Anaerobic infections (clostridium)

Question 1

Characteristics - Clostridium

Answer 1

Anaerobic, spore forming. 4 types, Clost. Difficile, perfringenes, tetani, botulinum. All gram positive rods and all motile except perfringens.

Question 2

Diseases caused - Clostridium

Answer 2

Difficile: antibiotic associated diarrhoea
Perfringens: Food poisoning, gas gangrene, necrotic enteritis
Tetani: tetanus, lockjaw, tetanospasms
Botulinum: botulism (food-borne, wound, infant)

Question 3

Virulence factors - C. Difficile

Answer 3

TcdA and TcdB are clostridial glycosylating toxins. Inactivates GTPases which alter actin cytoskeleton, disrupting barrier function and causing apoptosis as well as inflammatory response. Binary toxin CDT helps with barrier adherence.

Question 4

Virulence factors - Tetani

Answer 4

Tetanus toxin is activated by proteolysis and disulfide reduction and targets neurons.

Question 5

Virulence factors - Perfringens

Answer 5

Enterotoxin (CPE), lethal toxins (a,b,e,l)

Question 6

Virulence factors - Botulinum

Answer 6

botulinum neuorotoxin

Question 7

Pathogenesis - Difficile

Answer 7

antibiotics cause removal of protective microflora, allowing for Difficile to bind to the colon. From here it attaches to epithelial cells and releases toxins causing apoptosis and tissue damage. Reinfection is 20% likely due to antibiotics being the initial cause for infection.

Question 8

Pathogenesis - Perfringens

Answer 8

2 pathways. Perfringens will start as a spore and germinate after being cooked, producing an enterotocin. Once ingested, CPE will attack tight junctions, leading to intestinal hypersecretion and fluidity of gut contents. Second pathway – if infected trauma would will use lethal toxin a to reduce blood flow at wound and allow for anaerobic growth. Phospholipase-C (part of lethal toxin a) will cleave the phosphate head off cell membranes and therefore cause apoptosis. If lethal toxin B is present, necrotic enteritis will also occur.

Question 9

Pathogenesis - Tetani

Answer 9

tetanus toxin enters neuromuscular junction and enters inhibitory interneuron which is responsible for monitoring activity of lower motor neurons. Tetanospasmin blocks inhibitory signals and vesicle release by cleaving syanptobrevin-2 receptor. This causes hyperstimulation

Question 10

Pathogenesis - Botulinum

Answer 10

botulinum neurotoxin blocks excitatory neurotransmitter acetylcholine release from motor neurons which leads to flaccid paralysis. Cleaves synaptobravin-2 but has opposite effect due to it acting at the neuromuscular junction.

Question 11

How are the 4 types of Clostridium detected?

Answer 11

Difficile: faecal samples
Perfringens: testing on wounds, faecal samples
Tetani: physical exam
Botulinum: physical exam

Question 12

How are the 4 types of Clostridium treated?

Answer 12

Difficile: antibiotics are first option. If relapse occurs, faecal transplant is promising to restore healthy normal flora.

Perfringens: surgery and penicillin for wound infections. Hyperbaric oxygen can be used to try and suppress growth. Food poisoning is self-limiting and just needs fluid replacement.

Tetani: immunisation, antibiotics, antitoxin if it hasn’t reached nervous system, sedation of muscle spasm.

Botulinum: antitoxins taken with supportive care. 25% mortality rate