HAI - Clostridium difficile Flashcards
What is clostridium difficile?
A typically commensal bacteria found in the guts of children, and in low amounts in some adults (asymptomatic carriage)
What are the main toxins that Clostridium difficile produce?
ToxA (308 kDa enterotoxin)
ToxB (270 kDa cytotoxin)
What are the steps in toxin mechanism?
Attachment
Endocytosis
Acidification of vacuole
Release of enzymatic domain
Action on GTPases
Summarise toxin attachment and endocytosis
Toxins bind to specific receptors on host intestinal epithelial cells. Toxins are internalised into the host cell via endocytosis, forming an endocytic vesicle
Summarise acidification of vacuole and release of enzymatic domain
Endocytic vesicle undergoes acidification, which is necessary to allow translocation of their enzymatic domain into host cell cytoplasm
Summarise action of toxins on GTPases
The enzymatic domains of the toxins glucoslyate small GTPases such as Rac and Rho, resulting in their inactivation. This disrupts various cellular processes, including actin cytoskeleton organisation
What is the result of the disruption of actin cytoskeleton organisation?
Damages the absorptive surface of the interstinal epithelium. This impairs nutrient absorption, and contributes to diarrhea
What can occur as a result of the toxins in severe cases?
Pseudomembraneous colitis: - Plaques of nectrotic tissue slough from colon - Can be fatal
In what environments does C. difficile thrive?
Less diverse microbiota. Therefore use of antibiotics allows it to thrive.
What often happens when antibiotics are used to treat C. difficile?
Antibiotics kill them, however the spores produced by C. difficile remain, so when antibiotic treatment ceases, the spores can germinate again, causing another infection
What is ribotype 027?
A fluroquinolone resistant type of C. difficile
