Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties

Mulat, Mulugeta; Banicod, Riza Jane S.; Tabassum, Nazia; Javaid, Aqib; Karthikeyan, Abirami; Jeong, Geum-Jae; Kim, Young-Mog; Jung, Won-Kyo; Khan, Fazlurrahman

doi:10.3390/antibiotics14060555

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Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties

by

Mulugeta Mulat

^1,†

,

Riza Jane S. Banicod

^2,†

,

Nazia Tabassum

^3,4,†

,

Aqib Javaid

⁵,

Abirami Karthikeyan

⁶,

Geum-Jae Jeong

^3,4,7

,

Young-Mog Kim

^3,4,7

,

Won-Kyo Jung

^3,4,8

and

Fazlurrahman Khan

^3,4,5,9,10,*

¹

Department of Biotechnology, School of Bioscience and Technology, College of Natural Sciences, Wollo University, Dessie 1145, Ethiopia

²

Fisheries Postharvest Research and Development Division, National Fisheries Research and Development Institute, Quezon City 1128, Philippines

³

Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea

⁴

Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea

⁵

Interdisciplinary Program of Marine and Fisheries Sciences and Convergent Technology, Pukyong National University, Busan 48513, Republic of Korea

⁶

Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Republic of Korea

⁷

Department of Food Science and Technology, Pukyong National University, Busan 48513, Republic of Korea

⁸

Major of Biomedical Engineering, Division of Smart Healthcare, College of Information Technology and Convergence and New-Senior Healthcare Innovation Center (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea

⁹

Ocean and Fisheries Development International Cooperation Institute, Pukyong National University, Busan 48513, Republic of Korea

¹⁰

International Graduate Program of Fisheries Science, Pukyong National University, Busan 48513, Republic of Korea

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Antibiotics 2025, 14(6), 555; https://doi.org/10.3390/antibiotics14060555

Submission received: 30 April 2025 / Revised: 17 May 2025 / Accepted: 28 May 2025 / Published: 29 May 2025

(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)

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Abstract

Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical contexts such as device-associated infections and chronic wounds. Secondary metabolites derived from medicinal plants, such as alkaloids, tannins, flavonoids, phenolic acids, and essential oils, have gained attention as promising agents against biofilm formation, microbial virulence, and antibiotic resistance. These natural compounds not only limit microbial growth and biofilm development but also disrupt communication between bacteria, known as quorum sensing, which reduces their ability to cause disease. Through progress in nanotechnology, various nanocarriers such as lipid-based systems, polymeric nanoparticles, and metal nanoparticles have been developed to improve the solubility, stability, and cellular uptake of phytochemicals. In addition, the synergistic use of plant-based metabolites with conventional antibiotics or antifungal drugs has shown promise in tackling drug-resistant microorganisms and revitalizing existing drugs. This review comprehensively discusses the efficacy of pure secondary metabolites from medicinal plants, both as individuals and in nanoformulated forms or in combination with antimicrobial agents, as alternative strategies to control biofilm-forming pathogens. The molecular mechanisms underlying their antibiofilm and antivirulence activities are discussed in detail. Lastly, the current pitfalls, limitations, and emerging directions in translating these natural compounds into clinical applications are critically evaluated.

Keywords: antimicrobial resistance; medicinal plant secondary metabolites; biofilm inhibition; virulence attenuation; nanoformulations for biofilm control; drug combination

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MDPI and ACS Style

Mulat, M.; Banicod, R.J.S.; Tabassum, N.; Javaid, A.; Karthikeyan, A.; Jeong, G.-J.; Kim, Y.-M.; Jung, W.-K.; Khan, F. Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties. Antibiotics 2025, 14, 555. https://doi.org/10.3390/antibiotics14060555

AMA Style

Mulat M, Banicod RJS, Tabassum N, Javaid A, Karthikeyan A, Jeong G-J, Kim Y-M, Jung W-K, Khan F. Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties. Antibiotics. 2025; 14(6):555. https://doi.org/10.3390/antibiotics14060555

Chicago/Turabian Style

Mulat, Mulugeta, Riza Jane S. Banicod, Nazia Tabassum, Aqib Javaid, Abirami Karthikeyan, Geum-Jae Jeong, Young-Mog Kim, Won-Kyo Jung, and Fazlurrahman Khan. 2025. "Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties" Antibiotics 14, no. 6: 555. https://doi.org/10.3390/antibiotics14060555

APA Style

Mulat, M., Banicod, R. J. S., Tabassum, N., Javaid, A., Karthikeyan, A., Jeong, G.-J., Kim, Y.-M., Jung, W.-K., & Khan, F. (2025). Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties. Antibiotics, 14(6), 555. https://doi.org/10.3390/antibiotics14060555

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Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties

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