseases do C. perfingins cause in animals?

A
  • A variety of enterotoxaemic diseases largely attributed to production of exotoxins
  • 5 types of C. perfingins animal infections:
    Type A: has only a-toxin, causes lamb enterotoxaemia, myconecrosis, avian necrotic enteritis
    Type B: has a toxin, B-toxin and E-toxin, causes necrotic enteritis in sheep
    Type C: has a-toxin and B-toxin. Causes enterotoxamias in most species of animals (due to action of B-toxin)
    Type D: has a-toxin and E-toxin. Pro-e-toxin is produced in gut which activated by trypsin and is absorbed into blood causing enterotoxaemia
    Type E: has a-toxin and i-toxin. Mostly seen in rabbits.
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15
Q

How does the normal microbiota provide non-specific immunity against pathogens?

A
  • Keep potentially harmful opportunistic pathogens in check and inhibit the colonisation by pathogens by:
    1. Producing metabolic products- inhibit growth of many pathogens
    2. Adhering to target host cells
    3. Depleting nutrients essential for growth of pathogens
    4. Stimulating the immune system
  • Issue: antibiotics are not specific to one bacteria they will kill targeted bacteria as well as some of the normal bacteria
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16
Q

What is Enterotoxic Clostridia C. difficile?

A
  • C. difficile is an enterotoxic only opportunistic pathogen
  • It is an opportunistic pathogen that only colonises the gut if normal microbiota is disrupted (usually following broad spectrum antibiotics use)
  • It is the leading cause of diarrhoea in hospitals world wide
  • Strict anaerobe and spore former
17
Q

What is the C. difficile infectious cycle?

A
  1. Reduction of normal gut flora
  2. Ingestion of spores
  3. Spores survive and pass through stomach
  4. Bile salts in small intestine trigger germination events
  5. Anaerobic environment of the colon supports vegetative growth and toxin production
  6. Toxins cause disease
  7. Spore shedding
18
Q

What is C. difficile pseduomembranous colitis?

A
  • Gross section of the lumen of the colon showing colitis: yellowish plaques of fibrin and infammatory cells that overlay normal intestinal mucosa
  • A result of toxins
19
Q

What type of toxins do C. difficile produce?

A
  • They produce A and B toxins
  • These toxins are monoglucosyltransfereases that glucosylate Rho GTPases
  • Cause cell deth from protein inactivation and the breakdown of the actin filament network
  • The action of this toxin results in severe damage to intestinal epithelium
20
Q

What are current C. difficile treatments?

A
  • Discontinuation of antibiotic and fluid replacment
  • More antibiotics:
  • Oral metrindazole and/or vancomycin
  • Relapses are common (due to persistance of spores)
21
Q

What new C. difficile treatments are under consideration?

A

Non-antibiotic treatments such as:

  • Probiotics
  • Intravenous IgG antibodies
  • Monoclonal antibodies
  • Polyclonal antibodies
  • Faecal transplant therapy
22
Q

What impact do C. difficile infections have in animals?

A
  • Pathology varies between animals
  • Under recognised cause of disease in animals
  • Commonly diagnosed cause of enteritis in pigs in USA
  • Risk to humans: exposure to pigs colonised/infected with C. difficile, expsoure to waste/compost made with contaminated pig manure and expsoure through handling or consumption of contaminated meat