Effects of intravesical liposome-mediated human beta-defensin-2 gene transfection in a mouse urinary tract infection model

Expression oface(adhesin tocollagen ofEnterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism oface/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator ofaceexpression under these stress conditions. Using Northern hybridization and β-galactosidase assays of anacepromoter-lacZfusion, we found transcription ofaceto be virtually absent in agrvRdeletion mutant under the conditions that increaseaceexpression in wild-type OG1RF and in the complemented strain. Moreover, agrvRmutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control ofaceexpression andE. faecalisvirulence.

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Antibacterial immunomodulatory and antibiofilm triple effect of Salivaricin LHM against Pseudomonas aeruginosa urinary tract infection model

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2019.05.181 ◽

2019 ◽

Vol 134 ◽

pp. 1132-1144 ◽

Cited By ~ 3

Author(s):

Likaa Hamied Mahdi ◽

Hussein Satar Jabbar ◽

Ibtesam Ghadban Auda

Keyword(s):

Pseudomonas Aeruginosa ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Infection Model

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Triclosan Loaded Ureteral Stents Decrease Proteus Mirabilis 296 Infection in a Rabbit Urinary Tract Infection Model

The Journal of Urology ◽

10.1016/s0022-5347(06)00252-7 ◽

2006 ◽

Vol 175 (6) ◽

pp. 2331-2335 ◽

Cited By ~ 56

Author(s):

Peter A. Cadieux ◽

Ben H. Chew ◽

Bodo E. Knudsen ◽

Kathy DeJong ◽

Elaine Rowe ◽

...

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Proteus Mirabilis ◽

Infection Model ◽

Ureteral Stents

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Efficacy of Ceftobiprole Medocaril against Enterococcus faecalis in a Murine Urinary Tract Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06102-11 ◽

2012 ◽

Vol 56 (6) ◽

pp. 3457-3460 ◽

Cited By ~ 6

Author(s):

Kavindra V. Singh ◽

Barbara E. Murray

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Enterococcus Faecalis ◽

Infection Model ◽

Content Type ◽

The Stability

ABSTRACTWe evaluated ceftobiprole against the well-characterizedEnterococcus faecalisstrain OG1RF (with and without the β-lactamase [Bla] plasmid pBEM10) in a murine urinary tract infection (UTI) model. Ceftobiprole was equally effective for Bla+and Bla−OG1 strains, while ampicillin was moderately to markedly (depending on the inoculum) less effective against Bla+than Bla−OG1 strains. These data illustrate anin vivoeffect on ampicillin of Bla production byE. faecalisand the stability and efficacy of ceftobiprole in experimental UTI.

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Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder

10.1101/2020.04.18.048074 ◽

2020 ◽

Author(s):

Livia Lacerda Mariano ◽

Matthieu Rousseau ◽

Hugo Varet ◽

Rachel Legendre ◽

Rebecca Gentek ◽

...

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Infection Model ◽

Bacterial Clearance ◽

Resident Macrophage ◽

Inflammatory Profile ◽

Common Infection ◽

Macrophage Subsets

SummaryResident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in the muscle and MacL in the lamina propria, with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the MacL subset died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Depletion of these altered macrophages resulted in the induction of a type 1 biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their response to an exceedingly common infection in a largely overlooked organ, the bladder.

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DamX Controls Reversible Cell Morphology Switching in UropathogenicEscherichia coli

mBio ◽

10.1128/mbio.00642-16 ◽

2016 ◽

Vol 7 (4) ◽

Cited By ~ 26

Author(s):

Surabhi Khandige ◽

Cecilie Antoinette Asferg ◽

Karina Juhl Rasmussen ◽

Martin Jakob Larsen ◽

Martin Overgaard ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract Infection ◽

Cell Division ◽

Urinary Tract ◽

Tract Infection ◽

Cell Morphology ◽

Pathogenic Bacteria ◽

Infection Model ◽

Tract Infections

ABSTRACTThe ability to change cell morphology is an advantageous characteristic adopted by multiple pathogenic bacteria in order to evade host immune detection and assault during infection. UropathogenicEscherichia coli(UPEC) exhibits such cellular dynamics and has been shown to transition through a series of distinct morphological phenotypes during a urinary tract infection. Here, we report the first systematic spatio-temporal gene expression analysis of the UPEC transition through these phenotypes by using a flow chamber-basedin vitroinfection model that simulates conditions in the bladder. This analysis revealed a novel association between the cell division genedamXand reversible UPEC filamentation. We demonstrate a lack of reversible bacterial filamentation in adamXdeletion mutantin vitroand absence of a filamentous response by this mutant in a murine model of cystitis. While deletion ofdamXabrogated UPEC filamentation and secondary surface colonization in tissue culture and in mouse infections, transient overexpression ofdamXresulted in reversible UPEC filamentation. In this study, we identify a hitherto-unknowndamX-mediated mechanism underlying UPEC morphotypical switching. Murine infection studies showed that DamX is essential for establishment of a robust urinary tract infection, thus emphasizing its role as a mediator of virulence. Our study demonstrates the value of anin vitromethodology, in which uroepithelium infection is closely simulated, when undertaking targeted investigations that are challenging to perform in animal infection models.IMPORTANCEUrinary tract infections (UTIs) are most often caused by uropathogenicEscherichia coli(UPEC) and account for a considerable health care burden. UPEC exhibits a dynamic lifestyle in the course of infection, in which the bacterium transiently adopts alternative morphologies ranging from rod shaped to coccoid and filamentous, rendering it better at immune evasion and host epithelium adhesion. This penchant for morphotype switching might in large measure account for UPEC’s success as a pathogen. In aiming to uncover genes underlying the phenomenon of UPEC morphotype switching, this study identifiesdamX, a cell division gene, as a mediator of reversible filamentation during UTI. DamX-mediated filamentation represents an additional pathway for bacterial cell shape control, an alternative to SulA-mediated FtsZ sequestration duringE. coliuropathogenesis, and hence represents a potential target for combating UTI.

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Ciprofloxacin Pharmacokinetics/Pharmacodynamics against Susceptible and Low-Level Resistant Escherichia coli Isolates in an Experimental Ascending Urinary Tract Infection Model in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01804-20 ◽

2020 ◽

Vol 65 (1) ◽

pp. e01804-20

Author(s):

Lotte Jakobsen ◽

Carina Vingsbro Lundberg ◽

Niels Frimodt-Møller

Keyword(s):

Escherichia Coli ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Infection Model ◽

Bladder Tissue ◽

Content Type ◽

E Coli ◽

Low Level ◽

Level Resistance

ABSTRACTThe mouse ascending urinary tract infection model was used to study the pharmacokinetic/pharmacodynamic (PKPD) relationships of the effect of ciprofloxacin in subcutaneous treatment for 3 days with varying doses and dosing intervals against a susceptible Escherichia coli strain (MIC, 0.032 mg/liter). Further, a humanized dose of ciprofloxacin was administered for 3 days against three E. coli strains with low-level resistance, i.e., MICs of 0.06, 0.25, and 1 mg/liter, respectively. Against the susceptible isolate, ciprofloxacin was highly effective in clearing the urine with daily doses from 10 mg/kg, but the dosing regimen had to be divided into at least two doses for optimal effect. Ciprofloxacin could not clear the urine or kidneys for the low-level-resistant strains. PKPD correlations with all strains combined showed that for the AUC24/MIC there was a slightly higher correlation with effect in urine and kidneys (R2, 0.71 and 0.69, respectively) than the %T>MIC (R2, 0.41 and 0.61, respectively). Equal correlations for the two PKPD indices were found for reduction of colony counts (CFU) in the bladder tissue, but not even the highest dose of 28 mg/kg × 6 could clear the bladder tissue. In conclusion, ciprofloxacin is highly effective in clearing the urine and kidney tissue for fully susceptible E. coli, while even low-level resistance in E. coli obscures this effect. While the effect of ciprofloxacin is mostly AUC/MIC driven against E. coli infection in the urinary tract, the effect in urine depends on the presence of ciprofloxacin in the urine during most of a 24-h period.

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