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Antibiotics
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Antimicrobial Activity of Secondary Metabolites Produced in Nature
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Antimicrobial Activity of Secondary Metabolites Produced in Nature

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

Deadline for manuscript submissions: 31 August 2025 | Viewed by 18390

Special Issue Editors

Dr. Dragana Božić

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Guest Editor
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
Interests: antimicrobial resistance; biofilm; multi-resistant bacteria; methicillin-resistant staphylococcus aureus; antibiotics; natural and synthetic antimicrobial compounds; plant extracts and essential oils; chalcones; anticancer activity; anti-inflammatory activity; cytotoxicity assays; in vivo animal models of autoimmune diseases, sepsis, and inflammation; one health; microbiological quality control of medicines; GMP
Special Issues, Collections and Topics in MDPI journals
Dr. Mirjana D. Marčetić

E-Mail Website
Guest Editor
Department of Pharmacognosy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
Interests: bioactive phytochemicals; essential oils; plant extracts; phytochemistry; phytotherapy; composition, variability, and chemotaxonomic significance of essential oils; biological activity of herbal drugs; polyphenols; flavonoids; ethnopharmacology; antimicrobial activity; functional food

Special Issue Information

Dear Colleagues,

Antimicrobial resistance (AMR) is a growing global burden that results in increased morbidity, mortality, and healthcare costs. According to the World Health Organization, AMR leads to an estimated 700,000 deaths worldwide each year, and this number is expected to rise to 10 million deaths per year by 2050 if action is not taken. Such a complex problem requires a multifaceted approach involving not only better antibiotic stewardship and improved infection prevention and control, but also the development of novel antimicrobial agents.

Secondary metabolites are very potent organic compounds synthesized by plants, fungi, and bacteria as a means of defense against predators, competitors, or pathogens. Some examples of secondary metabolites from nature include alkaloids, flavonoids, terpenoids, and phenolic compounds, which have a wide range of biological activities, such as antimicrobial, antifungal, antiviral, antiprotozoal, antioxidant, anticancer, and anti-inflammatory properties. These compounds have been used for centuries in traditional medicine and are also a rich source of new drug leads for the pharmaceutical industry. Many drugs used in modern medicine, such as artemisinin, morphine, codeine, and atropine are derived from plant secondary metabolites, others are very potent antibacterial agents derived from fungi, such as penicillin, or bacteria, such as streptomycin, nystatin, erythromycin, vancomycin, teicoplanin, etc.

The aim of this Special Issue is to bring together experts from different areas of microbiology, pharmacognosy, pharmacology, and medicinal chemistry to promote interdisciplinary collaborations and facilitate the translation of scientific discoveries into new therapies for patients, as well as for the veterinarian sector. Topics of interest include the antimicrobial effect of secondary metabolites on microorganisms; they are not limited only to the stasis of growth or cytocidal effect, and extend to the inhibition of microorganisms through modulation of virulence factors. We encourage original research articles (in vitro, in vivo, and in silico), case reports, observational studies, clinical trials, systematic reviews, meta-analyses, and perspectives that provide new insights into these topics, and that have the potential to impact the field.

Dr. Dragana Božić
Dr. Mirjana D. Marčetić
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 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.

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

  • antimicrobial resistance
  • multidrug-resistant pathogens
  • secondary metabolites
  • natural products
  • terpenes
  • phenolic compounds
  • polyketides
  • antimicrobial peptides
  • bacteriocins
  • bacterial/fungal toxins

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Published Papers (8 papers)

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Research

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18 pages, 3541 KiB  
Article
Antimicrobial Potential of Secalonic Acids from Arctic-Derived Penicillium chrysogenum INA 01369
by Yulia A. Roshka, Natalia N. Markelova, Sofia D. Mashkova, Kseniya V. Malysheva, Marina L. Georgieva, Igor B. Levshin, Vladimir I. Polshakov, Alexander M. Arutyunian, Alexey S. Vasilchenko and Vera S. Sadykova
Antibiotics 2025, 14(1), 88; https://doi.org/10.3390/antibiotics14010088 - 14 Jan 2025
Viewed by 618
Abstract
In this study, two compounds have been isolated from the Arctic-derived fungus Penicillium chrysogenum INA 13460. Structural elucidation, performed using 2D NMR and HR-ESIMS data, has identified the compounds as stereoisomers of secalonic acids, dimeric tetrahydroxanthones. The absolute configurations of these stereoisomers have [...] Read more.
In this study, two compounds have been isolated from the Arctic-derived fungus Penicillium chrysogenum INA 13460. Structural elucidation, performed using 2D NMR and HR-ESIMS data, has identified the compounds as stereoisomers of secalonic acids, dimeric tetrahydroxanthones. The absolute configurations of these stereoisomers have been determined through conformational NMR analysis and circular dichroism spectroscopy. The antimicrobial activity of secalonic acids D and F has been evaluated against a diverse range of microorganisms, including Gram-positive multidrug-resistant Staphylococcus aureus, Gram-negative Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, the phytopathogen Pectobacterium carotovorum VKM-B1247, and the fungi Fusarium oxysporum VKPM F 890, Aspergillus fumigatus VKM F-37, and A. niger ATCC 16404. Genomic and chemical analyses further support P. chrysogenum INA 13460 as a promising natural source for antimicrobial drug discovery and biological control applications. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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17 pages, 1368 KiB  
Article
Embleporicin: A Novel Class I Lanthipeptide from the Actinobacteria Embleya sp. NF3
by Dora Onely Roblero-Mejía, Carlos García-Ausencio, Romina Rodríguez-Sanoja, Fernando Guzmán-Chávez and Sergio Sánchez
Antibiotics 2024, 13(12), 1179; https://doi.org/10.3390/antibiotics13121179 - 5 Dec 2024
Viewed by 870
Abstract
Genome mining has emerged as a revolutionary tool for discovering new ribosomally synthesized and post-translationally modified peptides (RiPPs) in various genomes. Recently, these approaches have been used to detect and explore unique environments as sources of RiPP-producing microorganisms, particularly focusing on endophytic microorganisms [...] Read more.
Genome mining has emerged as a revolutionary tool for discovering new ribosomally synthesized and post-translationally modified peptides (RiPPs) in various genomes. Recently, these approaches have been used to detect and explore unique environments as sources of RiPP-producing microorganisms, particularly focusing on endophytic microorganisms found in medicinal plants. Some endophytic actinobacteria, especially strains of Streptomyces, are notable examples of peptide producers, as specific biosynthetic clusters encode them. To uncover the genetic potential of these organisms, we analyzed the genome of the endophytic actinobacterium Embleya sp. NF3 using genome mining and bioinformatics tools. Our analysis led to the identification of a putative class I lanthipeptide. We cloned the core biosynthetic genes of this putative lanthipeptide, named embleporicin, and expressed them in vitro using a cell-free protein system (CFPS). The resulting product demonstrated antimicrobial activity against Micrococcus luteus ATCC 9341. This represents the first RiPP reported in the genus Embleya and the first actinobacterial lanthipeptide produced through cell-free technology. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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14 pages, 1205 KiB  
Article
Clinical Evidence on Expansion of Essential Oil-Based Formulation’s Pharmacological Activity in Bovine Mastitis Treatment: Antifungal Potential as Added Value
by Dragana Tomanić, Dragana D. Božić, Nebojša Kladar, Marko Samardžija, Jelena Apić, Jovan Baljak and Zorana Kovačević
Antibiotics 2024, 13(7), 575; https://doi.org/10.3390/antibiotics13070575 - 22 Jun 2024
Viewed by 1887
Abstract
Bovine mastitis, as a significant and prevalent health problem in dairy herds, is primarily attributed to bacterial infections. Yeasts, although considered relatively rare causative agents, have also been associated with mastitis in dairy cattle. Current mastitis treatment predominantly relies on antibiotics, with limited [...] Read more.
Bovine mastitis, as a significant and prevalent health problem in dairy herds, is primarily attributed to bacterial infections. Yeasts, although considered relatively rare causative agents, have also been associated with mastitis in dairy cattle. Current mastitis treatment predominantly relies on antibiotics, with limited emphasis on antifungal treatment. However, mycotic mastitis is challenging to treat, since these fungi are often resistant to antibiotics and may even utilize them for energy. In the current research, the in vivo antimicrobial activity of the essential oil-based formulation (Phyto-Bomat), as a possible alternative mastitis treatment associated with yeasts, was studied. This study involved a total of 68 animals from two dairy farms with diagnosed mastitis, and three treatment groups were established: conventional antibiotic treatment, Phyto-Bomat treatment, and the combination of both. The findings suggest significant variations in the presence of Candida samples based on the treatment administered, and the most significant difference was noted in cows treated with the combination (Phyto-Bomat and antibiotics). Yet, it is important to note that the results reveal that, regardless of the treatment type, there are statistically significant differences in the presence of Candida samples across the examined time points. These results aim to provide valuable insights into the potential of EOs as an alternative therapy in bovine mastitis, specifically targeting yeasts. Such findings could offer new strategies in the mycotic mastitis control and reducing the occurrence of secondary infections following antibiotic treatment. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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16 pages, 1248 KiB  
Article
Antibacterial Activities of Phenolic Compounds in Miang Extract: Growth Inhibition and Change in Protein Expression of Extensively Drug-Resistant Klebsiella pneumoniae
by Pannita Anek, Sutita Kumpangcum, Sittiruk Roytrakul, Chartchai Khanongnuch, Chalermpong Saenjum and Kulwadee Phannachet
Antibiotics 2024, 13(6), 536; https://doi.org/10.3390/antibiotics13060536 - 9 Jun 2024
Cited by 1 | Viewed by 1669
Abstract
The rising incidence of extensively drug-resistant (XDR) Klebsiella pneumoniae, including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. Miang, known as chewing tea, is produced from Camellia sinensis var. assamica or Assam tea leaves fermentation. Previous studies [...] Read more.
The rising incidence of extensively drug-resistant (XDR) Klebsiella pneumoniae, including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. Miang, known as chewing tea, is produced from Camellia sinensis var. assamica or Assam tea leaves fermentation. Previous studies revealed that the extract of Miang contains various phenolic and flavonoid compounds with numerous biological activities including antibacterial activity. However, the antibacterial activity of Miang against XDR bacteria especially colistin-resistant strains had not been investigated. In this study, the compositions of phenolic and flavonoid compounds in fresh, steamed, and fermented Assam tea leaves were examined by HPLC, and their antibacterial activities were evaluated by the determination of the MIC and MBC. Pyrogallol was detected only in the extract from Miang and showed the highest activities with an MIC of 0.25 mg/mL and an MBC of 0.25–0.5 mg/mL against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli ATCC 25922, colistin-resistant E. coli, and colistin-resistant K. pneumoniae. The effects on morphology and proteomic changes in K. pneumoniae NH54 treated with Miang extract were characterized by SEM and label-free quantitative shotgun proteomics analysis. The results revealed that Miang extract caused the decrease in bacterial cell wall integrity and cell lysis. The up- and downregulated expression with approximately a 2 to >5-fold change in proteins involved in peptidoglycan synthesis and outer membrane, carbohydrate, and amino acid metabolism were identified. These findings suggested that Miang containing pyrogallol and other secondary metabolites from fermentation has potential as an alternative candidate with an antibacterial agent or natural active pharmaceutical ingredient against XDR bacteria including colistin-resistant bacteria. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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20 pages, 4036 KiB  
Article
Isolation, Characterization of Pyraclostrobin Derived from Soil Actinomycete Streptomyces sp. HSN-01 and Its Antimicrobial and Anticancer Activity
by Halaswamy Hire Math, Sreenivasa Nayaka, Muthuraj Rudrappa, Raju Suresh Kumar, Abdulrahman I. Almansour, Karthikeyan Perumal and Girish Babu Kantli
Antibiotics 2023, 12(7), 1211; https://doi.org/10.3390/antibiotics12071211 - 20 Jul 2023
Cited by 5 | Viewed by 2401
Abstract
The present study demonstrated the isolation, characterization, and antimicrobial and anticancer activity of active metabolite produced from mining-soil-derived actinomycetes. Among the 21 actinomycete isolates, the isolate HSN-01 exhibited significant antimicrobial activity in primary screening and was identified as Streptomyces sp. through 16S rRNA [...] Read more.
The present study demonstrated the isolation, characterization, and antimicrobial and anticancer activity of active metabolite produced from mining-soil-derived actinomycetes. Among the 21 actinomycete isolates, the isolate HSN-01 exhibited significant antimicrobial activity in primary screening and was identified as Streptomyces sp. through 16S rRNA gene sequencing. The active metabolite was separated, purified, and confirmed through UV–Vis spectroscopy, FTIR, HR-ESI-MS, and NMR analysis and identified as pyraclostrobin. Further, the active metabolite pyraclostrobin was tested for antimicrobial and anticancer activity against the hepatocellular carcinoma (HepG2) cell line. The metabolite exhibited maximum antimicrobial potential with 17.0, 13.33, 17.66, 15.66, 14.66, and 14.0 mm of inhibition against B. cereus, S. aureus, E. coli, P. aeruginosa, S. flexneri, and C. glabrata. The active metabolite exhibited dose-dependent anticancer potential against the hepatocellular carcinoma (HepG2) cell line with the IC50 56.76 µg/mL. This study suggests that Streptomyces sp. HSN-01 is an excellent source of active secondary metabolites with various biological activities. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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Review

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23 pages, 1127 KiB  
Review
Evaluating the Efficacy of Secondary Metabolites in Antibiotic-Induced Dysbiosis: A Narrative Review of Preclinical Studies
by Corina Andrei, Anca Zanfirescu, Victor-Pierre Ormeneanu and Simona Negreș
Antibiotics 2025, 14(2), 138; https://doi.org/10.3390/antibiotics14020138 - 1 Feb 2025
Viewed by 202
Abstract
Background/Objectives: Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate [...] Read more.
Background/Objectives: Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy. Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included “gut microbiota”, “antibiotics”, and “secondary metabolites”. Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized. Results: Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation. Conclusions: Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
14 pages, 1958 KiB  
Review
Cinnamaldehyde in Focus: Antimicrobial Properties, Biosynthetic Pathway, and Industrial Applications
by Brandon Armando Jaramillo Jimenez, Fatima Awwad and Isabel Desgagné-Penix
Antibiotics 2024, 13(11), 1095; https://doi.org/10.3390/antibiotics13111095 - 18 Nov 2024
Viewed by 2157
Abstract
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural [...] Read more.
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural antimicrobial agent. Beyond its antimicrobial effects, TCA demonstrates promising antidiabetic and anti-inflammatory activities, making it a valuable compound in medicinal and cosmetic applications. Recent studies have highlighted its role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Furthermore, TCA has gained popularity in cosmetics due to its antimicrobial activity, antioxidant properties, and skin-friendly profile. This review provides a comprehensive overview of TCA’s antimicrobial potential, focusing on its mechanisms of action and its market and industrial applications. We also discuss the biosynthetic pathway of TCA, exploring both its natural production in cinnamon and advances in biotechnological production methods. As the demand for sustainable and natural antimicrobial agents grows, TCA emerges as a promising candidate for diverse applications. Finally, this review explores future directions for optimizing TCA production through metabolic engineering and synthetic biology approaches to meet industrial-scale demands. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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16 pages, 414 KiB  
Review
Alternatives to Antimicrobial Treatment in Bovine Mastitis Therapy: A Review
by Dragana Tomanić, Marko Samardžija and Zorana Kovačević
Antibiotics 2023, 12(4), 683; https://doi.org/10.3390/antibiotics12040683 - 30 Mar 2023
Cited by 22 | Viewed by 6601
Abstract
Despite preventive and therapeutic measures, mastitis continues to be the most prevalent health problem in dairy herds. Considering the risks associated with antibiotic therapy, such as compromised effectiveness due to the emergence of resistant bacteria, food safety issues, and environmental impact, an increasing [...] Read more.
Despite preventive and therapeutic measures, mastitis continues to be the most prevalent health problem in dairy herds. Considering the risks associated with antibiotic therapy, such as compromised effectiveness due to the emergence of resistant bacteria, food safety issues, and environmental impact, an increasing number of scientific studies have referred to the new therapeutic procedures that could serve as alternatives to conventional therapy. Therefore, the aim of this review was to provide insight into the currently available literature data in the investigation of non-antibiotic alternative approaches. In general, a vast number of in vitro and in vivo available data offer the comprehension of novel, effective, and safe agents with the potential to reduce the current use of antibiotics and increase animal productivity and environmental protection. Constant progress in this field could overcome treatment difficulties associated with bovine mastitis and considerable global pressure being applied on reducing antimicrobial therapy in animals. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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