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Volume 15
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10.3390/ph15030385
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Article

Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence

by
Marija Ivanov
1,*,
Katarina Novović
2,
Milka Malešević
2,
Miroslav Dinić
2,
Dejan Stojković
1,
Branko Jovčić
2,3 and
Marina Soković
1
1
Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
2
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444A, 11042 Belgrade, Serbia
3
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2022, 15(3), 385; https://doi.org/10.3390/ph15030385
Submission received: 20 February 2022 / Revised: 18 March 2022 / Accepted: 19 March 2022 / Published: 21 March 2022
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)
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Abstract

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin’s ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI, lasR, rhlI, rhlR, pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials.
Keywords: polyphenols; rutin; antibiotic resistance; bacteria; antimicrobial activity; antibiofilm activity; cytotoxicity; virulence; mechanism of activity polyphenols; rutin; antibiotic resistance; bacteria; antimicrobial activity; antibiofilm activity; cytotoxicity; virulence; mechanism of activity

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MDPI and ACS Style

Ivanov, M.; Novović, K.; Malešević, M.; Dinić, M.; Stojković, D.; Jovčić, B.; Soković, M. Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence. Pharmaceuticals 2022, 15, 385. https://doi.org/10.3390/ph15030385

AMA Style

Ivanov M, Novović K, Malešević M, Dinić M, Stojković D, Jovčić B, Soković M. Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence. Pharmaceuticals. 2022; 15(3):385. https://doi.org/10.3390/ph15030385

Chicago/Turabian Style

Ivanov, Marija, Katarina Novović, Milka Malešević, Miroslav Dinić, Dejan Stojković, Branko Jovčić, and Marina Soković. 2022. "Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence" Pharmaceuticals 15, no. 3: 385. https://doi.org/10.3390/ph15030385

APA Style

Ivanov, M., Novović, K., Malešević, M., Dinić, M., Stojković, D., Jovčić, B., & Soković, M. (2022). Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence. Pharmaceuticals, 15(3), 385. https://doi.org/10.3390/ph15030385

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