Alzhraa Mohamed

Turkey

Quercetin, a flavonoid suppresses E. coli biofilm genes and possesses antioxidant potential

Alzhraa Ali Mohamed1 · Eslam Abdelhakim Seyam2 · Sameh A. Hussein3 · Mohamed Abdel‐Haleem4
1-Graduate School of Natural and Applied Science, Ege
University, İzmir, Türkiye
2-Department of Insurance and Risk Management, College
of Business, Imam Mohammad Ibn Saud Islamic University
(IMSIU), Riyadh, Saudi Arabia
3- Department of Mathematics, Faculty of Science, Zagazig
University, Zagazig, Egypt
4-Botany and Microbiology Department, Faculty of Science,
Zagazig University, Zagazig 44519, Egypt

Abstract

Background

Escherichia coli is one of the intestinal Enterobacterales commensals which outside intestine can trigger a wide range of infections, involving urinary tract infections, sepsis, and gastrointestinal illnesses. It is top-listed among the six leading causes of AMR-associated deaths in 2019. This study investigates the antibacterial and antibiofilm potential of quercetin against carbapenem and cephalosporin resistant clinical Escherichia coli and evaluating its antioxidant activity.

Methods

In this study 12 clinical E. coli strains were tested for their antibiotic susceptibility to ten antibiotics namely, Ciprofloxacin (5µg), Levofloxacin (5µg), Ceftriaxone(30µg), Cefotaxime (5µg), Amoxicillin-clavulanate (2-1µg), Piperacillin-tazobactam (30-6µg), Trimethoprim-sulfamethoxazole (1.25–23.75µg), Meropenem (10µg), Aztreonam (30µg) and Nitrofurantoin (100µg). The strain E. coli EI was selected as the utmost antibiotic-resistant strain that was further employed in the following experiments. These experiments included evaluation of the antibacterial and antibiofilm activity of quercetin using plate methods (agar-well diffusion and micro-titer plate) and Scanning electron microscopy, followed by assessment of the biofilm gene-expression test using RT-qPCR. Next the antioxidant activity of Quercetin was evaluated by DPPH assay. Further molecular docking studies were performed to evaluate and understand the activity of quercetin on the molecular level.

Results

E.coli-EI preformed biofilm-biomass was eliminated by 53.1% when treated with quercetin (200 mg/mL). Additionally, SEM micrographs of treated biofilms showed elimination of most of the biofilm polysaccharide-matrix, decreased cell density, and cell membrane disruption of some bacterial cells. Furthermore, PCR and RT-qPCR results revealed downregulation of adrA biofilm gene. DPPH assay results indicated that quercetin dose-dependent antioxidant activity with IC₅₀ value of 53.06 mg/mL. Moreover, molecular docking studies revealed that quercetin is able to form several stabilizing interactions like hydrogen bonds and hydrophobic interactions, with AdrA-protein, displaying effective binding-capacity of -6.2 kcal/mol.

Conclusions

The findings of this study emphasize the multifaceted role of quercetin as a potent antibacterial and antioxidant agent. As both wet-lab and computational investigations demonstrate that quercetin reduces the expression of the adrA gene in E. coli, disrupting bacterial virulence and biofilm formation, in addition to its ability to scavenge ROS and
enhance cellular antioxidant defenses underscores its potential to mitigate oxidative stress during bacterial infections. These findings aligning with previous studies position quercetin as a competent natural substitute to regular antibiotics for combating the increased global health menace of antibiotic resistance.