scholarly journals Deacidification by FhlA-dependent hydrogenase is involved in urease activity and urinary stone formation in uropathogenic Proteus mirabilis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wen-Yuan Lin ◽  
Shwu-Jen Liaw
Keyword(s):  
Proteus Mirabilis ◽  
Urease Activity ◽  
Stone Formation ◽  
Large Subunit ◽  
Acid Resistance ◽  
Urinary Stone ◽  
Potential Strategy ◽  
Ph Range ◽  
Tract Infections

Abstract Proteus mirabilis is an important uropathogen, featured with urinary stone formation. Formate hydrogenlyase (FHL), consisting of formate dehydrogenase H and hydrogenase for converting proton to hydrogen, has been implicated in virulence. In this study, we investigated the role of P. mirabilis FHL hydrogenase and the FHL activator, FhlA. fhlA and hyfG (encoding hydrogenase large subunit) displayed a defect in acid resistance. fhlA and hyfG mutants displayed a delay in medium deacidification compared to wild-type and ureC mutant failed to deacidify the medium. In addition, loss of fhlA or hyfG decreased urease activity in the pH range of 5–8. The reduction of urease activities in fhlA and hyfG mutants subsided gradually over the pH range and disappeared at pH 9. Furthermore, mutation of fhlA or hyfG resulted in a decrease in urinary stone formation in synthetic urine. These indicate fhlA- and hyf-mediated deacidification affected urease activity and stone formation. Finally, fhlA and hyfG mutants exhibited attenuated colonization in mice. Altogether, we found expression of fhlA and hyf confers medium deacidification via facilitating urease activity, thereby urinary stone formation and mouse colonization. The link of acid resistance to urease activity provides a potential strategy for counteracting urinary tract infections by P. mirabilis.

scholarly journals Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity

2021 ◽  
Vol 22 (13) ◽  
pp. 7205
Author(s):  
Matheus V. C. Grahl ◽  
Augusto F. Uberti ◽  
Valquiria Broll ◽  
Paula Bacaicoa-Caruso ◽  
Evelin F. Meirelles ◽  
...  
Keyword(s):  
Proteus Mirabilis ◽  
Stone Formation ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Urinary Stone ◽  
Enzymatic Properties ◽  
Hek293 Cells ◽  
Urinary Stones ◽  
Isolated Cells ◽  
Tnf Α

Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.

Chlorpromazine-impregnated catheters as a potential strategy to control biofilm-associated urinary tract infections

2019 ◽  
Vol 14 (12) ◽  
pp. 1023-1034 ◽  
Author(s):  
José JC Sidrim ◽  
Bruno R Amando ◽  
Francisco IF Gomes ◽  
Marilia SMG do Amaral ◽  
Paulo CP de Sousa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Biofilm Formation ◽  
Antibiofilm Activity ◽  
Potential Strategy ◽  
Tract Infections

Aim: This study proposes the impregnation of Foley catheters with chlorpromazine (CPZ) to control biofilm formation by Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae. Materials & methods: The minimum inhibitory concentrations (MICs) for CPZ and the effect of CPZ on biofilm formation were assessed. Afterward, biofilm formation and the effect of ciprofloxacin and meropenem (at MIC) on mature biofilms grown on CPZ-impregnated catheters were evaluated. Results: CPZ MIC range was 39.06–625 mg/l. CPZ significantly reduced (p < 0.05) biofilm formation in vitro and on impregnated catheters. In addition, CPZ-impregnation potentiated the antibiofilm activity of ciprofloxacin and meropenem. Conclusion: These findings bring perspectives for the use of CPZ as an adjuvant for preventing and treating catheter-associated urinary tract infections.

A role of fructose in urinary stone formation

Urologiia ◽  
2019 ◽  
Vol 1_2019 ◽  
pp. 114-118
Author(s):  
Z.Sh. Pavlova Pavlova ◽  
I.I. Golodnikov Golodnikov ◽  
A. A. Kamalov Kamalov ◽  
A.N. Nizov Nizov ◽  
◽  
...  
Keyword(s):  
Stone Formation ◽  
Urinary Stone

scholarly journals Role of RppA in the Regulation of Polymyxin B Susceptibility, Swarming, and Virulence Factor Expression in Proteus mirabilis

2008 ◽  
Vol 76 (5) ◽  
pp. 2051-2062 ◽  
Author(s):  
Won-Bo Wang ◽  
I-Chun Chen ◽  
Sin-Sien Jiang ◽  
Hui-Ru Chen ◽  
Chia-Yu Hsu ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Proteus Mirabilis ◽  
Response Regulator ◽  
Polymyxin B ◽  
Wild Type ◽  
High Concentration ◽  
Knockout Mutant ◽  
Two Component System ◽  
Tract Infections

ABSTRACT Proteus mirabilis, a human pathogen that frequently causes urinary tract infections, is intrinsically highly resistant to cationic antimicrobial peptides, such as polymyxin B (PB). To explore the mechanisms underlying P. mirabilis resistance to PB, a mutant which displayed increased (>160-fold) sensitivity to PB was identified by transposon mutagenesis. This mutant was found to have Tn5 inserted into a novel gene, rppA. Sequence analysis indicated that rppA may encode a response regulator of the two-component system and is located upstream of the rppB gene, which may encode a membrane sensor kinase. An rppA knockout mutant of P. mirabilis had an altered lipopolysaccharide (LPS) profile. The LPS purified from the rppA knockout mutant could bind more PB than the LPS purified from the wild type. These properties of the rppA knockout mutant may contribute to its PB-sensitive phenotype. The rppA knockout mutant exhibited greater swarming motility and cytotoxic activity and expressed higher levels of flagellin and hemolysin than the wild type, suggesting that RppA negatively regulates swarming, hemolysin expression, and cytotoxic activity in P. mirabilis. PB could modulate LPS synthesis and modification, swarming, hemolysin expression, and cytotoxic activity in P. mirabilis through an RppA-dependent pathway, suggesting that PB could serve as a signal to regulate RppA activity. Finally, we demonstrated that the expression of rppA was up-regulated by a low concentration of PB and down-regulated by a high concentration of Mg2+. Together, these data highlight the essential role of RppA in regulating PB susceptibility and virulence functions in P. mirabilis.

MP-19.02: The Role of NF-Kb on Renal Stone Formation: Possibility of the Prevention of Urinary Stone Formation Using Antinf-Kb Reagent, N-Acetyl-L-Cysteine

Urology ◽  
2009 ◽  
Vol 74 (4) ◽  
pp. S135
Author(s):  
K. Tozawa ◽  
A. Okada ◽  
T. Yasui ◽  
B. Gao ◽  
Y. Ito ◽  
...  
Keyword(s):  
Renal Stone ◽  
Stone Formation ◽  
Urinary Stone

DRUG-RELATED URINARY TRACT INFECTIONS

2021 ◽  
Vol 74 (7) ◽  
pp. 1728-1736
Author(s):  
Łukasz Dobrek
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Stone Formation ◽  
Urinary Stone ◽  
Upper Urinary Tract ◽  
Glucose Reabsorption ◽  
Increased Risk ◽  
Specific Manifestation ◽  
Tract Infections ◽  
Common Infection

Bacterial urinary tract infection (UTI) is the most common infection, both in outpatient treatment and in hospital settings. Clinically, UTIs are classified into lower or upper urinary tract infections and can be either episodic or recurrent, and either uncomplicated or complicated. A severe UTI can lead to urosepsis and septic shock, while recurrent episodes of uncomplicated UTIs are considered to be an important etiological factor for the development of chronic kidney disease. The aim of this paper was to briefly discuss the classification, symptomatology and pathophysiology of a UTI and describe the rationale for the development of some drug-related urinary tract infections. The pathophysiology of a UTI is associated with multiple, anatomical and physiological dysfunctions that predispose infection, but there are also some iatrogenic factors, including the use of certain medications, that contribute to UTI development. Among drugs associated with an increased risk of UTI development one should mention immunosuppressants, agents affecting normal voiding processes and increasing the intravesical volume of residual urine, drugs promoting lithogenesis in the urinary tract with the subsequent favouring of urinary stone formation or drugs that reduce glucose reabsorption in the kidneys, causing glycosuria (“gliflozins”). Conclusions: Therefore, a UTI may also be a specific manifestation of adverse drug reactions and it should be taken into account in the monitoring and diagnosing of druginduced disorders.

A role of fructose in urinary stone formation

Urologiia ◽  
2019 ◽  
Vol 1_2019 ◽  
pp. 114-118
Author(s):  
Z.Sh. Pavlova Pavlova ◽  
I.I. Golodnikov Golodnikov ◽  
A. A. Kamalov Kamalov ◽  
A.N. Nizov Nizov ◽  
◽  
...  
Keyword(s):  
Stone Formation ◽  
Urinary Stone

scholarly journals Effect of Curcumin AgainstProteus mirabilisDuring Crystallization of Struvite from Artificial Urine

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Jolanta Prywer ◽  
Agnieszka Torzewska
Keyword(s):  
Urinary Tract Infection ◽  
Proteus Mirabilis ◽  
Crystallization Process ◽  
Crystal Morphology ◽  
Stone Formation ◽  
Urinary Stone ◽  
Urinary Stones ◽  
Artificial Urine ◽  
Struvite Crystallization

We investigated the activity of curcumin againstProteus mirabilisand the struvite crystallization in relation to urinary stones formation. In order to evaluate an activity of curcumin we performed anin vitroexperiment of struvite growth from artificial urine. The crystallization process was induced byProteus mirabilisto mimic the real urinary tract infection, which usually leads to urinary stone formation. The results demonstrate that curcumin exhibits the effect againstProteus mirabilisinhibiting the activity of urease—an enzyme produced by these microorganisms. Addition of curcumin increases the induction time and decreases the efficiency of growth of struvite compared with the absence of curcumin. Interestingly, the addition of curcumin does not affect the crystal morphology and habit. In conclusion, curcumin has demonstrated its significant potential to be further investigated for its use in the case of struvite crystallization induced for the growth byProteus mirabilisin relation to urinary stone formation.

scholarly journals UreR, the Transcriptional Activator of the Proteus mirabilis Urease Gene Cluster, Is Required for Urease Activity and Virulence in Experimental Urinary Tract Infections

2003 ◽  
Vol 71 (2) ◽  
pp. 1026-1030 ◽  
Author(s):  
Jonathan D. Dattelbaum ◽  
C. Virginia Lockatell ◽  
David E. Johnson ◽  
Harry L. T. Mobley
Keyword(s):  
Urinary Tract ◽  
Gene Cluster ◽  
Proteus Mirabilis ◽  
Urease Activity ◽  
Complicated Urinary Tract Infection ◽  
Wild Type ◽  
Urease Gene ◽  
Low Copy Number ◽  
Mutant Strains ◽  
Tract Infections

ABSTRACT Proteus mirabilis, a cause of complicated urinary tract infection, produces urease, an essential virulence factor for this species. UreR, a member of the AraC/XylS family of transcriptional regulators, positively activates expression of the ure gene cluster in the presence of urea. To specifically evaluate the contribution of UreR to urease activity and virulence in the urinary tract, a ureR mutation was introduced into P. mirabilis HI4320 by homologous recombination. The isogenic ureR::aphA mutant, deficient in UreR production, lacked measurable urease activity. Expression was not detected in the UreR-deficient strain by Western blotting with monoclonal antibodies raised against UreD. Urease activity and UreD expression were restored by complementation of the mutant strain with ureR expressed from a low-copy-number plasmid. Virulence was assessed by transurethral cochallenge of CBA mice with wild-type and mutant strains. The isogenic ureR::aphA mutant of HI4320 was outcompeted in the urine (P = 0.004), bladder (P = 0.016), and kidneys (P ≤ 0.001) 7 days after inoculation. Thus, UreR is required for basal urease activity in the absence of urea, for induction of urease by urea, and for virulence of P. mirabilis in the urinary tract.

scholarly journals MP10-16 THE ROLE OF ONCOSTATIN M IN URINARY STONE FORMATION

2020 ◽  
Vol 203 ◽  
pp. e131-e132
Author(s):  
Shimpei Yamashita* ◽  
Tadasuke Komori ◽  
Yasuo Kohjimoto ◽  
Yoshihiro Morikawa ◽  
Hara Isao
Keyword(s):  
Stone Formation ◽  
Urinary Stone ◽  
Oncostatin M
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