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Antibiotics
Special Issues
Innovations in Plant-Based Antibiotic and Antiviral Agents
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Innovations in Plant-Based Antibiotic and Antiviral Agents

A Special Issue of Antibiotics (ISSN 2079-6382) belonging to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: closed (31 July 2026) | Viewed by 9606

Editors

Dr. Margherita-Gabriella De Biasi

E-Mail Website
Guest Editor
Department of Pharmacy, University of Naples Federico II, Via Montesano 49, 80131 Napoli, Italy
Interests: plant secondary metabolites; antimicrobial effects of phytochemical components; biochemistry and biotechnology; plant-derived antibiotics; plant responses to stresses phytoremediation
Special Issues, Collections and Topics in MDPI journals
Dr. Irene Dini

E-Mail Website
Guest Editor
Department of Pharmacy, University of Naples Federico II, Via Montesano 49, 80131 Napoli, Italy
Interests: food chemistry; food toxology; analytical chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotics and antivirals, which can be either naturally occurring or artificially created organic compounds, are drugs that can act against bacteria, fungi and viruses. However, in recent years, a severe threat to human health has arisen worldwide as many antibiotics and antivirals have become inactive due to resistance phenomena, and no new treatments have been developed. A natural alternative to synthetic antibiotics and antivirals involves the use of plants, plant extracts, or secondary metabolites isolated from the latter, with antimicrobial action. Alkaloids, terpenoids, steroids, tannins, flavonoids, coumarins, essential oils, and lectins are some examples of phytochemicals able to act against parasites. They can modulate antibiotic and antiviral susceptibility, attenuate bacterial virulence, and inhibit the microbial synthesis of the cell wall, physiology, and biofilm. Phytochemicals have the advantage of being more accepted by consumers who prefer using natural products and that they do not generate microbial resistance phenomena. Thus, antimicrobials and antivirals derived from plants, whether used independently or in conjunction with antibiotics, can contribute to addressing the current issue of antibiotic resistance. In particular, the following topics are of interest:

  • Isolation and identification of antimicrobial secondary metabolites from plants;
  • Isolation and identification of antiviral secondary metabolites from plants;
  • Validation of analytical methods used to detect phytochemicals;
  • Pharmacognosy studies (in vitro and in vivo assays);
  • Pharmacology studies (in vitro and in vivo assays);
  • Toxicity studies (in vitro and in vivo assays);
  • Antimicrobial activities;
  • Antiviral activities.

Dr. Margherita-Gabriella De Biasi
Dr. Irene Dini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • secondary metabolites
  • phytochemicals
  • botanicals
  • analytical methods
  • toxicity

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Published Papers (5 papers)

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Research

10 pages, 422 KB  
Article
Cinnamon Essential Oil: A Promising Natural Strategy for the Prevention of Rabbit Colibacillosis
by Gaia Casalino, Davide Messina, Roberta Tardugno, Giuseppe Fracchiolla, Giancarlo Bozzo, Dalila Salierno, Francesco D’Amico, Martina Canale, Antonella Bove, Antonio Camarda and Elena Circella
Antibiotics 2026, 15(9), 840; https://doi.org/10.3390/antibiotics15090840 (registering DOI) - 30 Aug 2026
Abstract
Background/Objectives: Colibacillosis, caused by enteropathogenic strains of Escherichia coli (EPEC), is one of the most common infectious diseases in rabbit farms. In the past, antimicrobials were widely used to control colibacillosis, but their use in prevention is currently prohibited. Therefore, the adoption of [...] Read more.
Background/Objectives: Colibacillosis, caused by enteropathogenic strains of Escherichia coli (EPEC), is one of the most common infectious diseases in rabbit farms. In the past, antimicrobials were widely used to control colibacillosis, but their use in prevention is currently prohibited. Therefore, the adoption of new prevention strategies as alternatives to the use of antibiotics is very important. The aim of this study was to evaluate the antimicrobial efficacy of cinnamon essential oil (Cinnamomum zeylanicum) against EPEC strains responsible for colibacillosis in rabbits. Methods: For the experiment, 124 strains of E. coli isolated from rabbits that had died of colibacillosis in 10 industrial farms were used. Suspensions of each strain prepared according to CLSI standards with a bacterial density of 1 × 108 CFU/mL were tested using 100% pure commercial cinnamon essential oil (CEO) at concentrations ranging from 0.2 to 0.8 μL/mL. Minimum inhibitory concentrations MIC50 and MIC90 were determined according to a protocol described previously. Results: MIC50 and MIC90 were 0.5 μL/mL and 0.6 μL/mL, inhibiting 64.5% and 94.3% of strains, respectively. Furthermore, strains exposed to 0.4 μL/mL were 12.9 times more likely to be inhibited than those exposed to 0.3 μL/mL (p = 0.0001). Conclusions: CEO was found to be effective against E. coli strains tested at high bacterial densities that can usually be found per gram of faeces in rabbits affected by colibacillosis. Consequently, cinnamon should be useful in preventing colibacillosis by limiting the replication of E. coli, as it is usually found in lower densities in the intestines of healthy rabbits, preventing the onset of colibacillosis and reducing the use of antibiotics in rabbit farms. Full article
(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)
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21 pages, 2104 KB  
Article
Solidagoic Acids L and M: Novel Antibacterial cis-Clerodane Diterpenoids Isolated from the Inflorescences of Solidago gigantea via a Bioassay-Guided Approach
by Márton Baglyas, Zoltán Bozsó and Ágnes M. Móricz
Antibiotics 2026, 15(7), 687; https://doi.org/10.3390/antibiotics15070687 - 14 Jul 2026
Viewed by 511
Abstract
Background/Objectives: Plant secondary metabolites remain an invaluable source of novel antibacterial phytochemicals in the fight against antibiotic resistance. The medicinal plant Solidago gigantea Ait. (giant goldenrod) is an invasive species in Europe and represents an abundant, yet largely underexplored reservoir of such [...] Read more.
Background/Objectives: Plant secondary metabolites remain an invaluable source of novel antibacterial phytochemicals in the fight against antibiotic resistance. The medicinal plant Solidago gigantea Ait. (giant goldenrod) is an invasive species in Europe and represents an abundant, yet largely underexplored reservoir of such bioactive compounds. The primary aim of this study was to perform a non-targeted, effect-directed screening, detection, bioassay-guided isolation, structure elucidation, and microbiological assessment of the antibacterial constituents present in the inflorescences of S. gigantea. Methods: Thin-layer chromatography coupled with direct bioautography (TLC–DB) assay using Bacillus subtilis was utilized for the non-targeted, effect-directed analysis of antibacterial components and the evaluation of in vitro antibacterial activity. Successive preparative flash column chromatography, semi-preparative reversed-phase high-performance liquid chromatography (RP-HPLC), and thin-layer chromatography–mass spectrometry (TLC–MS) were employed for the bioassay-guided fractionation and isolation. The structures of the isolated compounds were elucidated using one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution tandem mass spectrometry (HRMS/MS). The presence of known antibacterial compounds was established via reversed-phase ultra-high-performance liquid chromatography coupled with high-resolution electrospray ionization tandem mass spectrometry (RP-UHPLC–HR-ESI-MS/MS). Results: Two previously undescribed cis-clerodane diterpenoids, the isomeric solidagoic acid L (1) and solidagoic acid M (2), were isolated, identified, and characterized from the ethyl acetate extract of S. gigantea inflorescences. Both compounds exhibited in vitro antibacterial activity against the Gram-positive B. subtilis, confirmed via TLC–DB. In addition, 23 known compounds with antibacterial activity, including 17 clerodane diterpenes, four hydroxylated polyunsaturated fatty acids, and two unsaturated monoacylglycerols, were detected. All of these are reported for the first time in the inflorescences of this plant species. Conclusions: With further optimization, the isolated compounds may represent promising leads for antibacterial drug development. Our findings demonstrate the potential of non-targeted, bioassay-guided approaches for the discovery of novel plant-derived bioactive natural products. Full article
(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)
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28 pages, 5156 KB  
Article
Biochanin A, a Plant Isoflavone, Disrupts Peptidoglycan Biosynthesis by Downregulating femA and femB, and Impairs Cell Wall Integrity in Multidrug-Resistant Staphylococcus aureus
by Jade Joshua R. Teodosio, Kathryn Ann H. Dizon, Julyanna R. Bruna, Jan Vincent N. Sollesta, Zenith M. Villorente, Jonel P. Saludes and Doralyn S. Dalisay
Antibiotics 2026, 15(2), 195; https://doi.org/10.3390/antibiotics15020195 - 10 Feb 2026
Cited by 2 | Viewed by 1948
Abstract
Background/Objectives: The global rise in multidrug-resistant Staphylococcus aureus (MDR-SA) threatens the efficacy of existing antibiotics and necessitates alternative antibacterial strategies. Plant-derived isoflavones represent a promising but underexplored source of novel antimicrobials. Biochanin A, isolated from Cajanus cajan seeds, exhibits antibacterial activity and [...] Read more.
Background/Objectives: The global rise in multidrug-resistant Staphylococcus aureus (MDR-SA) threatens the efficacy of existing antibiotics and necessitates alternative antibacterial strategies. Plant-derived isoflavones represent a promising but underexplored source of novel antimicrobials. Biochanin A, isolated from Cajanus cajan seeds, exhibits antibacterial activity and may act via noncanonical mechanisms. This study elucidates the mechanism of action and safety profile of Biochanin A against MDR-SA using integrated experimental and computational approaches. Methods: Antibacterial activity was assessed by minimum inhibitory concentration (MIC) testing. Membrane integrity and morphological alterations were evaluated using flow cytometry and scanning electron microscopy (SEM), respectively. Target gene modulation was analyzed by qRT-PCR, while molecular interactions were examined through in silico docking. Cytotoxicity was evaluated in normal mammalian kidney, liver, and cardiac cells. Results: Biochanin A inhibited MDR-SA with an MIC80 of 64 µg/mL. Flow cytometry showed membrane disruption in 74.46 ± 13.19% of treated cells, and SEM revealed a 20% reduction in cell size (561.95 ± 21.99 nm). Biochanin A markedly downregulated femA (94%) and femB (67%), with minimal effect on femX (10%). Docking analyses supported preferential binding to FemA (−7.7 kcal/mol) and FemB (−7.5 kcal/mol) proteins. No cytotoxic effects were observed in normal mammalian cells. Conclusions: Biochanin A is a promising plant-derived antibacterial candidate against MDR-SA, targeting key cell wall biosynthesis genes while maintaining mammalian safety. These findings position Biochanin A as a viable lead for further biochemical, structural, and in vivo pharmacological validation, highlighting the translational potential of plant-derived isoflavones in combating antibiotic resistance. Full article
(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)
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14 pages, 4961 KB  
Article
Cranberry-Derived Phenolic Compounds Contribute to the Inhibition of FimH-Mediated Escherichia coli Hemagglutination
by Rosana Ribić, Vesna Petrović Peroković, Tomislav Meštrović, Marijana Neuberg and Nikola Bradić
Antibiotics 2025, 14(4), 418; https://doi.org/10.3390/antibiotics14040418 - 21 Apr 2025
Cited by 7 | Viewed by 2736
Abstract
Background/Objectives: FimH adhesin, located at the tips of type 1 pili in Escherichia coli (E. coli), plays a crucial role in bacterial adhesion to the surface urothelial cells—a key step in the pathogenesis of urinary tract infections (UTIs). Given the rising [...] Read more.
Background/Objectives: FimH adhesin, located at the tips of type 1 pili in Escherichia coli (E. coli), plays a crucial role in bacterial adhesion to the surface urothelial cells—a key step in the pathogenesis of urinary tract infections (UTIs). Given the rising concern over antimicrobial resistance (AMR), and considering that E. coli is one of the pathogens with the largest AMR burdens on a global scale, alternative strategies targeting bacterial adhesion are gaining increasing attention. Products that contain D-mannose and cranberry-derived phenolic compounds have shown promise in preventing E. coli colonization and infection. The aim of this study was to investigate the antiadhesive effects of cranberry-related phenolic compounds on FimH-mediated E. coli adhesion using a cellular hemagglutination inhibition assay, as well as to assess the synergistic effects of mannose and phenolic compounds on biofilm formation. Methods: A range of phenolic acids (benzoic, chlorogenic, hippuric, p-coumaric, ferulic and caffeic), resveratrol, (+)-catechin and procyanidin A, as well as a Vaccinium macrocarpon extract, were evaluated for their ability to inhibit FimH-mediated adhesion. A binocular microscope was used to observe agglutination, and we also evaluated the biofilm inhibition potential of the phenolic compounds in the presence of D-mannose. Results: Our results demonstrated that these compounds significantly reduced hemagglutination, with benzoic acid, chlorogenic acid, caffeic acid and resveratrol exhibiting strong inhibitory effects at concentrations as low as 0.25 mM. Furthermore, the addition of 1 mM solutions of these phenolic compounds to D-mannose resulted in a twofold reduction in the inhibition titer, suggesting synergistic interactions. In addition to their antiadhesive properties, the tested phenolic compounds contributed slightly to the inhibition of FimH-mediated biofilm formation, further supporting their potential roles in UTI prevention. Conclusions: These findings highlight the potential of cranberry-derived phenolics as natural antiadhesive agents against E. coli and warrant further investigation into their mechanisms of action and possible applications in infection control. Full article
(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)
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20 pages, 4288 KB  
Article
Eisenia bicyclis-Mediated Gold Nanoparticles Exhibit Antibiofilm and Antivirulence Activities Against Pseudomonas aeruginosa and Staphylococcus aureus
by Do Kyung Oh, Du-Min Jo, Nam-Gyun Kim, Kyung-Jin Cho, Geum-Jae Jeong, Nazia Tabassum, Won-Kyo Jung, Fazlurrahman Khan and Young-Mog Kim
Antibiotics 2025, 14(2), 182; https://doi.org/10.3390/antibiotics14020182 - 11 Feb 2025
Cited by 9 | Viewed by 3050
Abstract
Background/Objectives: Brown algae, particularly Eisenia bicyclis, produce various bioactive chemicals with significant application potential in the food, cosmetics, and pharmaceutical industries. This study aimed to evaluate the antibacterial, antibiofilm, and antivirulence properties of the ethyl acetate fraction (EA) of E. bicyclis and [...] Read more.
Background/Objectives: Brown algae, particularly Eisenia bicyclis, produce various bioactive chemicals with significant application potential in the food, cosmetics, and pharmaceutical industries. This study aimed to evaluate the antibacterial, antibiofilm, and antivirulence properties of the ethyl acetate fraction (EA) of E. bicyclis and its synthesized gold nanoparticles (EA-AuNPs), with a focus on their potential applications against both Gram-positive and Gram-negative bacteria. Methods: The bioactive component in the ethyl acetate fraction was identified using a gas chromatography-mass spectroscopy (GC-MS) device and a liquid chromatography-mass spectrometer/mass spectrometry (LC-MS) system. The crystal violet method was utilized to evaluate the biofilm inhibition experiments. Several instruments, including dynamic light scattering, Fourier transform infrared, X-ray diffraction, field emission transmission electron microscopy, and energy-dispersive spectroscopy, were employed to completely characterize the produced EA-AuNPs. The cytotoxicity of the EA-AuNPs was determined using the MTT assay, and the expression of genes linked with biofilm and virulence in Pseudomonas aeruginosa and Staphylococcus aureus was investigated using real-time polymerase chain reaction (RT-PCR). Results: Various bioactive compounds were identified from the EA using GC-MS and LC-MS, including fatty acids and phlorotannins such as eckol, dieckol, 6,6’-bieckol, and phlorofucofuroeckol in high amounts, highlighting EA as a phlorotannin-rich fraction. The EA also demonstrated significant antibiofilm activity, with 79.86% inhibition at 512 μg/mL against P. aeruginosa and 87.00% at 64 μg/mL against S. aureus. EA was then used in the synthesis of gold nanoparticles (AuNPs) to improve their stability and safety. The synthesized EA-AuNPs were determined to have an average size of 165.04 nm, with a zeta potential of −29.86 mV, indicating good stability. In antibiofilm activity assays, EA-AuNPs demonstrated 45.76% inhibition against P. aeruginosa at 1024 μg/mL and 44.64% inhibition against S. aureus at 128 μg/mL. At sub-MIC levels, EA-AuNPs significantly inhibited biofilm formation and virulence factors, including the motility of P. aeruginosa and staphyloxanthin synthesis in S. aureus. The RT-PCR analysis revealed the downregulation of key genes involved in biofilm formation and virulence in P. aeruginosa and S. aureus. Conclusions: These findings highlight the potential of E. bicyclis solvent-soluble extracts and EA-AuNPs as effective antibacterial, antibiofilm, and antivirulence agents, with significant application potential in the pharmaceutical and food industries. To the best of our knowledge, this is the first report of antibiofilm activity against both Gram-positive and Gram-negative bacteria using EA-AuNPs. Full article
(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)
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