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image of Integrated Evaluation of IL-8 Levels and the In Silico and In Vitro Effects of Ellagic Acid against Extended-spectrum β-lactamase in Biofilm-forming Klebsiella pneumoniae Isolated from Urinary Tract Infections

Abstract

Introduction

Urinary tract infections (UTIs) caused by multidrug-resistant, biofilm-forming represent a serious global health concern. Conventional antibiotics often fail due to resistance and biofilm-associated tolerance, necessitating novel diagnostic and therapeutic strategies. This study investigated interleukin-8 (IL-8) as a diagnostic marker and evaluated the anti-virulence potential of ellagic acid against extended-spectrum β-lactamase (ESBL)-producing .

Methods

This study was a cross-sectional, experimental, and analytical investigation conducted from August 2023 to March 2024. Serum IL-8 levels were quantified in patients and healthy controls using ELISA. The antibiotic susceptibility of isolates was assessed according to CLSI guidelines, and ESBL activity was determined by the nitrocefin hydrolysis test. Biofilm formation was quantified using the crystal violet assay, with and without ellagic acid treatment. docking studies were conducted using AutoDock Vina to predict interactions between ellagic acid and the CTX-M-15 β-lactamase, Wza, FabH, and SdiA proteins.

Results

IL-8 levels were significantly higher in patients (223.8 ± 43.5 pg/mL) compared with controls (47.9 ± 17.3 pg/mL; < 0.0001). All isolates were resistant to ampicillin and showed broad resistance to other antibiotics. Ellagic acid significantly reduced biofilm biomass ( = 0.0002) but concurrently increased ESBL activity ( = 0.0001). Docking demonstrated that ellagic acid was strongly bound to CTX-M-15 (-8.3 kcal/mol), had moderate interactions with Wza and SdiA, whereas the interaction with FabH was relatively low.

Discussion

The high concentration of IL-8 supports its use as a biomarker to detect infections. The elevated resistance profile of to antibiotics highlights the urgent need for alternative treatment approaches. Though ellagic acid increased ESBL activity, it showed distinct antibiofilm activity and responses with virulence-related proteins, indicating a modulatory action that may reduce bacterial pathogenicity. Limitations include the lack of validation and the need to mechanistically elucidate the modulation of ESBL.

Conclusion

IL-8 is a valuable biomarker for ESBL-producing infection. Ellagic acid reduces biofilm formation and targets bacterial resistance and virulence proteins, supporting its potential as a natural anti-virulence agent against multidrug-resistant .

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2026-05-10

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Integrated Evaluation of IL-8 Levels and the In Silico and In Vitro Effects of Ellagic Acid against Extended-spectrum β-lactamase in Biofilm-forming Klebsiella pneumoniae Isolated from Urinary Tract Infections
Bentham Science Publishers ; https://doi.org/10.2174/0115748871349421251105115035
/content/journals/rrct/10.2174/0115748871349421251105115035
/content/journals/rrct/10.2174/0115748871349421251105115035
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  • Article Type:     Research Article
Keywords: Ellagic acid ; biofilm ; IL-8 ; UTI ; Klebsiella pneumoniae ; ESBLs ; molecular docking

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