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Pathogens
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Virulence Mechanisms of Uropathogenic Bacteria
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Virulence Mechanisms of Uropathogenic Bacteria

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 8433

Special Issue Editors

Dr. Ritwij Kulkarni

E-Mail Website
Guest Editor
Department of Biology, University of Louisiana at Lafayette, Lafayette, Louisiana, USA
Interests: urinary tract infections (UTI); diabetic UTI; uropathogenic Escherichia coli (UPEC); methicillin resistant Staphylococcus aureus (MRSA); group B Streptococcus (GBS); Streptococcus agalactiae; NLRP3 inflammasome
Dr. Jennifer N. Walker

E-Mail Website
Guest Editor
Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, TX, USA
Interests: catheter-associated urinary tract infections (CAUTIs); methicillin resistant Staphylococcus aureus (MRSA); Pseudomonas aeruginosa; Klebsiella pneumonia; catheter-induced bladder inflammation

Special Issue Information

Dear Colleagues,

Urinary tract infections (UTI) are a highly prevalent disease that is considered a major public health concern across the globe due to the continual emergence of antibiotic-resistant uropathogens. Over the last two decades, researchers have sought to improve our understanding of the specific bacterial fitness, virulence mechanisms, and host susceptibilities important for urinary pathogenesis with an eye towards developing novel therapeutic strategies. The main focus of these studies have been the Gram-negative uropathogenic Escherichia coli (UPEC), which causes a vast majority of both uncomplicated hospital- and community-acquired UTIs. Yet, in recent years, the importance of additional uropathogens, particularly in the context of complicated UTIs, such as those that occur in pregnant women, the elderly, individuals with diabetes, or with urinary catheters, have been highlighted. Many studies indicate that UTIs in these populations are frequently caused by Gram-negative bacteria other than UPEC or Gram-positive uropathogens. Furthermore, for those with urinary catheters, UTIs are increasingly polymicrobial, which adds additional challenges during treatment in this population.

For this Special Issue, we seek manuscripts examining the physiology of uropathogens in the urinary microenvironment. We are interested in manuscripts examining global transcriptomes/metabolomes of uropathogens isolated from infected mice or humans as well as manuscripts comparing WT and specific virulence gene knockout mutants side-by-side in mouse models of uncomplicated, ascending, or complicated UTIs. In additon to UPEC, uropathogens of interest include, but are not limited to, Klebsiella pneumoniae, Proteus spp., group B Streptococcus (GBS), methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and Pseudomonas aeruginosa.

Dr. Ritwij Kulkarni
Dr. Jennifer N. Walke
Guest Editors

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

  • urinary tract infections
  • UTI
  • uropathogens
  • uropathogenic Escherichia coli
  • UPEC

Published Papers (4 papers)

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Research

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10 pages, 2221 KiB  
Article
The NLRP3 Inflammasome Is Dispensable in Methicillin-Resistant Staphylococcus aureus Urinary Tract Infection
by Santosh Paudel, Rahul Kumar, Kenneth A. Rogers, Yogesh Saini, Sonika Patial and Ritwij Kulkarni
Pathogens 2024, 13(2), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens13020106 - 25 Jan 2024
Viewed by 947
Abstract
The NLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1β and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is [...] Read more.
The NLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1β and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is activated in the urinary tract by a variety of infectious and non-infectious insults. In this study, we investigated the role of the NLRP3 inflammasome by comparing the pathophysiology of methicillin-resistant Staphylococcus aureus (MRSA) ascending UTI in wild-type (WT) and Nlrp3−/− mice. The difference in the bacterial burden detected in the urinary tracts of MRSA-infected WT and Nlrp3−/− was not statistically significant at 6, 24, and 72 h post-infection (hpi). The levels of pro-inflammatory cytokines and chemokines as well as the numbers of granulocytes recruited to bladder and kidney tissues at 24 hpi were also similar between Nlrp3−/− and WT mice. The histopathological analysis of MRSA-infected bladder and kidney sections from Nlrp3−/− and WT mice showed similar inflammation. Overall, these results suggest that MRSA-induced urinary NLRP3 activity does not play a role in the pathophysiology of the ascending UTI. Full article
(This article belongs to the Special Issue Virulence Mechanisms of Uropathogenic Bacteria)
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14 pages, 1682 KiB  
Article
FimH and Type 1 Pili Mediated Tumor Cell Cytotoxicity by Uropathogenic Escherichia coli In Vitro
by Shelly Roselyn Van Eyssen, Anastasia Samarkina, Ovgu Isbilen, Merve Suzan Zeden and Ender Volkan
Pathogens 2023, 12(6), 751; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12060751 - 23 May 2023
Cited by 1 | Viewed by 1558
Abstract
Uropathogenic Escherichia coli express hairlike proteinaceous surface projections, known as chaperone–usher pathway (CUP) pili. Type 1 pili are CUP pili with well-established pathogenic properties. The FimH adhesin subunit of type 1 pili plays a key role in the pathogenesis of urinary tract infections [...] Read more.
Uropathogenic Escherichia coli express hairlike proteinaceous surface projections, known as chaperone–usher pathway (CUP) pili. Type 1 pili are CUP pili with well-established pathogenic properties. The FimH adhesin subunit of type 1 pili plays a key role in the pathogenesis of urinary tract infections (UTIs) as it mediates the adhesion of the bacteria to urothelial cells of the bladder. In this study, two breast cancer cell lines, MDA-MB-231 and MCF-7, were used to demonstrate the cytotoxic activities of type 1 piliated uropathogenic E. coli UTI89 on breast cancer cells in a type 1 pili and FimH-mediated manner. E. coli were grown in static and shaking conditions to induce or inhibit optimal type 1 pili biogenesis, respectively. Deletion constructs of UTI89 ΔfimH and a complemented strain (UTI89 ΔfimH/pfimH) were further utilized to genetically assess the effect of type 1 pili and FimH on cancer cell viability. After incubation with the different strains, cytotoxicity was measured using trypan blue exclusion assays. UTI89 grown statically caused significant cytotoxicity in both breast cancer cell lines whereas cytotoxicity was reduced when the cells were incubated with bacteria grown under shaking conditions. The incubation of both MDA-MB-231 and MCF-7 with UTI89 Δfim operon or ΔfimH showed a significant reduction in cytotoxicity exerted by the bacterial strains, revealing that type 1 pili expression was necessary for cytotoxicity. Complementing the ΔfimH strain with pfimH reversed the phenotype, leading to a significant increase in cytotoxicity. Incubating type 1 pili expressing bacteria with the competitive FimH inhibitor D-mannose before cancer cell treatment also led to a significant reduction in cytotoxicity on both MDA-MB-231 and MCF-7 cancer cells, compared to vehicle control or D-mannose alone, indicating the requirement for functional FimH for cytotoxicity. Overall, our results reveal that, as opposed to UTI89 lacking type 1 pili, type 1 piliated UTI89 causes significant cancer cell mortality in a FimH-mediated manner, that is decreased with D-mannose. Full article
(This article belongs to the Special Issue Virulence Mechanisms of Uropathogenic Bacteria)
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Review

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24 pages, 643 KiB  
Review
In Vivo Role of Two-Component Regulatory Systems in Models of Urinary Tract Infections
by Giuseppe Valerio De Gaetano, Germana Lentini, Agata Famà, Francesco Coppolino and Concetta Beninati
Pathogens 2023, 12(1), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010119 - 10 Jan 2023
Cited by 3 | Viewed by 2805
Abstract
Two-component signaling systems (TCSs) are finely regulated mechanisms by which bacteria adapt to environmental conditions by modifying the expression of target genes. In bacterial pathogenesis, TCSs play important roles in modulating adhesion to mucosal surfaces, resistance to antibiotics, and metabolic adaptation. In the [...] Read more.
Two-component signaling systems (TCSs) are finely regulated mechanisms by which bacteria adapt to environmental conditions by modifying the expression of target genes. In bacterial pathogenesis, TCSs play important roles in modulating adhesion to mucosal surfaces, resistance to antibiotics, and metabolic adaptation. In the context of urinary tract infections (UTI), one of the most common types infections causing significant health problems worldwide, uropathogens use TCSs for adaptation, survival, and establishment of pathogenicity. For example, uropathogens can exploit TCSs to survive inside bladder epithelial cells, sense osmolar variations in urine, promote their ascension along the urinary tract or even produce lytic enzymes resulting in exfoliation of the urothelium. Despite the usefulness of studying the function of TCSs in in vitro experimental models, it is of primary necessity to study bacterial gene regulation also in the context of host niches, each displaying its own biological, chemical, and physical features. In light of this, the aim of this review is to provide a concise description of several bacterial TCSs, whose activity has been described in mouse models of UTI. Full article
(This article belongs to the Special Issue Virulence Mechanisms of Uropathogenic Bacteria)
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Other

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9 pages, 6500 KiB  
Case Report
Xanthogranulomatous Pyelonephritis Caused by Stenotrophomonas maltophilia—The First Case Report and Brief Review
by Răzvan-Cosmin Petca, Răzvan-Alexandru Dănău, Răzvan-Ionuț Popescu, Daniel Damian, Cristian Mareș, Aida Petca and Viorel Jinga
Pathogens 2022, 11(1), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11010081 - 10 Jan 2022
Cited by 3 | Viewed by 1913
Abstract
Xanthogranulomatous pyelonephritis (XGP) represents a rare and severe pathology secondary to chronic urinary obstruction and recurrent infections. Commonly, this condition leads to loss of kidney function, and frequently, surgical approach is the only optional treatment. Proteus mirabilis and Escherichia coli are the most [...] Read more.
Xanthogranulomatous pyelonephritis (XGP) represents a rare and severe pathology secondary to chronic urinary obstruction and recurrent infections. Commonly, this condition leads to loss of kidney function, and frequently, surgical approach is the only optional treatment. Proteus mirabilis and Escherichia coli are the most frequent pathogens associated with XGP. The actual changes in the pathogen’s characteristics increased the risk of newly acquired infections once considered opportunistic. Stenotrophomonas malthophilia is one of those agents more related to immunocompromised patients, presenting an increased incidence and modified antibiotic resistance profile in the modern era. This case report presents a healthy female patient with an underlying renal stone pathology diagnosed with XGP related to S. maltophilia urinary infection. After a complete biological and imagistic evaluation, the case was treated as pyonephrosis. Empirical antibiotic administration and a surgical approach were considered. A total nephrectomy was performed, but the patient’s condition did not improve. The patient’s status improved when specific antibiotics were administered based on the bacterial identification and antibiotic susceptibility pattern of drained perinephric fluid. Levofloxacin and Vancomycin were considered the optimal combination in this case. The histopathological examination revealed XGP secondary to chronic renal stone. The present study describes the first case of XGP related to an aerobic Gram-negative pathogen such as S. maltophilia, once considered opportunistic, in an apparently healthy female adult. Full article
(This article belongs to the Special Issue Virulence Mechanisms of Uropathogenic Bacteria)
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