Clostridium Difficile II Flashcards
Is clostridium difficile overgrowth after antibiotic treatment simply due to an opening up of niches?
No there are also important functions performed by the commensal bacteria which are lost
What are the functions performed by commensal bacteria in the gut which prevents clostridium from overgrowing?
Normal gut microflora convert biosalts to secondary bile salts, this prevents spore germination as primary bile salts act as a signal for germination
Toll-Like Receptor 5 signalling from flagellen helps to maintain epithelial barrier integrity
What are the hypervirulent strains of Clostridium dificile?
NAP1/BI/027 Strains
What are the features of hypervirulent strains of C.Diff?
The sporulate with higher effiency, produce more toxin, produce binary toxin, resist fluroquinalones due to mutations in DNA gyrase genes
How are the toxins produced by the hypervirulent strains of C.Diff different to the normal strains?
The amino acids in the protein are highly similar however they differ in receptor binding ability, the hypervirulent strain is less selective with regards to what receptor it binds, has a higher potency and enters cells more rapidly
What is the most relevant model C.Diff disease?
Mice that were infected with C.Diff, and then treated with antibiotics allowing overgrowth of the bacteria
What happened to the most relevant mouse model infected with C.Diff?
Different mice behaved differently with some mice able to clear the infection to just above the detectable levels while other mice became supershedders, continuing to release spores at high levels
What occurs in C. Diff shedding in the carrier state?
There is a complex microbiota, low spore excretion and low transmission
What occurs to C. Diff shedding in the supershedding state?
This state is triggered by antibiotics and results in a simplified microbiota with high spore excretion, high transmission and epithelial damage
What is the key transcriptional regulator for spore transmission in bacillus?
Spo0A
What is the effect of giving an inhibitor of Spo0A to a patient infected with C. Diff?
This inhibits sporulation and thus reduces transmission however there seems to be a time limit of the inhibitor must be given at least 9 hours after the antibiotic
How can a faecal microbiota transplant provide treatment to a C. Diff infected patient?
It can restore the normal microbiota, returning their functions which inhibit spore germination in C. Diff
How is a faecal microbiota transplant undertaken?
The healthy stool from a donor is instilled through a nasogastric tube or a gastroscope or a colonoscope or a retention enema
