Gram Positive: Bacillus & Clostridium (spore-forming rods)

Question 1

General features of Bacillus and Clostridium.

Answer 1

• Gram positive, spore-forming rods
• these cause disease via very potent exotoxins
• Bacillus is aerobic; Clostridium is anaerobic

Question 2

What are the two main pathogenic species of Bacillus? What does each cause?

Answer 2

• Bacillus anthracis: anthrax

- Bacillus cereus: food poisoning

Question 3

Bacillus anthracis and its virulence factors.

Answer 3

• a facultative anaerobe (B. cereus is an obligate aerobe)
• causes anthrax
• the only bacteria with a capsule made from protein! the capsule is coded in the pXO2 plasmid and protects against phagosome-lysosome fusion
• exotoxins: edema factor (EF), protective antigen (PA), and lethal factor (LF); coded in the pXO1 plasmid

Question 4

Explain the pathogenesis of Bacillus anthracis induced anthrax. How does the organism gain entry into the host?

Answer 4

• B. anthracis spores lie dormant in infected soil and animal products (hides, wool, etc.) until they enter the host
• they get phagocytosed and germinate within the macrophage; reproduce in lymphatic system and then invade the bloodstream
• enters the host via skin abrasions (cutaneous anthrax, most common), inspiration (pulmonary anthrax), and ingestion (GI anthrax)

Question 5

Bacillus cereus and its virulence factors.

Answer 5

• an obligate aerobe (B. anthracis is a facultative anaerobe)
• causes food poisoning (spores germinate and secrete exotoxins in food)
• motile, non-encapsulated, and penicillin resistant
• heat-labile toxin causes nausea, abdominal pain, and diarrhea for 12-24 hours
• heat-stable toxin causes severe nausea and vomiting with limited diarrhea
• note that food poisoning is due to ingested toxins, NOT infection; antibiotics will therefore NOT help

Question 6

What are the four major pathogenic strains of Clostridium? What does each cause?

Answer 6

• C. botulinum: botulism
• C. tetani: tetanus
• C. perfringens: gas gangrene
• C. dificile: pseudomembranous enterocolitis
• all are obligate anaerobes
• all can cause death if not treated early

Question 7

What is botulism? What is the pathogenesis? How do patients present? How do we treat it?

Answer 7

• condition characterized by flaccid paralysis
• caused by the ingestion of very lethal neurotoxins by Clostridium botulinum that block ACh release at motor end plates and autonomic terminals; spores germinate and release the exotoxin in foods sealed in an anerobic environment (smoked fish and canned vegetables especially)
• adults present afebrile with bilateral CN palsies (mainly diplopia and dysphagia), which progress to general muscle weakness and then rapidly to respiratory paralysis and death
• infants present with constipation and as “floppy babies”
• treat with an antitoxin (because it’s the exotoxin, not the bacteria, that’s causing the disease)

Question 8

What is tetanus? What is the pathogenesis? How do patients present? How do we treat it?

Answer 8

• condition characterized by tetany (sustained skeletal muscle contraction); contractile paralysis
• classically caused by a puncture wound with a rusty nail contaminated with Clostridium tetani; the bug releases the exotoxin tetanospasmin, which is taken up at the NMJ, enters the CNS, and inhibits the release of GABA and glycine (inhibiting these inhibitory NTs results in tetany)
• patients present with severe muscle spasms, especially lockjaw (trismus) and grotesque grinning (risus sardonicus), which eventually progress to respiratory failure
• neutralize the tetanospamin toxin with Ab, give immunization booster, clean the wound, and give penicillin

Question 9

What is gas gangrene?

Answer 9

• gas gangrene is caused by infection of deep wounds with Clostridium perfringens (necrotic tissue is anaerobic!)
• C. perfringens produces gas in the wound resulting in crepitus in skin infections and gas pockets in muscle

Question 10

What is pseudomembranous enterocolitis? What is it associated with and how do we treat it?

Answer 10

• antibiotic-associated diarrhea
• antibiotics allow Clostridium dificile to superinfect the colon
• C. dif releases 2 exotoxins (A causes diarrhea and B is cytotoxic to colon cells)
• results in enterocolitis characterized by pseudomembranes (red inflamed mucosa with areas of white exudate)
• treat by stopping the initial antibiotic and then giving metronidazole or vancomycin

Question 11

Compare metronidazole and vancomycin in treating pseudomembranous enteroclitis.

Answer 11

• metronidazole is well absorbed by the gut via the lumen or the bloodstream and can therefore be given either orally or via IV
• vancomycin is not absorbed by the gut via the bloodstream and can therefore only be given orally if it is to reach the gut