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Pathogens
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Molecular and Cellular Aspects of Urinary Tract Infection
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Molecular and Cellular Aspects of Urinary Tract Infection

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 21211

Special Issue Editor

Dr. Kylie Mansfield

E-Mail Website
Guest Editor
School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia
Interests: overactive bladder; infection and inflammation; purinergic signalling; medical education

Special Issue Information

Dear Colleagues,

Urinary tract infections are experienced by approximately 80% of women during their lifetime. Approximately 30% of these women will experience recurrent infections within 6 months, despite receiving antibiotic therapy. Uropathogens have developed virulence mechanisms that allow them to evade the host immune response and invade the lining of the urinary tract. Urinary tract infections are associated with debilitating symptoms of urgency, frequency, and pain, and recurrent infections are believed to be associated with the development of bladder dysfunctions, including conditions such as overactive bladder.

The focus of this Special Issue is on the properties of uropathogens that lead to recurrent infections, how interactions between the urinary microbiome and uropathogen prevent infection, and how uropathogens influence the immune and sensory functions of the urinary tract. A second focus is on how our understanding of these factors can be used to develop therapies that prevent recurrent infections. This Special Issue will aim to provide a comprehensive review of the molecular and cellular aspects that contribute to recurrent urinary tract infections and of the potential therapeutic approaches available to prevent recurrent urinary tract infections. 

Dr. Kylie Mansfield
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uropathogen
  • microbiome
  • recurrent urinary tract infection
  • invasion
  • urothelium
  • afferent nerve sensations
  • prevention
  • non-antibiotic therapy

Published Papers (6 papers)

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Research

Jump to: Review, Other

22 pages, 10192 KiB  
Article
Differential Contribution of Hydrogen Metabolism to Proteus mirabilis Fitness during Single-Species and Polymicrobial Catheterized Urinary Tract Infection
by Aimee L. Brauer, Brian S. Learman and Chelsie E. Armbruster
Pathogens 2023, 12(12), 1377; https://doi.org/10.3390/pathogens12121377 - 22 Nov 2023
Viewed by 965
Abstract
Proteus mirabilis is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for P. mirabilis CAUTI: a Hyb-type Group 1c H [...] Read more.
Proteus mirabilis is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for P. mirabilis CAUTI: a Hyb-type Group 1c H2-uptake hydrogenase and a Hyf-type Group 4a H2-producing hydrogenase. In this study, we disrupted one gene of each system (hyfE and hybC) and also generated a double mutant to examine the contribution of flexible H2 metabolism to P. mirabilis growth and fitness in vitro and during experimental CAUTI. Since P. mirabilis is typically present as part of a polymicrobial community in the urinary tract, we also examined the impact of two common co-colonization partners, Providencia stuartii and Enterococcus faecalis, on the expression and contribution of each hydrogenase to fitness. Our data demonstrate that neither system alone is critical for P. mirabilis growth in vitro or fitness during experimental CAUTI. However, perturbation of flexible H2 metabolism in the ∆hybC∆hyfE double mutant decreased P. mirabilis fitness in vitro and during infection. The Hyf system alone contributed to the generation of proton motive force and swarming motility, but only during anaerobic conditions. Unexpectedly, both systems contributed to benzyl viologen reduction in TYET medium, and disruption of either system increased expression of the other. We further demonstrate that polymicrobial interactions with P. stuartii and E. faecalis alter the expression of Hyb and Hyf in vitro as well as the contribution of each system to P. mirabilis fitness during CAUTI. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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12 pages, 2424 KiB  
Article
Role of Bacterial Surface Components in the Pathogenicity of Proteus mirabilis in a Murine Model of Catheter-Associated Urinary Tract Infection
by Roman Herout, Sara Khoddami, Igor Moskalev, Alina Reicherz, Ben H. Chew, Chelsie E. Armbruster and Dirk Lange
Pathogens 2023, 12(4), 509; https://doi.org/10.3390/pathogens12040509 - 24 Mar 2023
Cited by 2 | Viewed by 1893
Abstract
Proteus mirabilis (PM) is a Gram-negative, rod-shaped bacterium that causes catheter-associated urinary tract infections (CAUTIs). The specific roles of bacterial surface components (BSCs) in PM pathogenicity and CAUTIs remain unknown. To address this knowledge gap, we utilized relevant in vitro adhesion/invasion [...] Read more.
Proteus mirabilis (PM) is a Gram-negative, rod-shaped bacterium that causes catheter-associated urinary tract infections (CAUTIs). The specific roles of bacterial surface components (BSCs) in PM pathogenicity and CAUTIs remain unknown. To address this knowledge gap, we utilized relevant in vitro adhesion/invasion models and a well-established murine model of CAUTI to assess the ability of wildtype (WT) and seven mutant strains (MSs) of PM with deficiencies in various genes encoding BSCs to undergo the infectious process (including adhesion to catheters) in both model systems. Overall, MSs adhesion to catheters and the different cell types tested was significantly reduced compared to WT, while no invasion of cells was evident at 24 h. In vivo, WT showed a greater number of planktonic (urine) bacteria, bacteria adherent to catheters, and bacteria adherent to/invading bladder tissue when compared to the MSs. Bacterial counts in urine for PMI3191 and waaE mutants were lower than that for WT and other MSs. The complementation of mutated BSC genes resulting in the biggest defects restored the invasion phenotype both in vitro and in vivo. BSCs play a critical role at various steps in the pathogenicity of PM including adhesion to indwelling medical devices and adhesion/invasion of urinary tissue in vivo. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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11 pages, 1380 KiB  
Article
Virulence Mechanisms of Common Uropathogens and Their Intracellular Localisation within Urothelial Cells
by Samantha Ognenovska, Chinmoy Mukerjee, Martina Sanderson-Smith, Kate H. Moore and Kylie J. Mansfield
Pathogens 2022, 11(8), 926; https://doi.org/10.3390/pathogens11080926 - 17 Aug 2022
Cited by 5 | Viewed by 1302
Abstract
A recurrent urinary tract infection (UTI) is a common debilitating condition whereby uropathogens are able to survive within the urinary tract. In this study, we aimed to determine if the common uropathogens Escherichia coli, Enterococcus faecalis, and Group B Streptococcus possessed [...] Read more.
A recurrent urinary tract infection (UTI) is a common debilitating condition whereby uropathogens are able to survive within the urinary tract. In this study, we aimed to determine if the common uropathogens Escherichia coli, Enterococcus faecalis, and Group B Streptococcus possessed virulence mechanisms that enable the invasion of urothelial cells. Urothelial cells were isolated from women with detrusor overactivity and recurrent UTIs; the intracellular localisation of the uropathogens was determined by confocal microscopy. Uropathogens were also isolated from women with acute UTIs and their intracellular localisation and virulence mechanisms were examined (yeast agglutination, biofilm formation, and haemolysis). Fluorescent staining and imaging of urothelial cells isolated from women with refractory detrusor overactivity and recurrent UTIs demonstrated that all three uropathogens were capable of intracellular colonisation. Similarly, the bacterial isolates from women with acute UTIs were also seen to intracellularly localise using an in vitro model. All Enterococcus and Streptococcus isolates possessed a haemolytic capacity and displayed a strong biofilm formation whilst yeast cell agglutination was unique to Escherichia coli. The expression of virulence mechanisms by these uropathogenic species was observed to correlate with successful urothelial cell invasion. Invasion into the bladder urothelium was seen to be a common characteristic of uropathogens, suggesting that bacterial reservoirs within the bladder contribute to the incidence of recurrent UTIs. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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Review

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13 pages, 792 KiB  
Review
Effective Treatments of UTI—Is Intravesical Therapy the Future?
by Chris J. Morris, Jennifer L. Rohn, Scott Glickman and Kylie J. Mansfield
Pathogens 2023, 12(3), 417; https://doi.org/10.3390/pathogens12030417 - 06 Mar 2023
Cited by 2 | Viewed by 2322
Abstract
Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is [...] Read more.
Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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14 pages, 709 KiB  
Review
The Continuum of Microbial Ecosystems along the Female Reproductive Tract: Implications for Health and Fertility
by Claudia Nakama, Brice Thompson, Cory Szybala, Andrea McBeth, Piper Dobner and Heather Zwickey
Pathogens 2022, 11(11), 1244; https://doi.org/10.3390/pathogens11111244 - 27 Oct 2022
Cited by 3 | Viewed by 3801
Abstract
The microbial ecosystem of the female urogenital tract is composed of many niche microenvironments across multiple organ systems in the urinary and reproductive tract. It is complex and contains a variety of bacteria, archaea, viruses, yeast, and protozoa—Many of which are still unidentified [...] Read more.
The microbial ecosystem of the female urogenital tract is composed of many niche microenvironments across multiple organ systems in the urinary and reproductive tract. It is complex and contains a variety of bacteria, archaea, viruses, yeast, and protozoa—Many of which are still unidentified or whose functionality is unknown. Unlike the gut microbiome, whose composition is relatively stable in the absence of external perturbations, the urogenital microbiome is constantly shifting in response to biological cycles such as hormonal fluctuations during menstruation. Microbial composition differs between women but the dominance of some microbial families, such as Lactobacillaceae and other lactic acid-producing bacteria, are shared. Research suggests that it is difficult to define a universal healthy urogenital microbiome and consequently map a path to recovery from disease due to dysbiosis. Due to its temporal shifts, the female urogenital microbiome offers a unique opportunity to examine the biological mechanisms that work to restore a microbiome to its baseline. Common functional disorders in women’s health are often difficult to diagnose and treat, are prone to recurrence, and can lead to subfertility or infertility. Knowledge of the interconnected microorganism communities along the continuum of the female reproductive tract could revolutionize the quality of women’s healthcare. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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Other

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27 pages, 1250 KiB  
Systematic Review
The Clinical Trial Outcomes of Cranberry, D-Mannose and NSAIDs in the Prevention or Management of Uncomplicated Urinary Tract Infections in Women: A Systematic Review
by Jenane Konesan, Lu Liu and Kylie J. Mansfield
Pathogens 2022, 11(12), 1471; https://doi.org/10.3390/pathogens11121471 - 05 Dec 2022
Cited by 6 | Viewed by 10160
Abstract
The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence [...] Read more.
The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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