scholarly journals Uropathogenic E. coli induces DNA damage in the bladder

2020 ◽  
Author(s):  
Camille V. Chagneau ◽  
Clémence Massip ◽  
Nadège Bossuet-Greif ◽  
Christophe Fremez ◽  
Jean-Paul Motta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Dna Damage ◽  
Bladder Cancer ◽  
Urinary Tract ◽  
Bacterial Communities ◽  
E Coli ◽  
Bladder Cells ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

AbstractUrinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of a metabolite released during the synthesis of colibactin, a bacterial genotoxin, in 50 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells. This bacterial genotoxin, which is increasingly suspected to promote colorectal cancer, should also be scrutinised in the context of bladder cancer.

scholarly journals Uropathogenic E. coli induces DNA damage in the bladder

2021 ◽  
Vol 17 (2) ◽  
pp. e1009310
Author(s):  
Camille V. Chagneau ◽  
Clémence Massip ◽  
Nadège Bossuet-Greif ◽  
Christophe Fremez ◽  
Jean-Paul Motta ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Bacterial Communities ◽  
Cleavage Product ◽  
E Coli ◽  
Bladder Cells ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells.

scholarly journals Involvement of biofilm-like in tracellular bacterial communities of uropathogenic Escherichia coli in pathogenesis of urinary tract infections – a mini review

2013 ◽  
Vol 26 (3) ◽  
pp. 321-325
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Bacterial Communities ◽  
Uropathogenic Escherichia Coli ◽  
E Coli ◽  
Etiologic Agents ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

This paper presents a precisely defined question about the role of the biofilm-like intracellular bacterial communities in pathogenesis of the urinary tract infections. According to the recent literature, uropathogenic Escherichia coli is one of the leading etiologic agents of the urinary tract infections. Although E. coli is regarded as an extracellular pathogen, some experiments have revealed a multi-step infection cycle, which involves adhesion, invasion, proliferation within invaded urothelial cell in the form of biofilm-like intracellular bacterial communities and dispersal, leading to infection of next neighbouring cells. Therefore, the prevention and treatment of the urinary tract infections must include intracellular stage of infection.

scholarly journals Distinct Morphological Fates of Uropathogenic Escherichia coli Intracellular Bacterial Communities: Dependency on Urine Composition and pH

2020 ◽  
Vol 88 (9) ◽  
Author(s):  
Gregory Iosifidis ◽  
Iain G. Duggin
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Epithelial Cells ◽  
Human Urine ◽  
Bacterial Communities ◽  
Acute Infection ◽  
Infection Cycle ◽  
Bladder Cells ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections. These bacteria undertake a multistage infection cycle involving invasion of and proliferation within urinary tract epithelial cells, leading to the rupture of the host cell and dispersal of the bacteria, some of which have a highly filamentous morphology. Here, we established a microfluidics-based model of UPEC infection of immortalized human bladder epithelial cells that recapitulates the main stages of bacterial morphological changes during the acute infection cycle in vivo and allows the development and fate of individual cells to be monitored in real time by fluorescence microscopy. The UPEC-infected bladder cells remained alive and mobile in nonconfluent monolayers during the development of intracellular bacterial communities (IBCs). Switching from a flow of growth medium to human urine resulted in immobilization of both uninfected and infected bladder cells. Some IBCs continued to develop and then released many highly filamentous bacteria via an extrusion-like process, whereas other IBCs showed strong UPEC proliferation, and yet no filamentation was detected. The filamentation response was dependent on the weak acidity of human urine and required component(s) in a low molecular-mass (<3,000 Da) fraction from a mildly dehydrated donor. The developmental fate for bacteria therefore appears to be controlled by multiple factors that act at the level of the whole IBC, suggesting that variable local environments or stochastic differentiation pathways influence IBC developmental fates during infection.

scholarly journals Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection

2001 ◽  
Vol 69 (7) ◽  
pp. 4572-4579 ◽  
Author(s):  
Matthew A. Mulvey ◽  
Joel D. Schilling ◽  
Scott J. Hultgren
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Epithelial Cells ◽  
Urinary Tract Infections ◽  
Bacterial Attachment ◽  
Bacterial Invasion ◽  
E Coli ◽  
Bladder Cells ◽  
Tract Infections

ABSTRACT The vast majority of urinary tract infections are caused by strains of uropathogenic Escherichia coli that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular E. coli termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed.

scholarly journals Dynamic persistence of intracellular bacterial communities of uropathogenic Escherichia coli in a human bladder-chip model of urinary tract infections

2021 ◽  
Author(s):  
Kunal Sharma ◽  
Neeraj Dhar ◽  
Vivek V. Thacker ◽  
Thomas Simonet ◽  
François Signorino-Gelo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Epithelial Cells ◽  
Urinary Tract Infections ◽  
Bacterial Communities ◽  
Antibiotic Administration ◽  
Human Bladder ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

AbstractUropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infections and is a major cause for antibiotic prescriptions. Previous studies have shown that infection of terminally differentiated urinary bladder cells leads to the formation of intracellular bacterial communities (IBCs). However, the precise role of IBCs in recurrence of infection and antibiotic persistence, is not completely understood in part because the in situ dynamic responses of bacteria within these structures to antibiotic stress is difficult to assess in animal models. Here, we develop and characterize a human bladder-chip model of UPEC infection wherein superficial bladder epithelial cells and bladder microvascular endothelial cells are co-cultured under flow in urine and nutritive media respectively, and the mechanics of bladder filling and voiding cycles mimicked by application and release of linear strain. Time-lapse microscopy showed that infection of epithelial cells under shear stress in diluted urine led to the rapid recruitment and diapedesis of neutrophils across the endothelial-epithelial barrier and the formation of neutrophil swarms and neutrophil extracellular traps. Subsequently, two cycles of antibiotic administration interspersed with recovery periods revealed both non-growing and rapidly proliferating IBCs. Multiple stages of IBC formation captured on-chip with single-cell resolution revealed that that bacterial killing within IBCs was substantially delayed, outcomes such as shedding of bacteria and exfoliation are not mutually exclusive and rapidly reseeded the infection, and in rare instances bacterial growth in IBCs continued for the entire period of antibiotic administration. These new insights into the early stages of pathogenesis revisit the role of IBCs as harbours of persistent bacterial populations, with significant consequences for non-compliance with antibiotic regimens.

scholarly journals Metabolic Requirements ofEscherichia coliin Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Matt S. Conover ◽  
Maria Hadjifrangiskou ◽  
Joseph J. Palermo ◽  
Michael E. Hibbing ◽  
Karen W. Dodson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Urinary Tract ◽  
Bacterial Communities ◽  
Type Strain ◽  
Wild Type Strain ◽  
Wild Type ◽  
Bladder Cells ◽  
Tract Infections ◽  
Intracellular Bacterial Communities

ABSTRACTUropathogenicEscherichia coli(UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly,lacZwas highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZstrain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, agalKmutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated geneyeaRrevealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies.IMPORTANCEUrinary tract infections (UTIs) are one of the most common bacterial infections, impacting mostly women. Every year, millions of UTIs occur in the U.S. with most being caused by uropathogenicE. coli(UPEC). During a UTI, UPEC invade bladder cells and form an intracellular bacterial community (IBC) that allows for the bacteria to replicate protected from the host immune response. In this study, we investigated genes that are expressed by UPEC within the IBC and determined how they contribute to the formation of this specialized community. Our findings suggest that galactose is important for UPEC growth in the IBC. Additionally, we found that a gene involved in oxidative stress is also important in the regulation of a key factor needed for UPEC invasion of bladder cells. These results may open the door for the development of treatments to diminish UTI frequency and/or severity.

Aqueous Root Extract from Ononis spinosa Exerts Anti-adhesive Activity against Uropathogenic Escherichia coli

Planta Medica ◽  
2020 ◽  
Vol 86 (04) ◽  
pp. 247-254 ◽  
Author(s):  
Melanie Deipenbrock ◽  
Jandirk Sendker ◽  
Andreas Hensel
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Cell Viability ◽  
Urinary Tract Infections ◽  
Bacterial Adhesion ◽  
Uropathogenic Escherichia Coli ◽  
E Coli ◽  
T24 Cells ◽  
Bladder Cells ◽  
Tract Infections

AbstractExtracts from Ononis spinosa are traditionally used for urinary tract infections due to diuretic and anti-inflammatory activity. A potential influence on the virulence of uropathogenic Escherichia coli has not been investigated until now. The following study aimed to investigate the influence of an aqueous O. spinosa extract on uropathogenic E. coli and uropathogenic E. coli host cell interaction. A hot water extract from the roots of O. spinosa (O. spinosa extract) was characterized by LC-qTOF-MS. The influence of O. spinosa extract on the proliferation of uropathogenic E. coli UTI89 and on cell viability against human T24 bladder cells was investigated. Anti-adhesive activity of O. spinosa extract was assessed by flow cytometry, evaluating the adhesion of fluorescent-labelled UTI89 to T24 bladder cells. Internalization of uropathogenic E. coli into T24 cells was monitored by an invasion assay. O. spinosa extract was characterized by the presence of isoflavones, isoflavanones, licoagrosides, pterocarpans, tartaric acid derivatives, and saponines. O. spinosa extract had no influence on the proliferation of uropathogenic E. coli (125 – 1000 µg/mL) and did not influence the cell viability of T24 cells. Bacterial adhesion to T24 cells was significantly (p > 0.001) inhibited by O. spinosa extract in a concentration-dependent manner (125 – 1000 µg/mL) during coincubation. Preincubation of uropathogenic E. coli or T24 cells with O. spinosa extract reduced bacterial adhesion, but to a lower extent than during coincubation. Consequently, the reduced bacterial adhesion also leads to a reduced internalization of uropathogenic E. coli uropathogenic E. coli into the host cell. O. spinosa extract does not interact with FimH-mediated uropathogenic E. coli adhesion to host cells. From these data, the traditional use of O. spinosa extracts for urinary tract infections seems to be rationalized.

scholarly journals Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans

2021 ◽  
Vol 9 (2) ◽  
pp. 310
Author(s):  
Masayuki Hashimoto ◽  
Yi-Fen Ma ◽  
Sin-Tian Wang ◽  
Chang-Shi Chen ◽  
Ching-Hao Teng
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Caenorhabditis Elegans ◽  
Large Scale ◽  
Iron Acquisition ◽  
Infection Model ◽  
High Throughput Analysis ◽  
E Coli ◽  
C Elegans ◽  
Tract Infections

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

scholarly journals Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1348
Author(s):  
Lívia Slobodníková ◽  
Barbora Markusková ◽  
Michal Kajsík ◽  
Michal Andrezál ◽  
Marek Straka ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Therapeutic Potential ◽  
Medical Intervention ◽  
Uropathogenic Escherichia Coli ◽  
E Coli ◽  
Phage Cocktail ◽  
Causative Agents ◽  
Tract Infections

Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.

Viability and survival capability of quinolone-resistant uropathogenic Escherichia coli

2010 ◽  
Vol 5 (6) ◽  
pp. 827-830
Author(s):  
Georgi Slavchev ◽  
Nadya Markova
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Expression System ◽  
Antibiotic Sensitivity ◽  
Uropathogenic Escherichia Coli ◽  
Resistant Bacteria ◽  
E Coli ◽  
Serum Bactericidal Assay ◽  
Tract Infections ◽  
Macrophage Killing

AbstractUropathogenic strains of E. coli isolated from urine of patients with urinary tract infections were tested for antibiotic sensitivity using bio-Merieux kits and ATB-UR 5 expression system. The virulence of strains was evaluated by serum bactericidal assay, macrophage “killing” and bacterial adhesive tests. Survival capability of strains was assessed under starvation in saline. The results showed that quinolone-resistant uropathogenic strains of E. coli exhibit significantly reduced adhesive potential but relatively high resistance to serum and macrophage bactericidity. In contrast to laboratory strains, the quinolone-resistant uropathogenic clinical isolate demonstrated increased viability during starvation in saline. Our study suggests that quinolone-resistant uropathogenic strains are highly adaptable clones of E. coli, which can exhibit compensatory viability potential under unfavorable conditions. The clinical occurrence of such phenotypes is likely to contribute to the survival, persistence and spread strategy of resistant bacteria.

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