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Clostridium difficile pathogenesis

Carlyle Laurent Bacterial Pathogenicity L3 Englisch 144 Karten

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  1. 1C. difficile is a Gram (positive/negative) obligate __________positive, anaerobe
  2. 2C. difficile causes a spectrum of diseases collectively known as:CDAD
  3. 3The diarrhoea that C. difficile causes is:self-limiting, recurring
  4. 4C. difficile an cause Pseudomembranous colitis, where:Yellow plaques form (essentially blisters full of neutrophils) that can cause death if not treated quickly
  5. 5C. difficile can cause toxic megacolon where:The colon becomes severely inflammed, the only treatment is removal of the bowel, will most likely lead to death
  6. 6C. difficile is the leading cause of _____________________________ world-wideHospital acquired infection
  7. 7C. difficile is most common in _________ populationselderly: but is increasing in younger populations like children and pregnant women
  8. 8C. difficile affects all _____________ and also _____________mammals, chickens
  9. 9The associated health care costs for C. difficile infection could be as high as:$4 billion a year in the US
  10. 10C. difficile usually colonises infant humans when they are born, which leads to:nothing. normally don't get disease. Reasons are unclear
  11. 11It's very rare for a C. difficile infection not to be preceded by:antibiotic treatment
  12. 12C. difficile occupies its niche when:there is disruption of the normal gut flora
  13. 13C. diff spores germinate in the gut to form:vegetative cells
  14. 14C. diff toxins include:TcdA, TcdB
  15. 15C. diff is recognised as a gut commensal in about _% of healthy adults5
  16. 16Hypervirulent strains resistant to _____________ first appeared in Quebec and Philadelphia in the early 00s.Fluoroquinolone
  17. 17During the peak of the C. diff epidemic in ______, one ______ of all deaths in UK hospitals could be attributed to C. diff2007, half
  18. 18The 2000s epidemic was mostly caused by the ____ strain027: has since been brought under control, but ribotypes have increased in diversity since
  19. 19Since 2012, C. diff has accounted for about _______ deaths a year2000
  20. 20Hypervirulent strains produce a third toxin called:CDT
  21. 21Canadian and USA strains of 027 arose from ancestral strain ______________independently
  22. 22Epidemic ribotype 027 has a point mutation in ____ that makes it 500 fold more sensitive to ___________treR, trehalose
  23. 23Trehalose is:a disaccharide composed of 2 glucose
  24. 24Deletion of ___ genes results in a strain less able to kill animalstre
  25. 25Supplementation of media with ____________ in epidemic strains enhances virulencetrehalose
  26. 26Ribotype 078 has a new _-gene operon for trehalose metabolism4
  27. 27Dietary trehalose enhances virulence of epidemic Clostridium difficile is written by:Collins et al, 2018
  28. 28Both new North American strains acquired a mutation in ___ that increases resistance to fluoroquinolone, (but this is also found in non-epidemic strains)gyrA (Collins et al, 2018)
  29. 29Ribotype 078 prevalence has increased __-fold from 1995 to 200710 (Collins et al, 2018)
  30. 30Trehalose is used as a supplement in _____% of modern foods2-11.25 (Collins et al, 2018)
  31. 31Widespread use of trehalose in things like ___________________ coincides with:pasta and ice cream, C. diff outbreaks (Collins et al, 2018)
  32. 32All C. diff genomes encode a putative phosphotrehalase enzyme called ____ which is preceded by a transcriptional repressor called _____TreA, TreR (Collins et al, 2018)
  33. 33027 sensitivity to Trehalose is increased by:having a single point mutation in TreR that occurs near the highly conserved binding pocket (Collins et al, 2018)
  34. 34027 is ___ times more sensitive to trehalose500 (Collins et al, 2018)
  35. 35078 strains are more sensitive to Trehalose due to acquiring the following cluster of genes:PTS permease, a second phosphotrehalase, a putative glycan debranching enzyme TreX, and a second repressor (Collins et al, 2018)
  36. 36The ___________ found in 078 is both necessary and sufficient for growth on low concentrations of TrehalosePTS permease (Collins et al, 2018): deletion doesn't allow growth at 10 mM
  37. 37The second phosphotrehalase enzyme found in 078 shares __% amino acid identity with TreA55 (Collins et al, 2018)
  38. 38The second trehalose repressor found in 078 shares __% sequence identity with TreR44 (Collins et al, 2018)
  39. 39Mice with trehalose added to their diet in 027 models had higher _________ than those that didn'tmortality (Collins et al, 2018)
  40. 40Humans produce trehalase in the _____________, but high amounts of consumption allow Trehalose to reach ______________________small intestine, distal ileum and colon (Collins et al, 2018)
  41. 41C. difficile use __________ as a marker that they have colonised a mammalbile acids
  42. 42____________ is a prerequisite for difficile infectiondysbiosis
  43. 43Recurrent infection is best treated with:Faecal transplant
  44. 44Faecal transplant is still not widely used because:Squeamishness reduces compliance, infection risk is harder to screen for than blood, lack of trials
  45. 45One mixture of _ species as a probiotic has been shown to work as effectively as faecal transplant in mice6
  46. 46Faecal transplant has a __% cure rate93: meanwhile vancomycin has a 30% cure rate, and failures of faecal transplant on first attempt generally are cured on more attempts
  47. 47The process of Faecal transplant is:Screen donated samples for disease, blend donations, blended sample is passed through cheesecloth, sample is given to patient either by Enema or by Nasal-gastro tube
  48. 48Why in god's name is the nasal-gastro tube more widely used than an enema for Faecal transplants?The infection could have damaged the intestine, so avoiding the anal route is safer
  49. 49Rodent models of C. difficile infections are able to cure themselves by:eating each other's droppings
  50. 50Common Animal models for C. diff are:Golden Syrian Hamsters, C57BL/6 Mice
  51. 51Golden Syrian Hamsters are used to study the ______ phase of CDI where ______ are key virulence determinantsAcute, toxins
  52. 52Animal models are given ________ before being treated with C. diff sporesClindamycin
  53. 53Mice are used as a model for __________ stage of infectionColonisation: animals don't really get sick, much more humane than using the golden syrian hamsters
  54. 54Mice shed a lot of spores in:their faeces: "Super-Shedder State"
  55. 55The outermost layer of the spore is:Highly cross-linked protein
  56. 56Below the protein coat of the spore is:cortex peptidoglycan
  57. 57Cortex peptidoglycan differs from regular peptidoglycan in that:It is more tightly cross-linked, contains modified muramic Delta-Lactam residues that become targets for lytic enzymes protecting the rest of the cell wall
  58. 58Below the cortex peptidoglycan of the spore is:the original cell wall: AKA the "Primordial" cell wall
  59. 59Below the cell wall of the spore is:2 membranes
  60. 60Below the 2 membranes of the spore is:the core
  61. 61The core of the spore is _________, 25% __________, and protects DNA from:dehydrated, dipicolinic acid (proteins inside are acid soluble), UV damage
  62. 62_______ persist in health care facilities for long periods of timeSpores
  63. 63The spore forms as a result of __________ cell division, where:asymmetric, the septum is put closer to one pole as opposed to in the middle, and there is no increase in copy number
  64. 64The first step of sporulation after the septum is established is:membrane engulfs the forespore from behind
  65. 65After membrane engulfs the forespore from behind:a second membrane engulfs the forespore to from a free endospore in the middle of the cell
  66. 66In sporulation, the mother cell lyses after:formation of the free endospore
  67. 67In B. subtilis sporulation, _____ phosphorylation activates sigma _ in the forespore, which induces Sigma_ in the mother, which induces Sigma _ in the forespore, which induces Sigma_ in the motherSpo0A, F, E, G, K (Find Emma's Green Kimono)
  68. 68In clostridium, after SigmaF induces _______, the rest of the process is poorly understoodSigmaE
  69. 69Known germinants of C. diff sporulation include:Taurocholate, Glycine
  70. 70Stage 0 of sporulation cascade is:Vegetative cells
  71. 71Stage 1 of sporulation cascade is:Onset
  72. 72Stage 2 of sporulation cascade is:Commitment and Asymmetric cell division
  73. 73Stage 3 of sporulation cascade is:Engulfment
  74. 74Stage 4 of sporulation cascade is:Cortex formation
  75. 75Stage 5 of sporulation cascade is:Maturation and spore coat
  76. 76The final stage of the sporulation cascade is:Mother cell lysis
  77. 77If the ___________________ in sporulation is not controlled then there is loss of resistance in the final sporeorder of gene expression
  78. 78The final order of gene expression in sporulation is controlled by:using genes with promoters that are activated by specific sigma factors
  79. 79______ is the master controller of sporulation, and mutants don't sporulateSpo0A
  80. 80Upon sensing a germinant it takes ___________ to produce a vegetative cell90 minutes
  81. 81The most potent C. diff germinant is:Taurocholate
  82. 82Taurocholate is a ____________ made up of:Conjugated bile salt, Cholic Acid and Taurine
  83. 83Primary bile salts are synthesised in __________ and act to:the liver, emulsify fats: critical for uptake of fats and fat-soluble vitamins
  84. 84Secondary bile salts are produced via __________________________Bacterial metabolism in the colon
  85. 85Taurocholate gets processed to:Deoxycholate, Chenodeoxycholate, and cholate: Chenodeoxycholate inhibits growth of vegetative cells
  86. 86The spore is required for:persistence in the gut
  87. 87spo0A deletion mutants can only cause transmission if:faeces are eaten in mingling experiments
  88. 88TraDIS has been used to determine all the genes necessary for sporulation, which includes ___ essential genes. In total there are over ___ and the function of over ____ of these is not known.404, 798, half
  89. 89Factors implicated in the colonisation of pathogenic bacteria are:Surface/cell wall proteins, flagella, fimbriae, capsule, secreted proteins that can help create a niche they can colonise
  90. 90The S-layer makes up ____% of the total cellular protein10-15
  91. 91S. layers are found on up to __% of known bacterial species, and on every single ________90, archaea
  92. 92Functions of the S-layer include:Exoskeleton, Molecular Sieve, Adhesin
  93. 93The S-layer is typically anchored onto _____________ or ___Peptidoglycan, LPS
  94. 94C. diff S-layer can be stripped off with _____, because:Acid, the proteins aren't covalently attached
  95. 95Stripping off the S-layer results in 2 prominent bands:The Low Molecular Weight (LMW) band, and the High Molecular Weight (HMW) band
  96. 96The S-layer is mostly made of the protein ______SlpA
  97. 97After SlpA is expressed, it gets processed into:two pieces to create the LMW and HMW bands
  98. 98C. diff needs to make ____ copies of SlpA per second to maintain the S layer140: makes it the most expensive thing the cell is doing at any given time
  99. 99SlpA is very ____sticky: will adhere to cultured cells and ex vivo gut tissue
  100. 100SlpA is highly variable with over __ distinct sequence types known14
  101. 101In crystals HMW and LMW interact to form:a bridge
  102. 102_____ is a secretion ATPase essential for:SecA2, the S-layer
  103. 103All S-layer proteins share a __________ binding domain. In C. diff each has _ copies that fold together to make a ________ domainCell Wall, 3, triangular
  104. 104Cleaved SlpA is transported out of the cell via:SecA2 and SecYEG
  105. 105Avidbiotics developed ________, a new therapeutic that resembles:Avidocin, the tail of a contractile bacteriophage without the capsid head.
  106. 106Avidocin works by:pentrating the bacterial envelope to destroy ion potential
  107. 107Avidocin is originally produced by:C. diff to kill other strains
  108. 1081 in a billion C. diff are naturally resistant to Avidocin because:they lack an S-layer: turns out its not that essential
  109. 109Mutants that resist avidocin by lacking an S-layer are capable of:reverting the mutation to have an S-layer again: "revertants"
  110. 110Avidocin resistance comes about by the mutation:1bp instertion or substitution that introduces a premature stop codon in SlpA
  111. 111S-layer lacking mutants are sensitive to:Lysozyme and LL-37
  112. 112____ introduces pores and is made by every cell in the:LL-37, GI tract
  113. 113C. diff with functional S layers are normally highly resistant to LL-37, despite the fact that:it is definitely small enough to get through the pores in the S-layer: It could be sequestered by charged structures
  114. 114S-layer mutants have trouble producing ________, and complementation restored thisspores: the spores it did produce appear immature
  115. 115Spores produced by S-layer mutants have ___% viability after being held at 75C, compared for __% for wild type0.2, 50
  116. 116S-layer mutants are entirely avirulent in ________Hamster: 100% survival in 2 weeks with no diarrhoea, weight loss, or fever
  117. 117S layer mutants still colonised hamsters but:didn't produce enough toxin to cause disease
  118. 118biogenesis and functions of bacterial S-layers is written by:Fagan et Fairweather, 2014
  119. 119SlpA diversity can affect:efficacy of antibodies (Fagan et Fairweather, 2014)
  120. 120Bacterial S-layers are usually composed of:single proteins (Fagan et Fairweather, 2014)
  121. 121Diversity in C. diff S-layers is likely caused by:recombination between S-layer cassettes (Fagan et Fairweather, 2014)
  122. 122Secretion of SLPs involves:a dedicated Secretion system (Fagan et Fairweather, 2014)
  123. 123Functional heterogeneity of S-layer includes:Biogenesis of the cell wall, Control of cell division, Swimming, Permeability barrier, adhesion, immune evasion, in some species no known function (Fagan et Fairweather, 2014)
  124. 124HMW and LMW SLPs induce the release of pro-inflammatory cytokines from human monocytes like:IL-12, TNF-alpha, IL-10, activation of dendritic cells dependent on TLR4 (Fagan et Fairweather, 2014)
  125. 125TcdA is ___ kDA308
  126. 126TcdB is ___ kDa270
  127. 127TcdB is cleaved by incubation with cultured animal cells to yield:a 60 kDa fragment as N-terminal glycotransferase
  128. 128Protease for TcdB cleavage has not been identified but the process does require:Ins6P
  129. 129TcdA and B share a common structure in that:they have an N-terminal Enzymatic region, a middle translocation(?) domain, and a C-terminal receptor binding domain (until recently there has been some debate as to what the middle region does)
  130. 130The receptor binding domain of TcdA and TcdB consists of:Alternating long and short repeats (less in TcdB than in TcdA)
  131. 131The translocation domain of TcdA and B is highly ____________, suggesting it could be:hydrophobic, membrane spanning: could form a pore to allow toxin entry into cell
  132. 132Enzymatic domain of TcdA and B work by:glucosylating small GTPases like Rho, Rac, and Cdc42
  133. 133Ultimately TcdA and TcdB cause:cell rounding due to collapse of actin
  134. 134Disruption of actin by TcdA and B causes:cytoskeleton changes, disruption of tight junctions, accumulation of neutrophils (hence the plaques in pseudomembranous colitis), production of inflammatory mediators, inflammation
  135. 135TcdA and B are encoded on the:Pathogenicity locus (PaLoc)
  136. 136The PaLoc encodes:tcdD, tcdB, tcdE, tcdA, tcdC in that order (Damn, Brendon eats aged Cats.)
  137. 137TcdD encodes:an RNA polymerase Sigma factor that positively regulates the PaLoc. TcdD is required for tcdB and A expression
  138. 138Once pathogenesis starts, ____ is on a positive feedback loop to upregulate its own expressionTcdD
  139. 139TcdE encodes:noone's really sure. Resembles a holin, which are proteins that help release toxins by lysis, but they don't do that in C. diff
  140. 140TcdC encodes:A membrane localised anti-sigma factor. A putative negative regulator for toxin expression that binds to TcdD to prevent its action
  141. 141TcdC is modified in hypervirulent 027 strains in that:it has an 18bp deletion
  142. 142TcdA and B toxins enter the cell via:Clatherin mediated endocytosis: makes the membrane bud inward
  143. 143The vesicle that brings in TcdA and B gets acidified, which prompts:refolding of tranlocation domain to allow it to form a pore (hasn't been directly observed)
  144. 144Catalytic domain of TcdA and B is performed by a:Zinc metalloprotease

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L3 Bacterial Pathogenicity Karteikarten am Clostridium difficile pathogenesis, erstellt von Carlyle Laurent am 31/05/2018.
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