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91 Cards in this Set
- Front
- Back
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Which E. coli strains have we seen so far that aren't invasive?
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ETEC: LT (like cholera toxin), ST
EAggEC: distinctive adherence, toxins |
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Which strain is invasive?
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EIEC (like Shigella), actin-based motillity
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What does EPEC use to make pedastal?
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T3SS
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Why does EPEC destroy tight jcts btw epithelial cells?
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So it can go further into the body and reach the tissues
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What host ptn forms tight jcts?
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Occludin
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Which effectors cooperate to disrupt tight jcts?
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EspF
Map NleA etc |
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What happens if one of these effector's are knocked out?
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Tight jcts can't be disrupted
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How does EPEc cause disease once it attaches?
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Effacement of microvilli: loss of absorptive surface
Destruction of tight jcts btw intestinal epithelial cells Signall transduction in host cells Alterations in water and elcetrolyte absorption and secretion |
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How did EHEC (enterohemorrhagic) arise?
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When EPEC strain acquired shiga toxin from shigella dysenteriae through a bacteriophage
(EIEC doesn't encode shiga toxin, just has a similar toxin. EHEC does encode the Shiga toxin) |
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What does this show?
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How bacteria become increasingly pathogenic
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What disease does EHEC cause?
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Hamburger disease
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What is the major reservoir for EHEC?
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Cattle
-> Asymptomatic carriers of EHEC in their intestines -EHEC is shed in manure and can contaminate meat during slaughter -Usually ass't with ground beef, manure contaminated produce and water |
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What's the difference btw EHEC and regular E. coli strains?
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EHEC has extra DNA, including pathogenicity islands and virulence factors
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Describe EHEC pathogenesis.
How is it similar to EPEC.? How is it different? |
Similar to EPEC:
LEE pathogenicity island T3SS Pedastal formation (Tir) Tight jct disruption Different from EPEC: Shiga toxin |
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What kind of a toxin is the Shiga toxins?
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AB toxin
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What does the B subunit do?
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Binds the glycolipid globotriaosylceramide (Gb3), a lipid on the cell surface
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What is the A subunit?
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Cleaves rRNA, causing an arrest in ptn synthesis
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Where are the receptors for the shiga toxin?
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Kidney
Intestinal cells |
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What does the shiga toxin lead to?
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Kidney damaga
Hemorrhagic colitis |
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Where is the gene that encodes shiga toxin?
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on a temperate phage that is inserted into bacterial CHR
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Is the pedastal formation the same for EHEC and EPEC?
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No
EPEC: needs Nck adaptor ptn to make the pedastal EHEC: has adapted a way to make pedastal without host tyr-P |
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What happens if Tir is deleted in EPEC or EHEC?
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No pedastal formation
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What happens if Tir is deleted in EPEC, but it is in the presenceof an EPEC that has Tir?
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Pedastal formation
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What happens if Tir is deleted in EHEC, but it is in the presenceof an EHEC that has Tir?
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Pedastal formation
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What happens if Tir is deleted in EHEC, but it is in the presenceof an EPEC that has Tir?
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Pedatal formation
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What happens if Tir is deleted in EPEC, but it is in the presence of an EHEC that has Tir?
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NO pedastal
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What does this tell us?
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That EHEC tir requires other EHEC encoded factors to work (unlike EPEC)
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What is the EHEC encoded factor required for pedastal formation?
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EspFU (similar to EspF, encoded in prophage U)
-> without this, can't make pedastal |
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What does EHEC bind?
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Binds and activates N-WASP
Basically does what Nck does, but its a bacterial ptn, not a host ptn EspFu doesn't bind Tir directly, another factor btw them |
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How does EspFu activate N-WASP?
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Directly
N-WASP normally auto-inhibited Cdc42 bind GDP-binding domain on N-WASP, releases it from VCA, relieves auto-inhibition -> Can now work to stimulate activity |
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How doe EspFu activate N-WASP?
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Mimics domain that auto-inhibit
Replcaes GBD, competitively releases VCA domain ->EspFu mimics VCA domain, forces it open, turn on host cell path |
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What is the host ptn that binds Tir and EspFu?
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IRSp53/Irtks
Binds both Tir and EspFu simultaneously ->1st ex of bact/host/bact sandwich |
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What is an example of EHEC illness?
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Hemorrhagic colitis: watery diarrhea leading to bloody diarrhea
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What is hemolytic uremic syndrom?
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Hemolytic anemia
Renal failure (most common cause of acute renal failure in kids) thrombocytopenia (decrease in platelets, tissue hemorrhage) Can lead to permanent loss of kidney fct Fatality: 3-5% 25% of HUS patients have neurological symptoms 50% of HUS patients have chronic renal problems |
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What toxin cause HUS?
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Shiga toxin
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Is EHEC getting more virulent?
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Variations within the EHEC O157:H7
->divided into clades |
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Whare clade strains are ass't with being more virulent?
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Clade 8 strains
-> Probably required new virulence factors or one of its virulence factors have been tweaked |
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How can EHEC be treated/prevented?
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Shouldn't use antibiotics (releases toxin)
NO lomotil/imodium Rehydration therapy Handwashing Cooking hamburger meat Keep raw utensils seprate from cooking ones Wash produce Pasteurization for milk/juice Future: vaccination of cattle |
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What are extraintestinal E. coli infections?
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UTIs
Meningitis Sepsis ExPEC (Extraintestinal pathogenic E. coli) |
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What kind of UTIs can E. coli cuase and it waht proportion?
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Community acquired infections: 50-70% of these due to E. coli
Nosocomial infections: 50% cuased by E. coli |
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Which E. coli cause community-acquired UTIs?
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UPEC (uropathogenic E. coli)
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Describe community acquired UTIs
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Caused by 6 E> coli serogps
80% of infections are in women Recurrent infections common |
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Where does UPEC colonize?
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First colonizes the bowel, then moves to the urethra
(starts in the intestine, even though it doesn't cause pathology there) |
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Why are UTIs more common in women?
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Distance btw colon and urethra smaller in women
->Vaginal tract can al be colonized in women |
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How is UPEC transmitted?
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Foodborne
(found in poultry) |
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What kind of infections are community acquired (and even some hospital acquired) infections? (Ascending or descending)
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ASCENDING
-Urethritis -Cystitis -Pyelonephritis -Bacteria may enter bloodstream from kidney |
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How are most hospital UTIs acquired?
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Catheters
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What kind of infections can hospital UTIs be? (ascending or descending)
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DESCENDING
->Start in the bloodstream |
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What is more common, ascending or descending infections?
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Ascending
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What kind of virulence factors does UPEC have?
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Different strains have different factors
-Adherence factors -Toxins -Nutrition -LPS -Capsule |
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What is the major virulence determinant of UPEC?
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Adhesins
-Adherence very important for UPEC |
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What is the body's major defence vs UPEC?
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Flushing action of urine
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What are UPEC's main adhesins?
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Type 1 fimbriae: adheres to bladder
Pap pili: adherence to kidney (Pap: pyelonephritis-associated pilus) |
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What is the most common virulence factor of UPEC?
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Type 1 fimbriae
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Where does type 1 fimbriae bind?
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Mannose on bladder glycoptns (ex: uroplakins)
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What invasion is type 1 fimbriae involved in?
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Uroepithelial cell invasion
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Describe Pap pili
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Heteropolymeric fibers composed of different ptn subunits
Encoded by papA-K gene operon |
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What do the pap pili recognize and bind?
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Kidney glycosphingolipids that have the Gal(1-4)Gall determinant
->This is recognized using papG adhesin |
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What type of infections is Pap pili important in?
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Ascending UTIs
Pyelonephritis |
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What effect does cranberry juice have on both tupes of UPEC adhesion? How?
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Inhibition
-> Fructose inhibits the adherence of Type 1 fimbriated E. coli to uroepithelial cells Proanthocyanidins inhibit adherence of P-fimbriate E. coli to uroepithelial cells |
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What are the UPEC toxins?
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a-hemolysin
Cytotoxic necrotising factor Sat |
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What type of bacteria produce a-hemolysin?
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Strains isolated from human ?UTI and other extraintestinal infections
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What does a-hemoysin do?
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Makes pores in eukaryotic mbs
-> Damages eukaryotic mbs |
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how do a-hemolysin -/- strains compare to regular a-hemolysin strains?
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a-hemolysin -/- are less virulent
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What does the cytotoxic necrotising factor (CNF) do?
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Modifies Rho (family that regulates actin cytoskeleton)
->Inhibits phagocytosis of PMNs (neutrophils) ->controversial role |
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Which nutrient is essential for UPEC to survive in thehost?
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Iron
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What are the most common ways for UPEc to extract iron from the host?
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-Siderophore-siderophore receptor systems (enterobactin and aerobactin)
-Heme uptake (also other ways to do this) |
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What are some other virulence factors (not adherence factors or toxins)?
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Capsule
LPS |
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What role does the bacterial capsule play in bacterial pathogenesis?
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Prevents phagocytosis by host cells
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What role does LPS play in bacterial virulence?
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Causes a host response
-> Might cause symptoms of UTI, but is necessary for bacterial clearance TLR4-/- mice are chronic, asymptomatic carriers |
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What are the hosts defenses in the bladder?
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Urine flow
Low pH in urine High [salt] in urine High [urea] in urine Lysozyme in urine Antimicrobial peptides Tamm-Horsfall ptn (THP) |
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What is the Tamm-Horsfall ptn (THP)?
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Most abundant ptn in mammals
Probably bind type I fimbriae, act as a receptor decoy |
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What infections are THP-/- mice more susceptible to?
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Infection with type 1 fimbriated UPEC strains
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What are AMPs?
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Defensins produced after pathogen exposure
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What happens to most of the uroepithelial cells that have UPEC in them?
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Get sloughed off
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How do some uroepithelial cells protect UPEC inside themselves?
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UPEC in latent phase of infection
UPEC not actively dividing Resistant to B-lactam antibiotics reservoir for recurrent infetions |
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What is the most common serotype ass't with meningitis?
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K1 E.coli
O18:K1:H7 is the most common type |
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How is E. coli transmitted around the body in meningitis infections?
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Translocated from blood to CNS
Invades brain microvascular endothelial cells in culture (cytoskeletal rearrangements) |
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What causes E. coli septiciemia?
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Intestinal perforation
Ascending UTIs E. coli lung infections in ventilator patients |
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What are the virulence factors ass't with meningitis and septicemia? What do they do?
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K1 capsule: antiphagocytic, serum resistance
LPS: causes septic shock CNF-1: required for invasion |
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What is the difference btw E. coli K1 (pathogenic) and K12 (not pathogenic)?
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22 genomic islands only in K1, not K12
These islands were +/- present in other meningitis/septicemia ass't strains |
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What happens when 9 of these islands were deleted?
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Decreased ability of K1 to cause bacterimia and meningitis
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How can ExPEC be prevented/treated?
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Antibiotics
Problem: drug resistance Prevent UTIs: careful with catheters |
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What is Crohn's disease?
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Inflammatory bowel disease (IBD)
Causes chronic intestinal inflammation |
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What is AIEC?
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Adherent/invasive E. coli
Described in Crohn's disease |
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What are the requirements to be part of AIEC?
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1) Ability to adhere to and invade intestinal epithelial cells with macropinocytosis-like rpcoess of entry, dependent on actin microfilaments and microtubule recruitment
2) Ability to survive and extensively replicate in large vacuoles within macs, without triggering host cell death 3) Ability to induce the release of large amounts of TNF-a by infected macrophages |
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How many plasmids does AIEC have? Where is it from?
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1 plasmid
Horizontal transfer from another bacteria (Salmonella?) |
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What is the closest related E. coli species to AIEC?
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avian pathogenic E. coli
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What type of secretion system does AIEC have?
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2 Type IV SS
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What other virulence factors does AIEC have?
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Sidreophores
apsule Putative invasins |
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Is AEIC a cause of Crohn's disease?
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Not sure
It's ass't with this disease but don't know if iut has a causative role in it |
