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Contributions of select extracellula...
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Wright, Kelly Jeanne.
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Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo./
Author:
Wright, Kelly Jeanne.
Description:
240 p.
Notes:
Adviser: Scott J. Hultgren.
Contained By:
Dissertation Abstracts International67-10B.
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3238686
ISBN:
9780542926785
Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo.
Wright, Kelly Jeanne.
Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo.
- 240 p.
Adviser: Scott J. Hultgren.
Thesis (Ph.D.)--Washington University in St. Louis, 2006.
Uropathogenic Escherichia coli (UPEC) is the predominant causative agent of urinary tract infections (UTI). Superficial umbrella cells lining the bladder lumen present the first barrier to invading organisms. UPEC have evolved many defenses to overcome innate host defense mechanisms, including adherence to epithelial cell barriers. Little is known regarding factors other than type 1 pili which contribute to adherence and virulence. Type 1 pili, the preeminent cystitis virulence determinant, bind bladder epithelium thereby initiating rapid invasion to avoid host clearance mechanisms. Invaded bacteria may replicate intracellularly to form intracellular bacterial communities (IBCs), a protected niche with biofilm-like properties. To further elucidate mechanisms UPEC utilize to establish infection and persist within the urinary tract, we examined the contribution of extracellular organelles to uropathogenesis focusing on the IBC developmental cascade.
ISBN: 9780542926785Subjects--Topical Terms:
1017686
Biology, Cell.
Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo.
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Contributions of select extracellular uropathogenic Escherichia coli organelles during acute and persistent urinary tract infection in vivo.
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240 p.
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Adviser: Scott J. Hultgren.
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Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5546.
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Thesis (Ph.D.)--Washington University in St. Louis, 2006.
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Uropathogenic Escherichia coli (UPEC) is the predominant causative agent of urinary tract infections (UTI). Superficial umbrella cells lining the bladder lumen present the first barrier to invading organisms. UPEC have evolved many defenses to overcome innate host defense mechanisms, including adherence to epithelial cell barriers. Little is known regarding factors other than type 1 pili which contribute to adherence and virulence. Type 1 pili, the preeminent cystitis virulence determinant, bind bladder epithelium thereby initiating rapid invasion to avoid host clearance mechanisms. Invaded bacteria may replicate intracellularly to form intracellular bacterial communities (IBCs), a protected niche with biofilm-like properties. To further elucidate mechanisms UPEC utilize to establish infection and persist within the urinary tract, we examined the contribution of extracellular organelles to uropathogenesis focusing on the IBC developmental cascade.
520
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We characterized flagella as dispensable throughout IBC formation and acute infection but discovered this organelle to confer a fitness advantage during persistent cystitis and pyelonephritis. Moreover, we performed the first in vivo assessment of flagellar gene activity. Unlike in vitro motility modeling, the hierarchal regulatory cascade appeared incomplete during acute cystitis, a result consistent with acute infection studies. Assessment of S pili during experimental UTI was performed following discovery of a novel regulatory link between the fim and sfa operons in cystitis strain, UTI89. S pili were not essential during acute or persistent UTI however S pili imparted a strain-dependent kidney tropism and may mediate neutrophil influx into the bladder. Most notable of our discoveries was dependence of IBC initiation and maturation on type 1 pili. Construction of a novel conditional fim expression strain allowed in vivo invasion followed by fim repression. Despite intact invasion capabilities, absence of intracellular type 1 pili significantly attenuated IBC formation and ultrastructure. Non-piliated, intracellular bacteria were either cleared or distributed diffusely throughout the cytoplasm and unable to undergo the rod to coccoid morphological transition characteristic of bacteria within maturing IBCs. Together these studies greatly improve our understanding of extracellular organelles utilized by UPEC during UTI and allow refinement of targeted therapeutic design in developing novel UTI treatments which account for both intracellular and extracellular bacterial reservoirs.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3238686
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