Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections

O’Brien, Valerie P.; Hannan, Thomas J.; Nielsen, Hailyn V.; Hultgren, Scott J.

doi:10.1128/microbiolspec.uti-0013-2012

Cited by 110 publications

(103 citation statements)

References 419 publications

(390 reference statements)

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“…Urinary tract infections (UTIs) are among the most common bacterial infections, affecting 150 million people worldwide each year [1–3]. Although both men and women may become infected, UTIs are traditionally thought of as a disease of women, among whom 50% will be affected across their lifespan [2].…”

Section: A Pervasive and Persistent Problemmentioning

confidence: 99%

“…In traditional mouse models, severe kidney infection (including renal abscess formation) is uncommon, hampering the study of this entity. Attenuation in mouse kidney infections has been observed with UPEC mutants lacking specific virulence factors, such as type 1 pili, P pili, flagella, α-hemolysin , and cytotoxic necrotizing factor 1 (CNF1) [3, 9]. Further, genetics appear to play a role in host susceptibility to acute pyelonephritis.…”

Section: Molecular Pathogenesis Of Utimentioning

confidence: 99%

“…Multiple groups have worked to identify specific UPEC factors for potential use as vaccine antigens. Candidate antigens include the FimH adhesin, siderophores such as yersiniabactin [87], and other immunodominant proteins identified in mouse models [88, 89] (reviewed in [3, 90]). Two important considerations may hinder the effectiveness of vaccine candidates against UTI.…”

Section: Next-generation Therapeuticsmentioning

confidence: 99%

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Urinary Tract Infection: Pathogenesis and Outlook

McLellan

Hunstad

2016

Trends in Molecular Medicine

265

206

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The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities.

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Section: A Pervasive and Persistent Problemmentioning

confidence: 99%

Section: Molecular Pathogenesis Of Utimentioning

confidence: 99%

Section: Next-generation Therapeuticsmentioning

confidence: 99%

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Urinary Tract Infection: Pathogenesis and Outlook

McLellan

Hunstad

2016

Trends in Molecular Medicine

265

206

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“…Uropathogenic Escherichia coli (UPEC) utilize a variety of virulence factors such as surface structural components, like lipopolysaccharide, capsule, flagella, pili, outer membrane proteins, as well as secreted toxins and siderophore. Consequently, these mechanisms are double edged weapon as they play an important role in UTI pathogenesis furthermore; they are attractive candidates for the development of new drugs and vaccines (Werneburg et al, 2015& O'Brien et al, 2016.…”

Section: Issn: 2319-7706 Volume 7 Number 02 (2018)mentioning

confidence: 99%

Microbiological Profile of Urinary Tract Infections with special Reference to Antibiotic Susceptibility Pattern of Escherichia coli Isolates

Hegazy¹,

Din²,

Amin³

et al. 2018

Int.J.Curr.Microbiol.App.Sci

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confidence: 99%

Correlative Light, Electron, and Ion Microscopy for the Study of Urinary Tract Infection Pathogenesis

2017

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Urinary tract infections (UTI) are common and costly infectious diseases, afflicting more than half of all women [1] and contributing to increasing medical costs and the spread of multi-drug resistant bacteria [2,3]. Bladder microscopy has been an essential tool for elucidating the pathogenesis of UTI caused by Escherichia coli [4][5][6]. Indeed, the discovery that E. coli forms intracellular bacterial communities (IBCs) within the bladder epithelium came from histology, fluorescence microscopy, scanning electron microscopy (SEM), and freeze fracture analysis of infected bladders [4,7]. However, many aspects of host-pathogen interactions in UTI remain poorly understood, including: the behavior of E. coli within the IBC; the impact of host genetic background on susceptibility to infection; the causes and consequences of epithelial cell death and exfoliation in response to infection; the pathogenesis of lessstudied uropathogens, especially Gram-positive bacteria; and the changes to the bladder epithelium imparted by urinary catheterization. Although much research has been done in previous years, improved microscopy methods are needed in order to help answer these questions.Notably, we have pioneered correlative light and electron microscopy on whole bladders infected with GFP-overexpressing E. coli to investigate IBC ultrastructure and assess the bacterial components necessary for functional IBCs. In order to correlate these structures across multiple microscopy modalities, three important conditions had to be met in order to minimize preparation-related artifacts and a to precisely correlate sample positions across multiple microscopes: 1) Since the targeting of IBCs required fluorescence microscopy, additional stains used for fiducial marking of features across both microscopes such as cell borders or nuclei needed to reach their targets without the use of permeabilizing agents or detergents, as these would disrupt the epithelial surface for SEM/ion beam analysis. 2) All fluorescence imaging had to be done with the samples still in their hydrated state to maintain fluorescence, while SEM imaging had to be performed with dehydrated samples under high vacuum conditions. 3) The samples needed to be mounted to a device with static features that could be visualized on both microscopes for Cartesian coordinate mapping and such that both the device and the tissue could withstand dehydration and avoid any forms of distortion or shrinkage. To meet all of these conditions, we created a single direction processing pipeline that started with samples being adhered to indium tin oxide coated coverslips that featured metal-deposited fiducial marks on three corners for position tracking [8]. These bladders were then sandwiched between a second coverslip and a spacer and analyzed on a laser scanning confocal microscope. The samples were then loaded into a critical point drier without any secondary staining or dehydration steps and subsequently coated with 6 nm of iridium. Following coating, the coverslips were then loaded into a...

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Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections

Cited by 110 publications

References 419 publications

Urinary Tract Infection: Pathogenesis and Outlook

Urinary Tract Infection: Pathogenesis and Outlook

Microbiological Profile of Urinary Tract Infections with special Reference to Antibiotic Susceptibility Pattern of Escherichia coli Isolates

Correlative Light, Electron, and Ion Microscopy for the Study of Urinary Tract Infection Pathogenesis

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