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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 13259

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Special Issue Editors

Dr. Anca Zanfirescu

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Guest Editor

Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: AI in drug design; small-molecule therapeutics; drug target prediction; pharmacoinformatics
Special Issues, Collections and Topics in MDPI journals

Dr. Corina Andrei

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Guest Editor Assistant

Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: computational drug discovery; pharmacoinformatics; virtual screening
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global rise of antimicrobial resistance presents a critical challenge to public health, as antibiotics steadily lose their effectiveness against a growing number of resistant pathogens. This Special Issue calls for innovative solutions, and natural products have emerged as promising candidates for the development of novel antimicrobial agents.

We are delighted to announce this Special Issue, titled “Advanced Research on Antimicrobial Activity of Natural Products”, dedicated to showcasing groundbreaking advancements in this dynamic field. This Special Issue aims to highlight the discovery, characterization, and application of bioactive compounds derived from natural sources, with a focus on combating resistant strains and exploring innovative therapeutic strategies.

We warmly invite researchers to contribute original research articles and in-depth reviews. Areas of interest include, but are not limited to, the following:

Identification and isolation of novel antimicrobial compounds;
Mechanistic studies and biosynthetic pathways;
Synergistic effects with existing antibiotics;
Exploration of traditional medicinal plants and their derivatives.

This Special Issue offers a platform for presenting research that bridges the gap between natural product discovery and the pressing need for effective anti-infective solutions. Contributions that emphasize the transformative potential of natural ingredients in addressing the limitations of current antibiotic therapies are especially encouraged. We look forward to your valuable contributions.

Dr. Anca Zanfirescu
Guest Editor

Dr. Corina Andrei
Guest Editor Assistant

Manuscript Submission Information

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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. Microorganisms 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 2700 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
antimicrobial activity
pathogens
infectious disorders
natural products
anti-infective agents

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Published Papers (8 papers)

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Research

14 pages, 2069 KB

Open AccessArticle

In Situ Gel Containing Lippia sidoides Cham. Essential Oil for Microbial Control in the Oral Cavity

by Maria Vitoria Oliveira Dantas, Quemuel Pereira da Silva, Alexandre Almeida Júnior, João Vitor Souto Araújo Queiroz, José Filipe Bacalhau Rodrigues, Rosana Araújo Rosendo, Marcus Vinicius Lia Fook, Paulo Rogério Ferreti Bonan, Francisco Humberto Xavier Júnior and Fábio Correia Sampaio

Microorganisms 2025, 13(11), 2585; https://doi.org/10.3390/microorganisms13112585 - 13 Nov 2025

Viewed by 579

Abstract

Surgical site infections in oral and maxillofacial interventions are often exacerbated by biofilm formation, and current antimicrobial treatments are hampered by issues such as resistance and adverse effects. This article aimed to develop, characterize, and evaluate the antimicrobial activity of Lippia sidoides Cham. essential oil (LSEO) gel composed of poloxamer (P) and chitosan (C). Gas chromatography–mass spectrometry (GC-MS) analysis identified thymol as the major component of LSEO (71.04%). In situ P-gels containing LSEO (0.25–1.0%) were produced with and without C. The addition of C resulted in gels with nanometric particle sizes (263.8 ± 231 nm; PDI 0.39 ± 0.17) and a positive zeta potential (+4.81 ± 1.97 a + 8.19 ± 0.51 mV), exhibiting pseudoplastic behavior in rheological analysis. The sol–gel transition temperature (Tsol–gel) was found to be between 20 and 28 °C, with a transition time at 37 °C ranging from 18.76 ± 1.24 s to 46.46 ± 8.89 s. LSEO showed MIC values of 256, 128, and 128 µg/mL against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively, while in situ LSEO gels presented MIC values above 5 µg/mL for all tested strains. Therefore, the developed gel containing LSEO showed promising application in dentistry, offering a potential new treatment perspective for surgical site infections in oral and maxillofacial surgery. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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19 pages, 1270 KB

Open AccessArticle

Synergistic Interactions Between Natural Phenolic Compounds and Antibiotics Against Multidrug-Resistant K. pneumoniae: A Pooled Analysis of 216 In Vitro Tests

by Victor-Pierre Ormeneanu, Corina Andrei, Anca Zanfirescu, Ciprian Pușcașu, Octavian Tudorel Olaru and Simona Negreș

Microorganisms 2025, 13(11), 2497; https://doi.org/10.3390/microorganisms13112497 - 30 Oct 2025

Viewed by 667

Abstract

The rapid global emergence of multidrug-resistant (MDR) Klebsiella pneumoniae threatens public health, as treatment options remain limited and resistance to last-line antibiotics is rising. Natural phenolic compounds emerge as promising adjuvants to restore antibiotic activity. This study pooled data from 216 in vitro assays evaluating interactions between phenolic compounds and conventional antibiotics against MDR K. pneumoniae. Fractional inhibitory concentration index (FICI) values were analyzed at the individual-test level, and structure–activity relationships were explored using a binary chemotype flagging approach. Overall, synergy was highly context-dependent, varying by both antibiotic class and phenolic chemotype. Polymyxin B combined with resveratrol demonstrated the most consistent and robust synergy (median FICI = 0.25, synergy rate = 96.2%), with no antagonism observed. For carbapenems, meropenem showed strong synergy when paired with flavonoids containing catechol or gallol motifs (e.g., quercetin, kaempferol), whereas curcumin exhibited inconsistent or antagonistic effects. Variability analysis revealed that combinations with low dispersion, such as polymyxin B + resveratrol, offer greater translational potential than high-variability pairs. These findings highlight the structural determinants of synergy and support further preclinical evaluation of select phenolic compounds as adjuvants to conventional antibiotics in the fight against MDR K. pneumoniae. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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15 pages, 2402 KB

Open AccessArticle

Inhibition of Clostridium perfringens Spore Germination by the Synergistic Effects of the Natural Products Chitosan and Nisin

by Rabiaa S. Alhabeeb, Roua Almatrafi, Saeed S. Banawas, Maryam Alnoman and Mahfuzur R. Sarker

Microorganisms 2025, 13(9), 2116; https://doi.org/10.3390/microorganisms13092116 - 10 Sep 2025

Viewed by 842

Abstract

Clostridium perfringens is a spore-forming bacterium that causes food poisoning. Given the high heat resistance of its spores, natural antimicrobial agents are considered as alternatives to thermal processing strategies to inactivate or eliminate such spores from food products. A high chitosan concentration (0.2%) can effectively inhibit the growth of C. perfringens spores in cooked chicken meat, whereas nisin cannot (even at concentrations four times higher than those permitted: 250 μM). However, nisin is an effective inhibitor when in combination with other preservatives. Therefore, we evaluated the inhibitory effects of a chitosan–nisin combination on the germination, outgrowth, and vegetative growth of C. perfringens spores in laboratory medium and chicken meat. Among many tested concentration combinations, a 0.025% chitosan and 0.075% nisin mixture was found to be the most effective for inhibiting spore germination and outgrowth in laboratory medium. Furthermore, a mixture of chitosan–nisin, at 0.025% each, blocked the vegetative growth of C. perfringens spores. However, four-times higher concentrations of chitosan–nisin (0.1% each) were required to effectively inhibit C. perfringens spore germination in chicken meat. Collectively, our results suggest that the combination of chitosan and nisin can be considered as an alternative approach to control C. perfringens spore germination in meat products. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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28 pages, 2282 KB

Open AccessArticle

From Hue to Health: Exploring the Therapeutic Potential of Plant-Pigment-Enriched Extracts

by Azza SalahEldin El-Demerdash, Amira E. Sehim, Abeer Altamimi, Hanan Henidi, Yasmin Mahran and Ghada E. Dawwam

Microorganisms 2025, 13(8), 1818; https://doi.org/10.3390/microorganisms13081818 - 4 Aug 2025

Cited by 2 | Viewed by 1218

Abstract

The escalating global challenges of antimicrobial resistance (AMR) and cancer necessitate innovative therapeutic solutions from natural sources. This study investigated the multifaceted therapeutic potential of pigment-enriched plant extracts. We screened diverse plant extracts for antimicrobial and antibiofilm activity against multidrug-resistant bacteria and fungi. Hibiscus sabdariffa emerged as the most promising, demonstrating potent broad-spectrum antimicrobial and significant antibiofilm activity. Sub-inhibitory concentrations of H. sabdariffa robustly downregulated essential bacterial virulence genes and suppressed aflatoxin gene expression. Comprehensive chemical profiling via HPLC identified major anthocyanin glucosides, while GC-MS revealed diverse non-pigment bioactive compounds, including fatty acids and alcohols. Molecular docking suggested favorable interactions of key identified compounds (Cyanidin-3-O-glucoside and 1-Deoxy-d-arabitol) with E. coli outer membrane protein A (OmpA), indicating potential antiadhesive and antimicrobial mechanisms. Furthermore, H. sabdariffa exhibited selective cytotoxicity against MCF-7 breast cancer cells. These findings establish H. sabdariffa pigment-enriched extract as a highly promising, multi-functional source of novel therapeutics, highlighting its potential for simultaneously addressing drug resistance and cancer challenges through an integrated chemical, biological, and computational approach. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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18 pages, 2887 KB

Open AccessArticle

Effects of Natural Ingredient Xanthohumol on the Intestinal Microbiota, Metabolic Profiles and Disease Resistance to Streptococcus agalactiae in Tilapia Oreochromis niloticus

by Aiguo Huang, Yanqin Wei, Jialong Huang, Songlin Luo, Tingyu Wei, Jing Guo, Fali Zhang and Yinghui Wang

Microorganisms 2025, 13(7), 1699; https://doi.org/10.3390/microorganisms13071699 - 20 Jul 2025

Viewed by 866

Abstract

Streptococcus agalactiae (SA) is a severe prevalent pathogen, resulting in high morbidity and mortality in the global tilapia industry. With increasing bacterial resistance to antibiotics, alternative strategies are urgently needed. This study aims to investigate the antibacterial activity and the underlying mechanisms of the natural product xanthohumol (XN) against SA infection in tilapia (Oreochromis niloticus). The results showed that XN could significantly reduce the bacterial loads of SA in different tissues (liver, spleen and brain) after treatment with different tested concentrations of XN (12.5, 25.0 and 50.0 mg/kg). Moreover, XN could improve the survival rate of SA-infected tilapia. 16S rRNA gene sequencing demonstrated that the alpha-diversity index (Chao1 and Shannon_e) was significantly increased in the XN-treated group (MX group) compared to the SA-infected group (CG group) (p < 0.05), and the Simpson diversity index significantly decreased. The Bray–Curtis similarity analysis of non-metric multidimensional scaling (NMDS) and principal coordinate analysis (PCA) showed that there were significant differences in microbial composition among groups. At the phylum level, the relative abundance of the phyla Actinobacteria, Proteobacteria and Bacteroidetes decreased in the MX group compared to the CG group, while the relative abundance of the phyla Fusobacteria, Firmicutes and Verrucomicrobia increased. Differences were also observed at the genus level; the relative abundance of Mycobacterium decreased in the MX group, but the abundance of Cetobacterium and Clostridium_sensu_stricto_1 increased. Metabolomics analysis revealed that XN changed the metabolic profile of the liver and significantly enriched aspartate metabolism, glycine and serine metabolism, phosphatidylcholine biosynthesis, arginine and proline metabolism, glutamate metabolism, urea cycle, purine metabolism, methionine metabolism, betaine metabolism, and carnitine synthesis. Correlation analysis indicated an association between the intestinal microbiota and metabolites. In conclusion, XN may be a potential drug for the prevention and treatment of SA infection in tilapia, and its mechanism of action may be related to the regulation of the intestinal microbiota and liver metabolism. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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18 pages, 869 KB

Open AccessArticle

Comparison of In Vitro Methods for Assaying the Antibacterial Activity of a Mix of Natural Essential Oils Against Zoonotic Bacteria

by Karine Fayolle, Claire Girard, Pauline Lasfargues, Sahar Koteich and Sylvain Kerros

Microorganisms 2025, 13(5), 1125; https://doi.org/10.3390/microorganisms13051125 - 14 May 2025

Cited by 1 | Viewed by 2106

Abstract

With the increasing occurrence of bacterial resistance, it is now essential to look for new alternatives to protect the curative utilization of antibiotics within the One Health concept. Here, we adapt and optimize a broth microdilution method and compare it against the broth macrodilution method for evaluating the antibacterial activity of a complex essential oils mix (EO mix) against four livestock pathogens: Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, and Staphylococcus aureus. Microdilution method performance (final volume well: 300 µL; inoculum: 1.0 × 10⁶ CFU/mL) was evaluated following CLSI recommendations, by comparing the MIC of each of the four strains with the MICs obtained with the macrodilution method (final volume tube: 2 mL; inoculum 1.0 × 10⁶ CFU/mL). Microdilution analysis was performed with an automated plate reader (Bioscreen C), and three bacterial growth parameters (OD max, lag phase, and growth rate) were calculated (DMFit curve-fitting software (v2.1; courtesy of the Institute of Food Research, Norwich, UK)). EO mix MICs were determined for E. coli, S. aureus, and B. cereus. Our results emphasize the importance of ensuring the accuracy of MIC results by performing three technical and three biological replicates, and combining OD max, lag phase, and growth rate to assess the impact of an EO mix at sub-MIC levels. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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19 pages, 1580 KB

Open AccessArticle

Fungistatic and Bactericidal Activity of Hydroalcoholic Extracts of Root of Jatropha dioica Sessé

by Lizeth Aguilar-Galaviz, Jorge Cadena-Iñiguez, Dalia Abigail García-Flores, Gerardo Loera-Alvarado, Diego Rivera-Escareño and María Azucena Ortega-Amaro

Microorganisms 2025, 13(5), 1027; https://doi.org/10.3390/microorganisms13051027 - 29 Apr 2025

Cited by 1 | Viewed by 1056

Abstract

Jatropha dioica Sessé (JD) is a plant from arid and semiarid zones of Mexico related to local therapeutic uses and possible use in food and agriculture as a control agent of pest organisms that helps to reduce impacts on the environment, human health and resistance by phytopathogens. In vitro bactericidal activity was evaluated with the well diffusion method in doses of 1000, 2500, 5000, 7500, 10,000 and 20,000 µg mL⁻¹, and fungistatic activity was evaluated with the agar dilution method (500, 1000, 1500, 2000 and 4000 µg mL⁻¹) in Pseudomonas syringae, Botrytis cinerea and Fusarium oxysporum using hydroalcoholic extracts of J. dioica root in a completely randomized design with five replications. Total phenol and flavonoid contents were recorded by the Folin–Ciocalteu and aluminum chloride methods. Ethanol and methanol extracts showed fungistatic activity on B. cinerea, inhibiting from 42.27 ± 1.09 to 46.68 ± 0.98 mg mL⁻¹, with an IC₅₀ of 5.04 mg mL⁻¹, with no differences by solvent type. In F. oxysporum, inhibition ranged from 14.77 ± 1.08 to 29.19 ± 0.89 mg mL⁻¹, and the methanol extract was more efficient, generating a stress response to the ethanol extract. The bactericidal activity on P. syringae recorded inhibition zones of 17.66 ± 0.33 and 16.66 ± 0.33 mg mL⁻¹, with ethanol being more efficient. The phenol content ranged from 8.92 ± 0.25 to 12.10 ± 0.34 mg EAG g⁻¹ and flavonoid content ranged from 20.49 ± 0.33 to 28.21 ± 0.73 mg QE g⁻¹ of sample dry weight. The results highlight the biological activity of J. dioica as an alternative to biopesticides that minimize agrochemical applications and generate pathogen resistance. These advances contribute to the revaluation and conservation of the species. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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21 pages, 654 KB

Open AccessArticle

Antibacterial Effects of Bulgarian Oregano and Thyme Essential Oils Alone and in Combination with Antibiotics Against Klebsiella pneumoniae and Pseudomonas aeruginosa

by Silviya Mihaylova, Antoaneta Tsvetkova, Sylvia Stamova, Neli Ermenlieva, Gabriela Tsankova, Emiliya Georgieva, Katya Peycheva, Veselina Panayotova and Yulian Voynikov

Microorganisms 2025, 13(4), 843; https://doi.org/10.3390/microorganisms13040843 - 7 Apr 2025

Cited by 2 | Viewed by 5331

Abstract

Antimicrobial resistance (AMR) poses a global health threat, with multidrug-resistant (MDR) Klebsiella pneumoniae and Pseudomonas aeruginosa contributing to the burden, especially in Bulgaria. This study investigates recent resistance trends of these pathogens in Bulgaria and evaluates the antibacterial effects of commercially available oregano (Origanum vulgare) and thyme (Thymus vulgaris) essential oils (EOs), both alone and in combination with conventional antibiotics. The chemical composition of the EOs was analyzed using gas chromatography–mass spectrometry (GC-MS), revealing carvacrol (84.2%) as the main component in oregano EO and thymol (45.74%) in thyme EO. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the EOs were determined using the serial dilution method. Oregano EO exhibited lower MIC and MBC values (0.039–1.250%) compared to thyme EO (0.156–5.000%) against both pathogens. The disk diffusion assay showed that oregano EO exhibits more potent antibacterial effects than thyme EO in Klebsiella pneumoniae and Pseudomonas aeruginosa strains. The findings highlight the potential of EOs as adjunctive therapies to enhance the efficacy of conventional antibiotics against MDR Klebsiella pneumoniae and Pseudomonas aeruginosa strains in Bulgaria. Full article

(This article belongs to the Special Issue Advanced Research on Antimicrobial Activity of Natural Products)

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