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26 pages, 14596 KB  
Article
Callus Induction in Ludwigia octovalvis: Chemical Characterization and Potential Pharmacological Applications
by Stephany Abigail Tadeo-Cuenca, Silvia Marquina-Bahena, Elizabeth Negrete-León, Juan José Acevedo-Fernández, María Crystal Columba-Palomares, Araceli Guerrero-Alonso, Francisco Cruz-Sosa and Mariana Sánchez-Ramos
Plants 2026, 15(17), 2590; https://doi.org/10.3390/plants15172590 - 25 Aug 2026
Abstract
Antimicrobial resistance has intensified the search for novel antimicrobial and wound-healing agents. Ludwigia octovalvis (Jacq.) P.H. Raven is traditionally used to treat infections, inflammation, and skin disorders, although its in vitro biotechnological potential remains largely unexplored. This study reports the first successful establishment [...] Read more.
Antimicrobial resistance has intensified the search for novel antimicrobial and wound-healing agents. Ludwigia octovalvis (Jacq.) P.H. Raven is traditionally used to treat infections, inflammation, and skin disorders, although its in vitro biotechnological potential remains largely unexplored. This study reports the first successful establishment of L. octovalvis callus cultures, their characterization by gas chromatography-mass spectrometry (GC-MS), and the evaluation of their antimicrobial and wound-healing activities. Friable calluses were induced from leaf and node explants of axenic seedlings using combinations of 6-benzylaminopurine (BAP), kinetin (KIN), 2,4-dichlorophenoxyacetic acid (2,4-D), and α-naphthaleneacetic acid (NAA). Optimal callus induction was achieved in leaf explants cultured on full-strength Murashige and Skoog (MS) medium supplemented with BAP (4.44 µM) and 2,4-D (0.45 µM). After six months of subculture, the calluses showed morphological uniformity and stable biomass production. Growth kinetics followed a specific growth rate of 0.047 d−1 and a doubling time of 14.54 days. GC-MS analysis identified fatty acids and phytosterols as the main components. The ethyl acetate extract significantly improved wound healing in vivo, while the methanolic extract exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). These findings demonstrate that L. octovalvis callus cultures constitute a sustainable source of bioactive compounds with promising therapeutic potential. Full article
(This article belongs to the Special Issue Plant Specialized Metabolites)
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20 pages, 2132 KB  
Article
Discovery of a Novel Benzothiophene Inhibitor of Penicillin-Binding Protein 2 with Potent Gram-Positive Activity
by Monica A. Stefaniak, Vijay Singh Gondil, Jingdong Yang, Adil Omar, Allen G. Oliver, Ansley M. Nemeth, Roberta J. Melander, Mayland Chang, Paul M. Dunman and Christian Melander
Antibiotics 2026, 15(9), 826; https://doi.org/10.3390/antibiotics15090826 - 25 Aug 2026
Abstract
Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for new antibacterial agents. Here, we report the identification and evaluation of a novel Gram-positive selective antibacterial: NDM-552. Methods: Antibacterial activity was determined by broth microdilution against a panel of [...] Read more.
Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for new antibacterial agents. Here, we report the identification and evaluation of a novel Gram-positive selective antibacterial: NDM-552. Methods: Antibacterial activity was determined by broth microdilution against a panel of Gram-positive and Gram-negative pathogens. Mechanistic studies included BOCILLIN-FL competition assays, microscale thermophoresis (MST), and antibiotic interaction with oxacillin and moenomycin. Additionally, time–kill analyses, frequency-of-resistance measurements, cytotoxicity assays, plasma stability studies, and a murine wound infection model were performed to characterize NDM-552. Results: NDM-552 exhibits activity against Gram-positive pathogens including S. aureus, Enterococcus faecium, and Staphylococcus epidermidis, with minimum inhibitory concentrations (MICs) of 1–2 µg/mL. NDM-552 displays no activity against Gram-negative bacteria. NDM-552 displays bacteriostatic activity against MRSA and additive interactions with oxacillin and moenomycin. The frequency of resistance in MRSA is low (2.39 × 10−9). BOCILLIN-FL competition assays and MST binding analysis identify the essential penicillin-binding protein 2 (PBP2) as the potential target of NDM-552. NDM-552 demonstrates acceptable cytotoxicity, favorable plasma stability, and reduces bacterial burden in a murine wound infection model. Conclusions: NDM-552 is a potent Gram-positive selective antibacterial agent that potentially targets PBP2-associated cell wall biosynthesis and exhibits in vivo efficacy against MRSA. Findings establish NDM-552 as a promising scaffold for the development of new antibacterial agents. Full article
(This article belongs to the Special Issue Antimicrobials Agents: Latest Advances and Prospects, 2nd Edition)
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18 pages, 13584 KB  
Article
Novel Lytic Agrobacterium Bacteriophage Miki Representing a New Genus
by Anna D. Tokmakova, Anna A. Lukianova, Mikhail M. Shneider, Ilia A. Putilov, Ekaterina S. Elkina, Maria S. Filatova, Anna D. Burtseva, Konstantin M. Boyko, Yuliya V. Mikhailova, Andrey A. Shelenkov, Peter V. Evseev and Konstantin A. Miroshnikov
Viruses 2026, 18(9), 927; https://doi.org/10.3390/v18090927 - 22 Aug 2026
Viewed by 197
Abstract
Rhizogenic Agrobacterium (Rhizobium) spp. are causative agents of hairy root disease (HRD), a major threat to hydroponic crop production worldwide. The use of specific bacteriophages is considered a prospective approach to control the development of HRD in greenhouses. A combination of [...] Read more.
Rhizogenic Agrobacterium (Rhizobium) spp. are causative agents of hairy root disease (HRD), a major threat to hydroponic crop production worldwide. The use of specific bacteriophages is considered a prospective approach to control the development of HRD in greenhouses. A combination of diverse bacteriophages is a key step to overcome potential phage resistance in the pathogen. In this study, a novel lytic bacteriophage, named Miki, was identified and characterized for its antibacterial potential against a rhizogenic Agrobacterium sp. strain circulating in greenhouses in Central Russia. High-throughput sequencing revealed a 63,458 bp double-stranded DNA genome (G + C content 53%), with 117 predicted coding sequences, considering Miki as a lytic candidate phage for plant protection. Electron microscopy of phage Miki shows a morphology unusual for Agrobacterium phages, and phylogenetic analysis attributes it as a representative of a previously undescribed taxon at least at the genus level. The paper presents a detailed analysis of the genome and structural proteome of phage Miki, including in silico predictions and modeling of receptor-binding proteins, including central and proximal fibers resembling the adsorption apparatus of Escherichia phage T5. Full article
(This article belongs to the Special Issue Bacteriophage-Based Biocontrol in Agriculture, 3rd Edition)
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26 pages, 12863 KB  
Article
Exploring the Molecular Mechanism of Cinnamaldehyde Intervening in Ochratoxin A-Induced Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Comorbidity: An Integrated Approach Based on Network Pharmacology, Network Toxicology and Molecular Docking
by Mingli Shen, Qingping Shi, Shuang Gao, Beiyan Chen and Jieru Han
Pharmaceuticals 2026, 19(8), 1283; https://doi.org/10.3390/ph19081283 - 13 Aug 2026
Viewed by 250
Abstract
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it [...] Read more.
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 3rd Edition)
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19 pages, 2913 KB  
Review
Oral Cavity Antibacterial Discovery Pipeline Driven by Advanced Analytical Techniques
by Antonella Maria Aresta, Giada Stefania Signorile, Antonietta Clemente, Nicoletta De Vietro and Carlo Zambonin
Molecules 2026, 31(16), 2804; https://doi.org/10.3390/molecules31162804 - 12 Aug 2026
Viewed by 253
Abstract
The oral cavity represents an extremely complex and dynamic microbial ecosystem capable of rapidly adapting to antimicrobial stress. These characteristics make it a promising environment for the identification of novel bioactive molecules with therapeutic potential. At the same time, the increasing prevalence of [...] Read more.
The oral cavity represents an extremely complex and dynamic microbial ecosystem capable of rapidly adapting to antimicrobial stress. These characteristics make it a promising environment for the identification of novel bioactive molecules with therapeutic potential. At the same time, the increasing prevalence of resistant pathogens in dental and oral-maxillofacial infections highlights the limitations of current therapeutic strategies and the urgent need for new effective antibacterial agents. This review examines the central role of advanced analytical techniques, with particular emphasis on mass spectrometry, in the discovery and characterization of bioactive metabolites and biomarkers relevant to future antibacterial discovery and to the understanding of biological responses to pathogens or therapeutic interventions. It discusses how the integration of metabolomics approaches, imaging mass spectrometry, and bioinformatics platforms is transforming the antibacterial discovery process by accelerating the identification of active compounds and improving the understanding of microbial interactions within the oral cavity. Overall, this work provides an up-to-date overview of current knowledge regarding the oral microbiome as a source of bioactive molecules and biomarkers. It highlights how emerging analytical technologies are opening new perspectives for the development of innovative therapeutic strategies against resistant oral infections. Full article
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25 pages, 8513 KB  
Article
Antibacterial and Immunomodulatory Effects of Limosilactobacillus reuteri LMG P-27481 and Resveratrol Relevant for the Control of Upper Respiratory Tract Pathobionts
by Roberto Mattioli, Daniel Di Risola, Francesca Sivori, Ornella Franzese, Ilaria Genovese, Paola Mastromarino and Luciana Mosca
Microorganisms 2026, 14(8), 1771; https://doi.org/10.3390/microorganisms14081771 - 12 Aug 2026
Viewed by 251
Abstract
Although most upper respiratory tract infections (URTIs) have a viral etiology, antibiotics are widely prescribed, thus contributing substantially to antimicrobial resistance. This study investigated the potential beneficial effects of a novel strain, Limosilactobacillus reuteri LMG P-27481, against major URT pathobionts (Staphylococcus aureus [...] Read more.
Although most upper respiratory tract infections (URTIs) have a viral etiology, antibiotics are widely prescribed, thus contributing substantially to antimicrobial resistance. This study investigated the potential beneficial effects of a novel strain, Limosilactobacillus reuteri LMG P-27481, against major URT pathobionts (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) with the aim of reducing or delaying antibiotic use. Antibacterial and immunomodulatory activities were evaluated using L. reuteri alone or combined with resveratrol, a natural compound with antiviral and anti-inflammatory properties. Both agents inhibited pathogen growth, while their combination showed additive antibacterial activity, particularly against Gram-negative bacteria. Antioxidant assays demonstrated significant antioxidant capacity for both agents, with enhanced effects in combination in NBT and ABTS assays but antagonistic in ORAC. Immune mediators (IL-6, IL-8, IL-1β, TNF-α, IL-25, IL-33, CCL17, CCL22) were assessed in epidermal, epithelial, and macrophage cell lines, together with epidermal integrity markers (Filaggrin, Loricrin, Involucrin) in a 3D reconstructed human skin model (EpiDermFTTM). L. reuteri, resveratrol, and their combination exerted cell-specific effects in the different models, modulating cytokine expression and production, and barrier integrity. Our findings support the potential efficacy of oral L. reuteri LMG P-27481 plus resveratrol in URTIs. Full article
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29 pages, 27850 KB  
Article
Composite Hydrogel Loading Polysaccharides Derived from Coptis chinensis Franch. for Promoting Diabetic Wound Healing
by Menghan Li, Bin Zhang, Youyan Zeng, Yongxin Mao, Jinyi Zhang, Tingfang Zhao, Huanglin Huo, Huicong Zeng, Qian Zhou and Bo Li
Biomolecules 2026, 16(8), 1162; https://doi.org/10.3390/biom16081162 - 10 Aug 2026
Viewed by 201
Abstract
Efficient treatment of diabetic wounds (DW) remains a major clinical challenge worldwide owing to vascular insufficiency, multiple bacterial infections, and overactivation of pro-inflammatory M1 macrophages caused by hyperglycemia. The development of novel pharmaceutical agents with multiple biological functions is urgently needed. Coptis chinensis [...] Read more.
Efficient treatment of diabetic wounds (DW) remains a major clinical challenge worldwide owing to vascular insufficiency, multiple bacterial infections, and overactivation of pro-inflammatory M1 macrophages caused by hyperglycemia. The development of novel pharmaceutical agents with multiple biological functions is urgently needed. Coptis chinensis Franch. (CC) has been used to treat diabetes for thousands of years in China, but the curative effects and underlying mechanisms of CC in DW remain uncertain. Herein, a homogeneous heteropolysaccharide component, namely CCP, was isolated and purified from CC, which exhibited a molecular weight of 39,697 Da and was primarily composed of Glc, GalA, Ara, Gal, and Xyl. CCP has a light yellowish color and is distributed in a block shape with small surface granulations. In vitro experiments revealed that CCP dose-dependently mitigated high glucose-induced suppression of viability, migration, and tube formation in HUVECs. Meanwhile, CCP promotes the polarization of M1 macrophages toward the M2 phenotype to exert anti-inflammatory effects, while possessing certain antibacterial properties. In addition, a composite hydrogel system was successfully constructed by introducing sodium carboxymethyl cellulose and carbomer 940 for CCP delivery. The obtained hydrogels exhibited reasonable moisturizing, swelling, and drug release capacities, along with favorable rheological behaviors and certain antibacterial activity. More importantly, the in vivo wound healing model evaluation in diabetic rats demonstrated that CCP hydrogel dressings could effectively promote wound healing by reducing inflammation, accelerating collagen deposition, upregulating the expression of VEGF and key angiogenesis-related factors. In addition, composite hydrogels demonstrated excellent cytocompatibility and hemocompatibility, which holds great promise for clinical application in DW treatment. Full article
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51 pages, 38711 KB  
Article
Design and Synthesis of Novel Morpholine-Derived Nitrogen-Rich Scaffolds as Multifunctional Anticancer and Antibacterial Agents: Biological Evaluation and Computational Studies
by Hagar S. El-Hema, Esraa Adel, Wagdy I. El-Dougdoug, Ashraf A. F. Wasfy, Ahmed F. El-Sayed, Eman S. Nossier, Modather F. Hussein, Reem Binsuwaidan, Asmaa Saleh and Adel A. -H. Abdel-Rahmanh
Pharmaceutics 2026, 18(8), 982; https://doi.org/10.3390/pharmaceutics18080982 - 9 Aug 2026
Viewed by 440
Abstract
Background/Objectives: The development of multifunctional small molecules capable of simultaneously addressing cancer progression and antimicrobial resistance represents an important challenge in medicinal chemistry. This study aimed to design, synthesize, and biologically evaluate a series of novel morpholine-based nitrogen-rich heterocyclic hybrids as potential anticancer [...] Read more.
Background/Objectives: The development of multifunctional small molecules capable of simultaneously addressing cancer progression and antimicrobial resistance represents an important challenge in medicinal chemistry. This study aimed to design, synthesize, and biologically evaluate a series of novel morpholine-based nitrogen-rich heterocyclic hybrids as potential anticancer and antibacterial agents, supported by computational investigations. Methods: Twelve morpholine-derived nitrogen-enriched heterocyclic hybrids incorporating pyran, triazine, pyrimidinone, and sulfur-containing scaffolds were synthesized and fully characterized using IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. Their antiproliferative activities were evaluated against MCF-7 and HCT-116 cancer cell lines. The most active compounds were further investigated through kinase inhibition assays, cell cycle analysis, apoptosis, mitochondrial membrane potential, intracellular ROS determination, and apoptosis-related gene expression. Antibacterial, antibiofilm, antioxidant, and computational studies, including molecular docking, molecular dynamics simulations, MM-GBSA/MM-PBSA binding free-energy calculations, DFT calculations, and ADMET prediction, were also performed. Results: Compounds 3, 10, and 12 exhibited the highest antiproliferative activity, with compound 10 emerging as the lead candidate. It potently inhibited EGFR, PI3K, and mTOR, with IC50 values of 0.086 ± 0.003, 0.107 ± 0.005, and 0.223 ± 0.008 μM, respectively. Mechanistic investigations revealed G2/M arrest in MCF-7 cells and G0/G1 arrest in HCT-116 cells, accompanied by apoptosis rates of 32.66% and 37.12%; mitochondrial membrane depolarization; a 3.55-fold increase in intracellular ROS; upregulation of caspase-3, caspase-9, and Bax; and downregulation of Bcl-2, supporting activation of the intrinsic apoptotic pathway. Compound 10 also displayed the broadest antibacterial spectrum, surpassed ciprofloxacin against several tested isolates, exhibited MIC values of 5–20 μg/mL, achieved 42.80% inhibition of Pseudomonas aeruginosa biofilm formation, and showed the strongest antioxidant activity in DPPH and ABTS assays. Computational analyses supported the experimental findings by predicting stable interactions with EGFR and Staphylococcus aureus DNA gyrase, together with favorable MM-GBSA/MM-PBSA binding free energies of −23.44 and −24.99 ± 2.71 kcal/mol, respectively. Conclusions: The present findings identify compound 10 as a promising multifunctional lead with potent anticancer, antibacterial, antibiofilm, antioxidant, and multitarget kinase inhibitory activities. The combined biochemical, cellular, and computational findings support the proposed involvement of the EGFR/PI3K/mTOR signaling pathway in its antiproliferative activity and identify DNA gyrase as a potential antibacterial target. Nevertheless, the present study is limited to in vitro biological evaluation and computational investigations. Therefore, further in vivo efficacy studies, pharmacokinetic profiling, toxicity assessment, and experimental validation of the proposed molecular targets are warranted before considering preclinical development. Full article
(This article belongs to the Section Drug Targeting and Design)
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17 pages, 1714 KB  
Article
Generation and Application of Ultra-Fine, Long-Term Stable Nanobubble Water: An Evaluation of Inclusion Effects on Aromatic Components and Antimicrobial Activity
by Shin Shimizu, Mikiko Tanaka, Nanami Tominaga, Katsuyuki Fujinami, Keita Takanashi and Katsuaki Dan
Int. J. Mol. Sci. 2026, 27(15), 6909; https://doi.org/10.3390/ijms27156909 - 1 Aug 2026
Viewed by 378
Abstract
Nano- and pico-bubble water (NPB), containing hydrogen or ozone, is widely used as a cleaning agent due to its bactericidal and antiviral properties. However, some products—such as certain hydrogen waters—contain only large bubbles or have an extremely low bubble count, making them sometimes [...] Read more.
Nano- and pico-bubble water (NPB), containing hydrogen or ozone, is widely used as a cleaning agent due to its bactericidal and antiviral properties. However, some products—such as certain hydrogen waters—contain only large bubbles or have an extremely low bubble count, making them sometimes indistinguishable from ordinary drinking water. To accurately evaluate NPB activity, we developed a method for producing ultra-nano–pico-bubble water (NanoGAS water [NGW]), an ultra-fine bubble water that is stable and non-volatile over extended periods. By combining a mixed gas–liquid fluid rotary mixer and a shear filter, we produced ultra-fine bubbles that could be sealed in water. This method produced bubbles that remained stable in water even after 10 years since production. NGW has been clinically evaluated as a solvent for fecal microbiota transplantation (FMT) and has been demonstrated to be effective at improving bacterial engraftment in the intestinal tract in patients with autism spectrum disorder (ASD). Furthermore, encapsulating specific gases (hydrogen and ozone) can achieve more diverse effects. In this study, we evaluated the aroma-encapsulating effects, as well as the strength and persistence of the antimicrobial activity, of novel NGW formulations (Air-NGW, H2-NGW, S-O3-NGW, and L-O3-NGW). Both H2-NGW and O3-NGW generated in this study demonstrated slight inclusion activity with volatile aromatic compounds (citral). Furthermore, both H2-NGW (at ≥10% dilution) and O3-NGW (even at a 1% dilution) exhibited sustained antibacterial efficacy against general viable bacteria for 24 weeks. Moreover, additive effects were observed when combined with antibacterial and antiviral compounds (polyoxometalates) developed by the authors. While further consideration, including cost-effectiveness, is needed to translate these findings into practical applications, they provide a fundamental framework for future research. Full article
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24 pages, 5540 KB  
Article
Comprehensive Characterization of a Novel Broad-Host-Range Lytic Salmonella Phage WP110 and Its Biocontrol Potential Across the Broiler Value Chain
by Wattana Pelyuntha, Wichanan Wannasrichan, Haemarat Khongkhai, David Yembilla Yamik, Mingkwan Yingkajorn, Vincent Guyonnet and Kitiya Vongkamjan
Antibiotics 2026, 15(8), 747; https://doi.org/10.3390/antibiotics15080747 - 31 Jul 2026
Viewed by 386
Abstract
Background/Objectives: Salmonella enterica (S. enterica) is a major poultry-associated foodborne pathogen and a persistent public health concern. The global rise in antimicrobial resistance has accelerated the search for alternative control strategies, including the use of bacteriophages. However, their successful application requires [...] Read more.
Background/Objectives: Salmonella enterica (S. enterica) is a major poultry-associated foodborne pathogen and a persistent public health concern. The global rise in antimicrobial resistance has accelerated the search for alternative control strategies, including the use of bacteriophages. However, their successful application requires a comprehensive evaluation of their biological performance, genomic safety, and functional proteins. This study aimed to characterize Salmonella phage WP110 and assess its potential as a biocontrol agent in broiler-associated production systems. Methods: Phage WP110 was evaluated against 251 S. enterica isolates from broiler-related sources. Adsorption kinetics, one-step growth, environmental stability (temperature and pH), and effective multiplicity of infection (MOI) were determined using Salmonella Kentucky S1H28. Whole-genome sequencing (WGS) and bioinformatic analyses were performed for genome annotation, taxonomic classification, and safety evaluation. In addition, protein structural prediction of a putative endolysin (WP110-gp057) was conducted using AlphaFold2, followed by structural comparison and molecular docking with peptidoglycan. Biocontrol efficacy was evaluated in contaminated rice husk, chicken meat, and on non-food materials. Results: Phage WP110 demonstrated a broad lytic spectrum, lysing 248/251 S. enterica isolates (98.8%). It adsorbed rapidly (within 3–15 min) to host cells and exhibited a latent period of ~20 min with a burst size of 134 particles per infected cell. Phage WP110 remained stable at 4–45 °C and pH 5–11 but was inactivated at ≥75 °C and pH 2. Complete bacterial inactivation in broth assay was achieved at an MOI of 104. Genomic analysis revealed a 110,216 bp linear dsDNA genome (39.74% GC) comprising 204 ORFs, 25 tRNAs, and long direct terminal repeats, with no detectable antibiotic resistance genes. Phylogenetic and intergenomic analyses classified phage WP110 as a novel species within the genus Epseptimavirus. Structural modeling of WP110-gp057 revealed conserved catalytic residues and high structural similarity to T5 endolysin, while docking analysis supported a structurally plausible interaction with peptidoglycan at the predicted active-site groove, consistent with its proposed role in host cell wall degradation. In application models, phage WP110 significantly reduced Salmonella contamination in rice husk (up to 4.3 log CFU/g), chicken meat (up to 1.7 log CFU/g), and on non-food material surfaces (0.7–1.5 log CFU reduction). Conclusions: Phage WP110 is a broad-host-range lytic phage with favorable infection kinetics, environmental robustness, and genomic safety. Its functionally supported endolysin and strong antibacterial efficacy across broiler-associated matrices highlight its potential as a biocontrol agent for Salmonella mitigation in poultry value chain. Full article
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28 pages, 6172 KB  
Review
Bioactive Compounds from Mangrove-Associated Fungi as Leads Against ESKAPE Pathogens
by Shivankar Agrawal, Laurent Dufossé, Sunil Kumar Deshmukh and Shilpa A. Verekar
Life 2026, 16(8), 1272; https://doi.org/10.3390/life16081272 - 31 Jul 2026
Viewed by 266
Abstract
The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public [...] Read more.
The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public health challenges, contributing to increased morbidity, mortality, and healthcare costs. The limited development of new antibiotic classes over the past two decades has intensified the search for structurally novel antimicrobial agents and adjuvants capable of overcoming multidrug resistance. Natural products continue to serve as an invaluable source of anti-infective drug leads owing to their remarkable structural diversity and broad spectrum of biological activities. Mangrove ecosystems, located at the interface of terrestrial and marine environments, harbor highly diverse microbial communities, including fungi that have evolved under extreme environmental conditions and produce a wide range of unique secondary metabolites. Beyond their ecological significance, mangrove-associated fungi have emerged as prolific producers of bioactive compounds with promising antibacterial activity against multidrug-resistant pathogens. This review comprehensively summarizes recent advances (2018–2026) in the discovery of antibacterial metabolites from mangrove-associated fungi active against ESKAPE pathogens, which discusses their structural diversity, reported antimicrobial activities, and emerging strategies for accelerating natural product discovery, including genome mining, metabolomics, OSMAC, adaptive laboratory evolution, and artificial intelligence-assisted approaches. A total of 139 chemically distinct metabolites (Compounds 1139) isolated from mangrove-associated fungi are critically reviewed, highlighting their potential as promising leads for the development of next-generation antimicrobial agents against ESKAPE pathogens. Full article
(This article belongs to the Special Issue Bioactive Natural Products: From Exploration to Therapeutic Potential)
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23 pages, 5142 KB  
Article
Synthesis and Biological Evaluation of Novel C-28 Chloroacetamide-Modified Ursolic Acid Derivatives as Antibacterial Agents
by Nan Cai, Tian Luan, Junchao Zhang, Ning Li, Xiu Zhang, Peng Gao, Jiaxuan Li, Hongyu Zhan, Fanhao Meng and Dajun Zhang
Microorganisms 2026, 14(8), 1685; https://doi.org/10.3390/microorganisms14081685 - 31 Jul 2026
Viewed by 327
Abstract
The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel [...] Read more.
The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel UA derivatives (A1A7 and B1B19) were designed and synthesized by introducing various substituents at the C-28 carboxyl group via a chloroacetyl chloride linker. Their antibacterial activities were evaluated against S. aureus, S. epidermidis, E. coli, and P. aeruginosa using the microbroth dilution method. Among them, compound B1 exhibited the most potent activity, with a minimum inhibitory concentration (MIC) of 37.5 μg/mL against S. aureus and 75 μg/mL against E. coli. Antibacterial kinetic and time-kill curve assays confirmed the sustained bactericidal effect of B1. Furthermore, B1 significantly inhibited biofilm formation in both S. aureus and E. coli in a time-dependent manner. Molecular docking studies revealed that B1 binds spontaneously to the S. aureus SarA protein through three hydrogen bonds and π-π stacking interactions, providing a structural basis for its antibacterial and anti-biofilm activities. This study demonstrates that piperazine-modified UA derivative B1 is a promising antibacterial candidate and offers a new strategy for the structural optimization of ursolic acid. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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13 pages, 1634 KB  
Article
A Novel Ag/AgCl/Ag3PO4 Nanocomposite Demonstrates Potent Antibacterial Activity Against Multidrug-Resistant and Pan-Resistant Pathogenic Isolates of Acinetobacter baumannii
by Victor Hugo Montini, Laura Santana Buso, Anastácia Nikolaos Deonas, Gabriel Henrique Maximino Santos, Bruna Carolina Gonçalves, Maria Luiza Francisconi Lubanco Thomé, Paulo Rogério Catarini da Silva, Diego Prudencio dos Santos, Cesar Ricardo Teixeira Tarley, Admilton Gonçalves de Oliveira, Danielle Lazarin Bidóia, Renata Katsuko Takayama Kobayashi and Gerson Nakazato
Microorganisms 2026, 14(8), 1682; https://doi.org/10.3390/microorganisms14081682 - 31 Jul 2026
Viewed by 336
Abstract
Acinetobacter baumannii is a microorganism of major global clinical importance, whose carbapenem-resistant phenotype is considered a priority target for the development of new antimicrobial agents. Carbapenem-resistant A. baumannii is associated with healthcare-associated infections and exhibits high mortality rates, prolonged hospital stays, and extensive [...] Read more.
Acinetobacter baumannii is a microorganism of major global clinical importance, whose carbapenem-resistant phenotype is considered a priority target for the development of new antimicrobial agents. Carbapenem-resistant A. baumannii is associated with healthcare-associated infections and exhibits high mortality rates, prolonged hospital stays, and extensive use of intensive care units. As a control strategy, green-synthesized silver nanoparticles have gained increasing attention. Based on this, the aim of this study was to synthesize a novel triphasic silver nanocomposite, characterize it, and evaluate its antibacterial activity against extensively drug-resistant and pan-drug-resistant isolates. The nanocomposite was synthesized using cell-free bacterial supernatant and was physicochemically characterized regarding concentration, size, morphology, and crystallinity. Its antibacterial activity was assessed using broth microdilution and time–kill assays, followed by toxicity assays using human erythrocytes. A nanoscale and stable nanocomposite was obtained and was composed of metallic silver, silver chloride, and silver phosphate, which exhibited antibacterial activity against all tested isolates. In the toxicity assay, the nanocomposite demonstrated low toxicity and a high selectivity index. These findings demonstrate that Ag/AgCl/Ag3PO4 nanocomposite exhibits strong activity against resistant phenotypes for which therapeutic options are limited, highlighting its potential as a control strategy against this pathogen. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Alternatives)
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26 pages, 4533 KB  
Article
Mineral–Botanical Hybrid Nanofibrous Dressing for Post-Surgical Melanoma Wound Healing
by Tubanur Avci, Eray Altan, Ceren Aytar, Zehra Kanli, Elif Kaya, Serap Ayaz Seyhan, Savas Evran, Gulgun Bosgelmez Tinaz, Oguzhan Gunduz, Canan Dogan and Ahmet Akif Kızılkurtlu
Polymers 2026, 18(15), 1857; https://doi.org/10.3390/polym18151857 - 29 Jul 2026
Viewed by 641
Abstract
Melanoma excision procedures frequently result in complex wounds that require simultaneous tumor suppression and tissue regeneration. However, current post-surgical care heavily relies on synthetic drugs, facing challenges like antibiotic resistance and delayed healing. To address this notable gap, this study introduces a novel [...] Read more.
Melanoma excision procedures frequently result in complex wounds that require simultaneous tumor suppression and tissue regeneration. However, current post-surgical care heavily relies on synthetic drugs, facing challenges like antibiotic resistance and delayed healing. To address this notable gap, this study introduces a novel “mineral-botanical” hybrid nanofibrous dressing to reduce reliance on conventional synthetic agents. The nanofiber surfaces were subsequently functionalized with a supercritical CO2 extract of Inula helenium, thereby introducing a highly bioactive botanical agent not previously explored in this hybrid wound-care context. Comprehensive physical and structural characterizations demonstrated that the bioactive coating serves as a resilient physical barrier, significantly enhancing the dressing’s structural integrity in fluidic environments. In vitro biological evaluations revealed a dual-action mechanism: the biomaterial exhibited excellent biocompatibility and accelerated migration in human dermal fibroblasts (HDFs), achieving nearly 100% in vitro wound closure at 24 h. Conversely, the Inula helenium-coated nanofibers demonstrated distinct, selective cytotoxicity against A375 melanoma cells, effectively restricting their proliferation and reducing their viability. Furthermore, the hybrid platform exhibited significant antioxidant potential and achieved 94% antibacterial inhibition against Staphylococcus aureus. In conclusion, this study presents a sustainable, dual-function wound dressing that suppresses residual cancer cells while promoting healthy tissue regeneration, offering a promising alternative to conventional synthetic oncological dressings. Full article
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9 pages, 226 KB  
Article
High In Vitro Activity of the Novel Pleuromutilin Antibiotic, Lefamulin, on Clinical Helicobacter pylori Isolates
by Lyudmila Boyanova, Liliya Yordanova Boyanova, Victor Kamburov, Nayden Kandilarov, Nikolay Katsarov, Raina Gergova, Vasil Svetoslavov Boyanov and Rumyana Markovska
Antibiotics 2026, 15(8), 734; https://doi.org/10.3390/antibiotics15080734 - 29 Jul 2026
Viewed by 320
Abstract
Background: Antibiotic resistance in Helicobacter pylori is steadily increasing, rendering the treatment of related gastroduodenal diseases increasingly difficult. Lefamulin is a new broad-spectrum antibacterial in the pleuromutilin class, acting by suppressing bacterial protein synthesis. It has the advantages of its unique “induced-fit” [...] Read more.
Background: Antibiotic resistance in Helicobacter pylori is steadily increasing, rendering the treatment of related gastroduodenal diseases increasingly difficult. Lefamulin is a new broad-spectrum antibacterial in the pleuromutilin class, acting by suppressing bacterial protein synthesis. It has the advantages of its unique “induced-fit” mechanism, a low frequency of spontaneous mutations, stepwise development of resistance, stability in acidic environments, and potential for additive or synergistic activity when combined with certain other antibiotics against various facultative anaerobes, including multidrug-resistant isolates. Methods: We investigated, for the first time to the best of our knowledge, the activity of lefamulin against 91 clinical H. pylori isolates from symptomatic adult patients using MIC test strips. Results: Overall, lefamulin MICs50 and MICs90 were 0.25 and 2 mg/L versus 4 and ≥256 mg/L for clarithromycin, and 0.75 and ≥32 mg/L, respectively, for levofloxacin. Lefamulin MICs50 and MICs90 were 0.5 mg/L and 4 mg/L against the 61 clarithromycin-resistant (MICs, >0.25 mg/L) isolates, 0.25 and 0.75 mg/L against the 40 levofloxacin-resistant (MICs, >1 mg/L) isolates, and 0.38 mg/L and 0.75 mg/L, respectively, against the 28 isolates resistant to both agents. Conclusions: Briefly, the new pleuromutilin antibiotic outperformed in vitro both clarithromycin and levofloxacin against H. pylori isolates. Its potential usefulness in treating H. pylori infections resistant to macrolides and fluoroquinolones, and especially those with dual resistance, justifies further investigation. However, some precautions should also be considered. The use of the novel antibiotic lefamulin may offer benefits for H. pylori eradication if our results are confirmed in subsequent studies, including clinical trials. Full article
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