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Antibiotics
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Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens
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Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 7141

Special Issue Editors

Dr. Andrés H. Uc-Cachón

E-Mail Website
Guest Editor
Unidad de Investigación Médica Yucatán, Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
Interests: medicinal plants as sources of antibacterial, antiprotozoal and antidiabetic agents; antimicrobial resistance of group ESKAPE-E; clinical and epidemiological study of bacterial diseases
Dr. Gloria María Molina-Salinas

E-Mail Website
Guest Editor
Unidad de Investigación Médica Yucatán, Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
Interests: clinical and molecular epidemiology of emerging, re-emerging, and healthcare-associated infections; development of new agents against multidrug-resistant mycobacterium tuberculosis and ESKAPE-E bacteria; ethnopharmacological study of Mayan medicinal plants for anti-infective properties
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pathogens, including bacteria, fungi, protozoa, helminths, and viruses, are responsible for millions of human fatalities. Coronavirus disease (COVID-19) and tuberculosis remain among the top 10 causes of global mortality. Furthermore, it is estimated that between now and 2050, more than 39 million individuals will die of antibiotic-resistant infections. Despite the availability of various drugs for infectious diseases, there is an urgent need for the development of novel therapies for emerging diseases, as well as for infections for which antibiotics are no longer effective due to antimicrobial resistance. Historically, plants have served as valuable sources of anti-infective agents, and numerous drugs used in contemporary medicine originate from botanical sources. The estimated number of plant species on Earth ranges from 250,000 to 500,000, many of which are utilized for medicinal purposes and are part of the healthcare systems in developing countries. In recent years, research has focused on the identification of plant extracts with activity against pathogens, with the objective of developing new phytodrugs. This Special Issue of Antibiotics presents the most recent research on plant extracts and their antimicrobial activities against emerging and drug-resistant pathogens.

Dr. Andrés H. Uc-Cachón
Dr. Gloria María Molina-Salinas
Guest Editors

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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 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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.

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Keywords

  • anti-infective agents
  • antimicrobial activity
  • human pathogens
  • medicinal plants
  • natural products
  • phytodrugs

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Published Papers (7 papers)

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Research

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18 pages, 849 KiB  
Article
Antimicrobial Activity of Greek Native Essential Oils Against Escherichia coli O157:H7 and Antibiotic Resistance Strains Harboring pNorm Plasmid, mecA, mcr-1 and blaOXA Genes
by Rafail Fokas, Zoi Anastopoulou and Apostolos Vantarakis
Antibiotics 2025, 14(8), 741; https://doi.org/10.3390/antibiotics14080741 - 24 Jul 2025
Viewed by 646
Abstract
Background/Objectives: The rapid emergence of antibiotic-resistant Escherichia coli in food and clinical environments necessitates new, clean-label antimicrobials. This study assessed eight Greek native essential oils—oregano, thyme, dittany, rosemary, peppermint, lavender, cistus and helichrysum—for activity against six genetically and phenotypically diverse E. coli strains [...] Read more.
Background/Objectives: The rapid emergence of antibiotic-resistant Escherichia coli in food and clinical environments necessitates new, clean-label antimicrobials. This study assessed eight Greek native essential oils—oregano, thyme, dittany, rosemary, peppermint, lavender, cistus and helichrysum—for activity against six genetically and phenotypically diverse E. coli strains (reference, pNorm, mecA, mcr-1, blaOXA and O157:H7). We aimed to identify oils with broad-spectrum efficacy and clarify the chemical constituents responsible. Methods: Disk-diffusion assays measured inhibition zones at dilutions from 50% to 1.56% (v/v). MIC and MBC values were determined by broth microdilution. GC–MS profiling identified dominant components, and Spearman rank-order correlations (ρ) linked composition to activity. Shapiro–Wilk tests (W = 0.706–0.913, p ≤ 0.002) indicated non-normal data, so strain comparisons used Kruskal–Wallis one-way ANOVA with Dunn’s post hoc and Bonferroni correction. Results: Oregano, thyme and dittany oils—rich in carvacrol and thymol—exhibited the strongest activity, with MIC/MBC ≤ 0.0625% (v/v) against all strains and inhibition zones > 25 mm at 50%. No strain-specific differences were detected (H = 0.30–3.85; p = 0.998–0.571; padj = 1.000). Spearman correlations confirmed that carvacrol and thymol content strongly predicted efficacy (ρ = 0.527–0.881, p < 0.001). Oils dominated by non-phenolic terpenes (rosemary, peppermint, lavender, cistus, helichrysum) showed minimal or no activity. Conclusions: Phenolic-rich EOs maintain potent, strain-independent antimicrobial effects—including against multidrug-resistant and O157:H7 strains—via a multi-target mode that overcomes classical resistance. Their low-dose efficacy and GRAS status support their use as clean-label food preservatives or adjuncts to antibiotics or bacteriophages to combat antimicrobial resistance. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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19 pages, 2063 KiB  
Article
Inhibition of the MRSA Biofilm Formation and Skin Antineoplastic Activity of Ethyl Acetate Roots and Aerial Parts Extracts from Geum urbanum L.
by Lyudmila Dimitrova, Maya M. Zaharieva, Lilia Tserovska, Milena Popova, Vassya Bankova and Hristo Najdenski
Antibiotics 2025, 14(7), 627; https://doi.org/10.3390/antibiotics14070627 - 20 Jun 2025
Viewed by 514
Abstract
Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the [...] Read more.
Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. Objectives: The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant Geum urbanum L. against methicillin-resistant S. aureus (MRSA) NBIMCC 8327. Methods: The effects of both extracts on the expression of biofilm-related genes, icaA and icaD, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. Results: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of icaA and icaD was upregulated, although the biofilm development was inhibited 72.4–90.5% by EtOAcAP and 18.9–20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC50 = 6.7–14.68 µg/mL) as compared to EtOAcR extract (IC50 = 8.73–23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). Conclusions: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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15 pages, 7806 KiB  
Article
Novel p-Hydroxybenzoic Acid Derivative Isolated from Bacopa procumbens and Its Antibacterial Activity
by Elizabeth Vargas-Anaya, Alejandro Zamilpa, Manasés González-Cortazar, Blanca Eda Domínguez-Mendoza, Ma. Dolores Pérez-García, Minerva Rosas Morales, Ada María Ríos Cortés and Valentin López Gayou
Antibiotics 2025, 14(6), 591; https://doi.org/10.3390/antibiotics14060591 - 7 Jun 2025
Viewed by 969
Abstract
Background/Objectives: Antimicrobial resistance represents a critical global health challenge that has been exacerbated by the significant decline in antibiotic development. Natural product-based drugs, particularly plant-derived phenolic compounds, offer promising alternatives to conventional antibiotics. This study aimed to isolate and characterize a novel phenolic [...] Read more.
Background/Objectives: Antimicrobial resistance represents a critical global health challenge that has been exacerbated by the significant decline in antibiotic development. Natural product-based drugs, particularly plant-derived phenolic compounds, offer promising alternatives to conventional antibiotics. This study aimed to isolate and characterize a novel phenolic compound from Bacopa procumbens, a Mexican perennial repent plant that is widespread in the Mexican valley and produces a variety of saponins, gastrodin derivatives, and phenolic acids, and to evaluate its antibacterial potential against clinically relevant pathogens. Methods: The hydroalcoholic extraction of B. procumbens was followed by liquid–liquid partitioning with ethyl acetate. The resulting fraction underwent chromatographic separation and purification. The structural elucidation of the isolated compound was performed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), mass spectrometry (MS-EI), and nuclear magnetic resonance (NMR) techniques. Antimicrobial activity was assessed via a microdilution assay against five bacterial strains, including drug-resistant Staphylococcus species and Gram-negative pathogens. Results: A novel phenolic compound, 5-(p-hydroxybenzoyl) shikimic acid (5pHSA), was isolated and characterized. The compound demonstrated moderate antibacterial activity against methicillin-resistant Staphylococcus haemolyticus and Escherichia coli (minimum inhibitory concentration (MIC) = 100 μg/mL) but showed limited efficacy against Staphylococcus aureus, MRSA, and Klebsiella pneumoniae (MIC > 100 μg/mL). Comparative analysis with the previously isolated compound ProcumGastrodin A revealed structure–activity relationships where the higher lipophilicity of PG-A was correlated with enhanced antimicrobial activity. Conclusions: This study establishes 5pHSA as a novel phenolic compound with moderate antibacterial properties. The findings highlight the importance of molecular polarity and structural complexity in determining antimicrobial efficacy, offering valuable insights into the development of phenolic, acid-based antimicrobial agents to address the growing challenge of antimicrobial resistance. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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26 pages, 13413 KiB  
Article
Use of Haloxylon scoparium Against Multidrug-Resistant Bacteria from Urinary Tract Infections
by Fouad Bahri, Abdelhadi Boussena, Antoni Szumny, Youcef Bahri, El-Mokhtar Bahri, Adam Figiel and Piotr Juszczyk
Antibiotics 2025, 14(5), 471; https://doi.org/10.3390/antibiotics14050471 - 6 May 2025
Viewed by 739
Abstract
Background: The emergence of multidrug-resistant bacteria in the urinary tract and the decrease in the efficacy of antibiotics prompted us to evaluate the antibacterial activity of the methanolic extract of the aerial parts of Haloxylon scoparium against six isolated (MDR) bacteria. Methods: Phenolic [...] Read more.
Background: The emergence of multidrug-resistant bacteria in the urinary tract and the decrease in the efficacy of antibiotics prompted us to evaluate the antibacterial activity of the methanolic extract of the aerial parts of Haloxylon scoparium against six isolated (MDR) bacteria. Methods: Phenolic compound profiling of the extract of interest was performed by HPLC-DAD. Acute oral toxicity was tested in vivo. The antibiotic susceptibility of the isolates was assessed against 23 antibiotics using the disk diffusion method. The identification of the isolates was performed by 16S rRNA gene sequencing. The antibacterial activity of the extract was assessed using agar well diffusion, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs) methods. Results: Phenolic compound profiling of the extract revealed that epicatechin (85%) was the major compound. The extract also showed no symptoms of toxicity, adverse effects, or mortality in mice at the recommended dose. Overall, the extract at 200 µg/mL was effective against all isolates. The zones of inhibition ranged from 9.25 to 19.5 mm. Gram-positive S. aureus bacteria recorded the highest inhibitory effect with 19.5 mm against the five Gram-negative bacteria (9.25–17.25 mm). The MIC of the extracts against clinical isolates ranged from 50 to 100 µg/mL. The extract was bactericidal against S. aureus, E. coli, E. ludwigii, and K. pneumoniae with an MBC of 100, 100, 200, and 200 µg/mL, respectively. Conclusions: The results conclude that the extract could be an effective source of antimicrobial agents for the treatment of urinary tract infections caused by MDR bacteria. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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Review

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25 pages, 1759 KiB  
Review
Harnessing the Potential of Antibacterial and Antibiofilm Phytochemicals in the Combat Against Superbugs: A One Health Perspective
by Suma Sarojini, Saranya Jayaram, Sandhya Kalathilparambil Santhosh, Pragyan Priyadarshini, Manikantan Pappuswamy and Balamuralikrishnan Balasubramanian
Antibiotics 2025, 14(7), 692; https://doi.org/10.3390/antibiotics14070692 - 9 Jul 2025
Viewed by 569
Abstract
The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in [...] Read more.
The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in the market. With the surge in the misuse of antibiotics, there was a drastic increase in the number of multidrug-resistant (MDR) and extensively drug-resistant bacterial strains, even to antibiotics like Methicillin and vancomycin, aggravating the healthcare scenario. The threat of MDR ESKAPE pathogens is particularly high in nosocomial infections, where biofilms formed by bacteria create a protective barrier that makes them highly resistant to antibiotics, complicating the treatment efforts. Scientists are looking at natural and sustainable solutions, as several studies have projected deaths contributed by drug-resistant bacteria to go beyond 50 million by 2050. Many plant-derived metabolites have shown excellent antibacterial and antibiofilm properties that can be tapped for combating superbugs. The present review explores the current status of various studies on antibacterial plant metabolites like alkaloids and flavonoids and their mechanisms in disrupting biofilms and killing bacteria by way of inhibiting key survival strategies of bacteria like motility, quorum-sensing, reactive oxygen species production, and adhesion. These mechanisms were found to be varied in Gram-positive, Gram-negative, and acid-fast bacteria like Mycobacterium tuberculosis, which will be discussed in detail. The successful tapping of the benefits of such plant-derived chemicals in combination with evolving techniques of nanotechnology and targeted drug delivery can go a long way in achieving the goal of One Health, which advocates the unity of multiple practices for the optimal health of people, animals, and the environment. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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52 pages, 8144 KiB  
Review
Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties
by Mulugeta Mulat, Riza Jane S. Banicod, Nazia Tabassum, Aqib Javaid, Abirami Karthikeyan, Geum-Jae Jeong, Young-Mog Kim, Won-Kyo Jung and Fazlurrahman Khan
Antibiotics 2025, 14(6), 555; https://doi.org/10.3390/antibiotics14060555 - 29 May 2025
Cited by 2 | Viewed by 884
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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23 pages, 6045 KiB  
Review
Comprehensive Overview of Antibacterial Drugs and Natural Antibacterial Compounds Found in Food Plants
by Sabine Berteina-Raboin
Antibiotics 2025, 14(2), 185; https://doi.org/10.3390/antibiotics14020185 - 11 Feb 2025
Cited by 1 | Viewed by 2036
Abstract
The aim of this review is to list the various natural sources of antimicrobials that are readily available. Indeed, many plant sources are known to have antibiotic properties, although it is not always clear which molecule is responsible for this activity. Many food [...] Read more.
The aim of this review is to list the various natural sources of antimicrobials that are readily available. Indeed, many plant sources are known to have antibiotic properties, although it is not always clear which molecule is responsible for this activity. Many food supplements also have this therapeutic indication. We propose here to take stock of the scientific knowledge attesting or not to these indications for some food sources. An overview of the various antibiotic drugs commercially available will be provided. A structural indication of the natural molecules present in various plants and reported to contribute to their antibiotic power will be given. The plants mentioned in this review, which does not claim to be exhaustive, are referenced for fighting Gram-positive and/or Gram-negative bacteria. It is difficult to attribute activity to just one of these natural molecules, as it is likely to result from synergy within the plant. Similarly, chitosan is mentioned for its fungistatic and bacteriostatic properties. In this case, this polymeric compound derived from the chitin of marine organisms is referenced for its antibiofilm activity. It seems that, in the face of growing antibiotic resistance, it makes sense to keep high-performance synthetic antibiotics on hand to treat the difficult pathologies that require them. On the other hand, for minor infections, the use of better-tolerated natural sources is certainly sufficient. To achieve this, we need to take stock of common plant sources, available as food products or dietary supplements, which are known to be active in this field. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)
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