scholarly journals Novel Three-Dimensional Organoid Model for Evaluation of the Interaction of Uropathogenic Escherichia coli with Terminally Differentiated Human Urothelial Cells

2006 ◽  
Vol 74 (1) ◽  
pp. 750-757 ◽  
Author(s):  
Yarery C. Smith ◽  
Kerian K. Grande ◽  
Susan B. Rasmussen ◽  
Alison D. O'Brien

ABSTRACT Human bladder 5637 cells cultivated under microgravity conditions formed organoids that displayed characteristics of in vivo tissue-specific differentiation. Uropathogenic Escherichia coli (UPEC) strain CP9 colonized and penetrated the organoids and induced α-hemolysin-mediated exfoliation of uroepithelial cells. We propose these uro-organoids as models that simulate the interactions between UPEC and terminally differentiated human urothelium.

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e78013 ◽  
Author(s):  
Benjamin L. Duell ◽  
Alison J. Carey ◽  
Samantha J. Dando ◽  
Mark A. Schembri ◽  
Glen C. Ulett

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chunhui Miao ◽  
Mingyu Yu ◽  
Geng Pei ◽  
Zhenyi Ma ◽  
Lisong Zhang ◽  
...  

AbstractHost cells use several anti-bacterial pathways to defend against pathogens. Here, using a uropathogenic Escherichia coli (UPEC) infection model, we demonstrate that bacterial infection upregulates RhoB, which subsequently promotes intracellular bacteria clearance by inducing LC3 lipidation and autophagosome formation. RhoB binds with Beclin 1 through its residues at 118 to 140 and the Beclin 1 CCD domain, with RhoB Arg133 being the key binding residue. Binding of RhoB to Beclin 1 enhances the Hsp90-Beclin 1 interaction, preventing Beclin 1 degradation. RhoB also directly interacts with Hsp90, maintaining RhoB levels. UPEC infections increase RhoB, Beclin 1 and LC3 levels in bladder epithelium in vivo, whereas Beclin 1 and LC3 levels as well as UPEC clearance are substantially reduced in RhoB+/− and RhoB−/− mice upon infection. We conclude that when stimulated by UPEC infections, host cells promote UPEC clearance through the RhoB-Beclin 1-HSP90 complex, indicating RhoB may be a useful target when developing UPEC treatment strategies.


1986 ◽  
Vol 135 (6) ◽  
pp. 1319-1321 ◽  
Author(s):  
Walter J. Hopkins ◽  
Jean L. Jensen ◽  
David T. Uehling ◽  
Edward Balish

2019 ◽  
Vol 30 (8) ◽  
pp. 1385-1397 ◽  
Author(s):  
Tad Eichler ◽  
Kristin Bender ◽  
Matthew J. Murtha ◽  
Laura Schwartz ◽  
Jackie Metheny ◽  
...  

BackgroundEvidence suggests that antimicrobial peptides, components of the innate immune response, protect the kidneys and bladder from bacterial challenge. We previously identified ribonuclease 7 (RNase 7) as a human antimicrobial peptide that has bactericidal activity against uropathogenic Escherichia coli (UPEC). Functional studies assessing RNase 7’s contributions to urinary tract defense are limited.MethodsTo investigate RNase 7’s role in preventing urinary tract infection (UTI), we quantified urinary RNase 7 concentrations in 29 girls and adolescents with a UTI history and 29 healthy female human controls. To assess RNase 7’s antimicrobial activity in vitro in human urothelial cells, we used siRNA to silence urothelial RNase 7 production and retroviral constructs to stably overexpress RNase 7; we then evaluated UPEC’s ability to bind and invade these cells. For RNase 7 in vivo studies, we developed humanized RNase 7 transgenic mice, subjected them to experimental UTI, and enumerated UPEC burden in the urine, bladder, and kidneys.ResultsCompared with controls, study participants with a UTI history had 1.5-fold lower urinary RNase 7 concentrations. When RNase 7 was silenced in vitro, the percentage of UPEC binding or invading human urothelial cells increased; when cells overexpressed RNase 7, UPEC attachment and invasion decreased. In the transgenic mice, we detected RNase 7 expression in the kidney’s intercalated cells and bladder urothelium. RNase 7 humanized mice exhibited marked protection from UPEC.ConclusionsThese findings provide evidence that RNase 7 has a role in kidney and bladder host defense against UPEC and establish a foundation for investigating RNase 7 as a UTI prognostic marker or nonantibiotic-based therapy.


2011 ◽  
Vol 77 (19) ◽  
pp. 6852-6857 ◽  
Author(s):  
Gabriela Hidalgo ◽  
Michelle Chan ◽  
Nathalie Tufenkji

ABSTRACTIn humans, uropathogenicEscherichia coli(UPEC) is the most common etiological agent of uncomplicated urinary tract infections (UTIs). Cranberry extracts have been linked to the prevention of UTIs for over a century; however, a mechanistic understanding of the way in which cranberry derivatives prevent bacterial infection is still lacking. In this study, we used afliC-luxreporter as well as quantitative reverse transcription-PCR to demonstrate that when UPEC strain CFT073 was grown or exposed to dehydrated, crushed cranberries or to purified cranberry-derived proanthocyanidins (cPACs), expression of the flagellin gene (fliC) was inhibited. In agreement with these results, transmission electron microscopy imaging of bacteria grown in the presence of cranberry materials revealed fewer flagella than those in bacteria grown under control conditions. Furthermore, we showed that swimming and swarming motilities were hindered when bacteria were grown in the presence of the cranberry compounds. Because flagellum-mediated motility has been suggested to enable UPEC to disseminate to the upper urinary tract, we propose that inhibition of flagellum-mediated motility might be a key mechanism by which cPACs prevent UTIs. This is the first report to show that cranberry compounds inhibit UPEC motility via downregulation of thefliCgene. Further studies are required to establish whether these inhibitors play a rolein vivo.


2020 ◽  
Vol 22 ◽  
pp. 806-810
Author(s):  
Wilson Dias Segura ◽  
Haissa Pereira Ramos ◽  
Renata Ester de Faria Blanc Amorim ◽  
Ághata Cardoso da Silva Ribeiro ◽  
Edimar Cristiano Pereira ◽  
...  

2010 ◽  
Vol 190 (4) ◽  
pp. 613-621 ◽  
Author(s):  
Julio O. Ortiz ◽  
Florian Brandt ◽  
Valério R.F. Matias ◽  
Lau Sennels ◽  
Juri Rappsilber ◽  
...  

Ribosomes arranged in pairs (100S) have been related with nutritional stress response and are believed to represent a “hibernation state.” Several proteins have been identified that are associated with 100S ribosomes but their spatial organization has hitherto not been characterized. We have used cryoelectron tomography to reveal the three-dimensional configuration of 100S ribosomes isolated from starved Escherichia coli cells and we have described their mode of interaction. In situ studies with intact E. coli cells allowed us to demonstrate that 100S ribosomes do exist in vivo and represent an easily reversible state of quiescence; they readily vanish when the growth medium is replenished.


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