GITI Flashcards
What are the characteristics of a GI infection?
1) food acts as a vehicle for transmission: food handlers contaminate the food and consume the pathogen
2) toxins may be present in the food
3) Broad-spectrum antibiotics disrupt normal gut flora causing over growth of pathogens
What are the characteristics of C.Difficile?
-gram positive rod
-strictly anaerobic
-spore forming
How do spore forming bacteria grow?
1) divide by binary fission
2) when nutrients are depleted, spore formation is initiated
3) dna condenses and aligns itself in the middle of the cell -> becomes known as the mother cell
4) Dna divides and forms forespore which is engulfed by mother cell
5) Protein coat forms around spore, spore is released from mother cell
What are the risk factors for C.Diff?
- spores: persistent and transmissible, resistant to antimicrobials
- hospitalisation and BS antibiotic use, hygiene, contaminated equipment
Why can C Diff spores pass through the stomach?
They are highly resistant to stomach acid
What happens to C Diff spores after they reach the small intestine?
- the spores encounter favourable conditions: bile salts, mildly acidic PH
- this triggers germination of spores -> produces C Difficile vegetative cells which are metabolically active
Which toxins do vegetative C Diff cells produce and what affect do they have?
- Toxin A (enterotoxin) and B (cytotoxin)
- damage lining of the colon: inflammation, diarrhoea, pseudomembranous colitis (severe inflammation and ulceration of colon)
How are C Diff spores spread from the patient?
- C Diff cells in colon produce spores which are secreted in patients diarrhoea
- highly resistant
What are the 3 main steps in germination?
- spores lose their heat resistance and release ions as well as calcium stored in their heat complex
-the spores core absorbs water and enzymes breakdown the cortex and other protective proteins
-this reactivates its metabolism -> metabolically active - makes it sensitive to antibiotics
How does C Diff carry out cell adhesion?
- it has S layer proteins which attach to the cells lining the gut -> adherence is essential for bacteria to establish an infection
- flagella allows It to reach areas in the gut
Where are toxin A and B encoded onto?
Pathogenicity Locus (PaLoc)
What is the mechanism of action for Toxins A and B?
- modify Rho GTPase proteins which are important for maintaining the structure and function of gut lining cells (regulate tight junctions and actin filaments)
- cause actin filaments to break down and lose structure -> cells lose shape and attachment = apoptosis
- stimulate cytokine production, leading to inflammation -> diarrhoea and colitis
What symptoms occur when tight junctions are weakened and why do they occur?
- diarrhoea and inflammation: toxins, bacteria leak through the gut lining due to toxins A and B inactivating Rho proteins
What are the key features of C Difficile ribotype 027?
produces higher than normal levels of toxin A and B
-causes base pair deletion in toxin regulating gene -> makes it more deadly
- resistant to ciprofloxacin and moxifloxacin
What is the function of the positive regulator gene in PaLoc?
- activates the expression of tcdA and tcdB which promotes Toxin A and B production
-a protein porin in PaLoc is associated with the release of these cells into the environment - downstream regulator in PaLoc prevents excess tcdA and tcdB from being produced
