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63 Cards in this Set
- Front
- Back
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What is a capsule?
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Loose network of polysac that covers the surface of capsulated bacteria
-Repeating saccharide units linked by glycosidic bonds |
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How are capsule diverse?
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Differ by:
-Nature of repeating saccharide units -Nature of glycosidic bonds (1-2, 1-4, 1-6 etc) -Introduction of branches between chains -Substitutions with acetyl or phosphate gps |
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How many capsular serotypes does E. coli have?
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80 capsular serotypes (K Ag)
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What are some major G+ pathogens that produce capsules?
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S. aureus (8)
Strep pneumoniae (90) Gp A sterptococci Gp B streptococci (9) Enterococci |
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What are some major G- pathogens that produce capsules?
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Neisseria meningitidis
Klebsiella pneumoniae (77) E. coli (80) Haemophilus influenzae (6) Pseudomonas aeruginosa Salmonella typhi |
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Does S. typhimurium have a capsule?
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No
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Check figure pg 2
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check figure pg 2
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What are the fcts of bacterial capsules?
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-Protection from desiccation
-Adherence -Resistance to complement-mediated killing -Trap AMP -Molecular mimicry |
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How is a capsule used in adherence?
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Capsular polysac may help adhere to srfaces or other bacteria
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How does the capsule help in resistance vs complement killing?
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Capsule masks the underlying cell surface structure
Capsule can't prevent binding of C3b, but prevents interaction of the bound C3b with phagocyte receptors |
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How does the capsule trap AMP?
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Capsule negatively charged and is attracted to the AMP
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What is molecular mimicry?
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Capsular polysac can mimic host Ag (fucose, on all host cell surface, surface molecule of intestinal epithelial cells)
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Describe the Vi capsule of S. typhi.
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-135-kb DNA region (SPI-7: Salmonella pathogenicity island-7)
=>this is absent from the S. typhimurium genome -DNA region in SPI-7 is the viaB locus -This encodes ptns for biosynthesis and export of the Vi capsular Ag (middle) |
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Describe the Vi Ag
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Linear polymer of alpha-1,4 (2-deoxy)-2-N-acetylgalacturonic acid
Vi is variousl O-acetylated at the C-3 position |
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What does S. typhi cause?
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Typhoid fever
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Describe typhoid fever
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Systemic
Goes through intestine |
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What is the SPI-7 responsible for?
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Capsulatef transport out of the cell
(S. typhimurium doesn't have this pathogenicity island .: stays in the intestine) |
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Describe the synthesis and export of serotype K30 capsule in E.coli
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Repeat units of the polymer are assembled on a lipid acceptor (udecaprenol diphosphate, und-PP), in the cytoplasm
-und-PP-linked repeat units are "flipped" across the inner mb by Wzx -Polymerization occurs at the periplasmic face and is dependent on another integral mb ptn, Wzy -Wzy-dependent polymerization requires the activity of the tetrameric Wzc ptn -Wzb is a ptn tyrosine phosphatase enz responsible for deP Wzc -The cycling P of Wzc is crucial for export -Wza and Wzc ptns interact to form a complex that spans the periplasm Look at pic pg 4 |
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Which bacteria is iron not essential for?
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Borrelia burgdorferi (lyme disease)
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What does Boreelia use instead of iron?
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Manganese
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What is iron required for in bacteria?
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Some essential ptns need iron as a cofactor
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What does Fe3+ bind to in mammals?
Why? |
Binds to:
hemoglobin ferritin (cytoplasmic ptns) transferrin (serum) lactoferrin (mucosal secretions) Fe3+ is insoluble .: binds to ptns |
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Can the concentration of free ferric iron at pH7 sustain bacterial growth?
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No (only 10^-18M)
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How do bacteria acquire Fe3+?
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Synthesis and secretion of low MW Fe3+ -chelating compounds
=> Siderophores |
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Where are siderophores found?
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G+ and G- bacteria
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What part of the enterobactin interacts with iron?
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6 O2 from 3 diphenolic gps
(different structure with and without iron) |
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How do G+ bacteria take up iron?
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Siderophores are expopted from the bacteria
Siderophores bind iron outside the cell Siderophore bound to iron binds binding protein and enters the bacteria through an ABC transporter (ABC transporter requires ATP) Use ferritin binding proteins to get iron and then its transferred to siderophore) Once inside the cell, iron is released from the siderophore Siderophore exists cell |
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How do G- bacteria take up iron?
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Siderophores released into surrounding env't
Bind iron Enter bacterial Outer Mb throug a receptor (doesn't require ATPase to enter, but need E for conform change of Ton B) Once in periplasm, siderophore-Fe3+ goes through ABC transporter Siderophore releases Fe3+ Fe3+ reduced to Fe2+ |
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What happens to the siderophore after it delivers the iron?
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Can be recylcled or degraded
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What provides the E required for conformational change of TonB?
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PMF
H+ goes from periplasm to cytoplasm (across inner membrane) |
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What is an endotoxin?
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LPS components of G- bacteria
-term used to distinguish toxic substances that were released after bacterial lysis as opposed to exotoxins, which are secreted from live bacteria |
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Describe the endotoxin/lps structure?
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"O" side chains (oligosac): species/serotype Ag (i.e. all E. coli strains will have this)
Core polysac: genus specific Ag (i.e all a genus will have this, all escherichia will have the same one) Lipid A: toxic moiety, interacts with TLR4 |
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What part of this structure contains the hydrophobic region of LPS?
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Lipid A
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Describe Lipid A.
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Has 2 P NAG molecules with 6 FA (in E. coli) attached (C12, C14 and C16)
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Describe the FA in lipid A
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Usually saturated
Some directly attached to NAG molec Some esterified to the 3-hydroxyl gp of FA |
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What is the toxic portion of LPS?
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Lipid A
Look at slide, pg 7 |
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What happens if purified lipd A is injected into an animal?
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Same response as if injected entire LPS
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Describe how Lipid A in G- bacteria are structurally diverse.
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Can have different # of FA
Usually have 6, but can have 5 FA attached to different length C-chains (12,14 or 16) C12: Laureate C14: Myristate C16: Palmitate |
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Which are more potent TLR4 activators: hexa-acylated lipid A or tetra-acylated lipid A?
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Hexa-acylated gps are more potents
Can cause septic shock -> Look at pg 7, bottom for different types of bacteria |
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What kind of lipid A does E.coli have?
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6 FA
14C or 12C |
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What kind of lipid A does P. aeruginosa (cystic fibrosis form) have?
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6 FA
12C and 16C |
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What kind of lipid A does P. aeruginosa (non-cystic fibrosis form) have?
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5 FA
12C |
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What kind of lipid A does S. thyphimurium have?
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6 FA
12, 14, 16C ->Usually 6Fa but can have a 7th thats a palmitate) |
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What kind of lipid A does H. pylori gave?
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4 FA
16C Doesn't activate TLR4 because doesn't want to kill host |
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What kind of lipid A does does Y. pestis have?
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4 FA
LPS depends on T ->If higher T, more toxic |
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Describe the O polysac.
Look at pg 8 (missing flashcards for pg 8) |
Attached to the core polysac
Made of repeating oligosac units of 3-5 sugars Varies in length from 0 -50 repeating units O-polysac is the antigenic part of the sugars |
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How many different O serotypes does E. coli have?
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167
-> great variation in the nature of sugars in the O-polysac btw bacterial strains ->Enterobacteria also have many O-polysac with different chain lengths |
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Which bacteria do not have O polysac?
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N. gonorrhoeae
N. meningitidis: Pretty short LOS C. trachomatis: v/ short LOS ->These only have the core polysac and Lipid A => these forms of the endotoxin are called lipooligosac (LOS) |
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How is lipid A trasnported to the OM?
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ABC transporter MsbA flips nascent core-lipid A to the outer leaflet of IM
In WT E.coli (not K-12), O-Ag is ligated to core-lipd A on the outer surfae of IM ABC transporters LptBFG, working with LptC and the periplasmic ptn LptA, translocates LPS to inner leaflet of OM LptDE (lmp/RlpB) flips LPS to the outside of the cell |
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Which bacteria modify lipid A?
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S. typhimurium
P. aeruginosa Y. pestis Shigella flexneri |
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What regulates these modifications of lipid A?
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Environmental signals
(T for Salmonella) (Mg3+/AMP for yersinia) |
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What are these modifications of lipid A responsible for/what do they cause?
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Resistance to AMP (antimicrobial peptides)
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Describe AMPs
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Important part of innate immunity
Diverse in sequence/structure Amphipathic structure Net + charge: cationic peptides |
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What are the fcts of AMPs?
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Antibacterial properties: AMPs interact with the bacterial mb and permeabilize the mb (need a certain [peptide] )
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Why are AMPs attracted to bacterial mbs?
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Bacterial mbs have anionic phospholipids that attract +vely charged AMPS
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How is lipid A modified in S. enterica?
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-Adds 4-aminoarabinose and/or pmrE/pmrF
-Addition of palmitate (pagP) -Deacylation of lipd A at position 3 (pagL) -Hydroxylation of FA (lpxO) |
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What is the effect of LPS modifications on resistance to AMPS?
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-Decrease electrostatic interactions btw lipid A and AMPs
-Probably decrease the permeability of LPS to AMPs (palmitate C16) (Would .: need much higher [AMP] to kill the bacteria) |
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How are LPS modifications controlled?
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2-component regulatory system
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Describe the 2-component regulatory system
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Respond to env't signals (Low [Mg2+], AMPs, acidic pH)
Sensed by PhoQ PhoP P Activation of PmrA/PmrB system (transcribe pmrD: codes for a ptn that acts on another system) Transcribe mgtA: Mg2+ transport T mgtCB: Mg2+ transport, intramacrophage survival T pagP: LPS modifications, resistance to AMPs phoPQ: T regulation |
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What does pmrD go on to act on?
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PmrA/B system
PmrA is P T pbgP==> pbgE and T uhd -> both cause LPS mods that allow resistance to polymyxin B T pmrCAB: T regulation |
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What does PhoQ do?
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Sense AMPs
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Describe PhoQ
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On bacteria
Flat surface that comes close in contact with mb Highly negatively charged surface that participates in binding AMPs cuz its negatively charged, is repulsed by mbs that are also neg charged ->If a peptie is +vely charged, interacts and activated PhoQ which P PhoP Start making LPS |
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How does Salmoenlla use PhoP/PhoQ?
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Used to evade innate immune system
-S. enterica senses some AMPs PhoQ sensor kinase binds AMPs Binding of CAMPs to PhoQ results in LPS modifications and resistance to AMPs ->Get modification of Lipid A in LPS -> Bacteria become more resistant to AMP |
