micro 6 Flashcards
what is shiga toxin producing e.coli also known as?
•Verocytotoxin producing E. coli
what is a subset of shiga toxin producing e.coli?
- A subset of these can be called EnterohemorrhagicE. coli (EHEC)
- All EHEC are STEC but not all STEC are EHEC
how infectious is STEC?
- STEC infectious dose is low
* Believed to be <100 cells (some say <10)
what are the two main variants of STEC?
2 main variants Stx1 andStx2
are the STEC variants the same?
•Antigenically different but same mechanism of action
what are the STEC variants used for?
Used as markers for identification (PCR/multiplex PCR
what is STEC associated with?
Associated with hemorrhagic colitis and hemolytic-uremic syndrome.
what was the first iscolated STEC?
E.coli 0157:H7
how can E.coli 0157:H7 be spread?
- Major foodborne pathogen
* Can be spread person-person through faecal shedding
what are STEC 0157 ?
refers to EC strains which are 0157 but not necessarily H7 variants
what are shiga toxins and where are they most commonly found?
- Family of toxins that are most commonly found in Shigella dysenteriae and some STEC serotypes
- Extremely potent bacterial toxin
what are the two units which shiga toxins are composed of?
- Comprised of 2 units
* A (1 copy)•B (5 identical copies)
how does shiga toxin producing e.coli work?
- Bacteria binds to cell surface a)Intimin protein
- B subunit binds to glycolipic globotriaosylceamide (Gb3)
- Internalised within an endosome
- Transported to Golgi a)A1 subunit is cleaved from B pentamer
- Inhibits protein synthesis
- Cell death
what was clostridioides difficile known as?
•Was originally Clostridium difficile•Technically renamed in 2016
what is c. difficle known for?
One of the most important healthcare associated MDR pathogens- NOT TRAVLERS DIAHORREA
does c. difficile form spores?
- It forms SPORES and is ANAEROBIC!!•Lets it resist disinfection
- Cant survive in oxygen
what is a way of subdividing strains based on the 16S-23S intergenic spacer region?
C. diff ribotypes
what strain of the c. difficle causes the most severe disease?
•027 ribotype causes more severe disease
what are c. diff toxinotypes?
are a group of strains that have changes in the toxin A and B coding region
•Known as PaLoc(Pathogenicity locus)
how are c. diff ribotypes and toxinotypes done?
•Done by looking at PCR restriction fragment length polymorphism
which toxinotypes have small and large variations?
- Toxinotype III has small variations
* Toxinotype X and XVII have large deletions in tcdA
are c. diff spores metabolically dormant?
yes-•Can resist disinfection and environmental stress
what are the differnt layers of a C.diff spore?
•Core (A)•Contains supercoiled DNA bound with SASPs•Partially dehydrated•Contains up to 1M Ca-DPA
- Inner membrane(B)
- Permeability barrier against chemicals
- Germ Cell Wall (C)
- Becomes the cell wall after germination
- Cortex (D)•NAM modified →muramicacid-delta lactam
- Outer membrane (E) and spore coat (F)•Predominantly Glyoproteins
- Exosporium(G)•Plays a role in host pathogen interactions
what effect do antibiotics have on c. diff?
- Use of broad spectrum antibiotics can disrupt normal microflora
- Removes competition allowing C. diff to grow
how is c. diff associated infection treated?
- Infection usually treated with antibiotics•1 in 3 may have relapse
- Type of antibiotic may have an influence
how do c. diff germinate? and where?
C. diff spores have to enter the body and transit to an anaerobic environment •Shown to germinate in the small intestine
what does c. diff require in order to germinate?
- Requires a “signal” in order to germinate
- Primary bile salt taurocholate can induce germination (in vitro)
- Other primary bile salts also able to cause germination
- Secondary bile salts shown to inhibit C.diff
what is the c. diff clinical spectrum and how is it graded?
- Asymptomatic carriage
- Non-toxigenic forms of C. diff•Toxin neutralising antibodies
- Diarrhoea•Watery diarrhoea ≥3 times a day•5-7 on Bristol stool chart
- Colitis and pseudomembranous colitis•C.difftoxinsattack colon epithelial cells causing damage•Produces an inflammatory response
- Toxic megacolon•About 0.4-3% of all C.diffcases•38-80% mortality•Characterised by highly dilated colon, bloating- most severe
what are the two main toxin strains produced by c. difficile?
•TcdA(enterotoxin) and TcdB(cytotoxin)
what do different strain of c. difficile do? A-D
A: Biological Activity: N-terminus containing glucosyltransferase domain; Acts on small GTPasesinvolved in cytoskeleton regulation
B: Binding: 37 or 19 repeats of oligopeptides at C-terminal; Involved in receptor binding
C: Cutting: Cysteine protease domain; Promotes autocatalytic cleavage of toxin
D: Delivery: delivery domain; Involved in translocating toxins into cytosol
what does the 027 ribotype produce?
produces Cdt(a binary toxin) •Also produces more TcdAand TcdB(16 and 23 fold respectively)
what is c. diff toxins mechanism? A and B
- Toxin binds to host receptor
- Internalised via endocytosis
- Endosome acidified and pore formed
- GTD released into cytoplasm
- Glycosylation of Rho GTPases
- Cytotoxic and Cytopathic effects
What is the C. diff CdT toxin mechanism?
- Toxin binds to host LSR receptor
- Internalised via endocytosis
- Endosome acidified and pore formed by CdtBand CdtAreleased into cytoplasm
- Cdtainhibits actin polymerization near cell membrane
- Fibronectin microtubules elongated and project through microvilli →↑ C. diff attachment
what is the c. diff treatment?
- 1stepisode of mild to moderate infection, •Oral metronidazole 400mg every 8h for10–14 days•Metronidazole Intolerance: oral vancomycin 125mg every 6h for 10 days
- 2ndepisode of infection ORsevere infection ORinfection not responding to metronidazole •Oral vancomycin•Can be replaced by Fidaxomicin•Suggested duration of treatment 10–14 days
- For infections which don’trespond to vancomycin or fidaxomicin•Oral vancomycin & IV metronidazole•Suggested duration of treatment 10–14 days•Can be adapted based on patient type
what are the NICE recommendations for faecal transplantants?
hould only be considered for patients with recurrent C. difficileinfections that have failed to respond to antibiotics and other treatments.
- encourages further reasearch
