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16 pages, 3808 KB  
Article
Flexible Copper-Based TEM Grid for Microscopic Characterization of Aged Magnetotactic Bacteria MS-1 and Their Magnetosome Crystals in Air-Dried Droplet
by Natalia Lorela Paul, Regis Deturche, Jeremie Beal, Catalin Ovidiu Popa and Rodica Elena Ionescu
Molecules 2026, 31(2), 253; https://doi.org/10.3390/molecules31020253 - 12 Jan 2026
Viewed by 185
Abstract
Magnetotactic bacteria (MTB) have attracted interest in recent years, mainly due to their natural ability to form intracellular magnetic nanocrystals with potential for biomedical and environmental applications. In this study, we focused on the morphological analysis of the Paramagnetospirillum magnetotacticum MS-1 strain, trying [...] Read more.
Magnetotactic bacteria (MTB) have attracted interest in recent years, mainly due to their natural ability to form intracellular magnetic nanocrystals with potential for biomedical and environmental applications. In this study, we focused on the morphological analysis of the Paramagnetospirillum magnetotacticum MS-1 strain, trying to keep the bacteria as close to their natural state as possible. An important element of this work is the use of untreated bacterial cells, without conductive coating or chemical fixation, using a simple and low-cost support. This choice was made intentionally to avoid changes induced by metallization and to allow direct observation of characteristics that may be relevant in applications where the interaction of the bacteria with the environment plays an important role, such as biosensors. In addition, the analysis was performed on a bacterial suspension stored for approximately 10 months at 4 °C to assess whether the morphology specific to the MS-1 strain is maintained over time. The obtained results show that the general cell morphology and magnetosome organization can be clearly and reproducibly observed even after long-term storage. Without attempting to replace studies based on conventional sample preparation methods, this work provides a complementary perspective and suggests that magnetotactic bacteria may represent a natural and effective alternative to synthetic magnetic nanoparticles, with potential applications in the biomedical and environmental fields. Full article
(This article belongs to the Special Issue Functional Nanomaterials for Biosensors and Biomedicine Application)
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25 pages, 1658 KB  
Review
Biogenic Approaches to Metal Nanoparticle Synthesis and Their Application in Biotechnology
by Yulia Yugay and Yury Shkryl
Plants 2026, 15(2), 183; https://doi.org/10.3390/plants15020183 - 7 Jan 2026
Viewed by 457
Abstract
Metal and metal oxide nanoparticles (NPs) synthesized through biologically mediated reduction of metal ions using biomolecules derived from microorganisms, algae, or plants are attracting growing attention in plant biotechnology due to their multifunctional properties and environmental advantages compared with conventional physicochemical synthesis. This [...] Read more.
Metal and metal oxide nanoparticles (NPs) synthesized through biologically mediated reduction of metal ions using biomolecules derived from microorganisms, algae, or plants are attracting growing attention in plant biotechnology due to their multifunctional properties and environmental advantages compared with conventional physicochemical synthesis. This review provides a comprehensive analysis of biological approaches for NP production using bacteria, fungi, algae, cyanobacteria, whole plants, and in vitro plant cell cultures. The main biosynthetic mechanisms, types of reducing and capping metabolites, metal specificity, and typical NP characteristics are described for each system, with emphasis on their relative productivity, scalability, reproducibility, and biosafety. Special consideration is given to plant cell and tissue cultures as highly promising platforms that combine the metabolite diversity of whole plants with precise control over growth conditions and NP parameters. Recent advances highlight the significance of bioengineering of reductive capacity as a novel strategy to enhance the efficiency and controllability of NP biosynthesis. Since NP formation is driven by key biomolecules, targeted modification of biosynthetic pathways through metabolic and genetic engineering can substantially increase NP yield and allow fine-tuning of their structural and functional properties. The applications of biogenic NPs in plant biotechnology are systematically evaluated, including their use as environmentally safe disinfectants for explants and seed sterilization, modulators of callus induction and morphogenesis, and abiotic elicitors that enhance the accumulation of economically valuable secondary metabolites. Remaining challenges, such as variability in NP characteristics, limited scalability, and insufficient data on phytotoxicity and environmental safety, are discussed to outline future research priorities. The synthesis–function relationships highlighted here provide a foundation for developing sustainable NP-based technologies in modern agriculture. Full article
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23 pages, 5498 KB  
Article
The Effect of a Cactus-Based Natural Coagulant on the Physical–Chemical and Bacteriological Quality of Drinking Water: Batch and Continuous Mode Studies
by Abderrezzaq Benalia, Ouiem Baatache, Kerroum Derbal, Amel Khalfaoui, Loqmen Atime, Antonio Pizzi, Gennaro Trancone and Antonio Panico
Water 2026, 18(2), 138; https://doi.org/10.3390/w18020138 - 6 Jan 2026
Viewed by 394
Abstract
Cactus leaves from the Cactaceae family, particularly the Opuntia genus, have attracted increasing attention as natural coagulants for water treatment applications. In this work, Cactus-based extracts were investigated for drinking water treatment through the coagulation–flocculation process. Several extraction routes were examined, including [...] Read more.
Cactus leaves from the Cactaceae family, particularly the Opuntia genus, have attracted increasing attention as natural coagulants for water treatment applications. In this work, Cactus-based extracts were investigated for drinking water treatment through the coagulation–flocculation process. Several extraction routes were examined, including Ca-J, Ca-H2O, Ca-NaOH (0.05 M), Ca-NaCl (0.5 M), and Ca-HCl (0.05 M), and their performance was evaluated using jar test experiments. The removal efficiencies of total coliforms (TC), anaerobic sulfite-reducing bacteria (ASRB), total suspended solids (TSS), and turbidity were assessed, and the most effective extract was subsequently tested in a semi-industrial pilot-scale coagulation–flocculation–settling system. The physicochemical properties of the Cactus material were characterized using FTIR, SEM, XRD, and MALDI-TOF analyses. Results revealed bioactive components, including carbohydrates, proteins, tannins, flavonoids, and glucose, with functional groups (carboxyl, hydroxyl, carbonyl) responsible for coagulation. XRD and SEM analyses showed a semi-crystalline structure and a heterogeneous surface with fiber networks, while MALDI-TOF confirmed the presence of flavonoid and tannin compounds. These features collectively contribute to the effective removal of turbidity, suspended solids, and microbial contaminants. Among the tested extracts, Ca-NaOH (0.05 M) exhibited the highest removal efficiencies, achieving 100% removal of TC and ASRB, 94.15% removal of TSS, and 70.38% turbidity reduction under laboratory conditions. Pilot-scale application of this extract resulted in a turbidity reduction of 66.65%. Additional water quality parameters, including total alkalinity (TA), total dissolved solids (TDS), pH, and electrical conductivity (EC), were monitored to evaluate process performance. Overall, the results highlight the strong potential of Cactus leaves as an effective, cost-efficient, and environmentally friendly alternative to conventional chemical coagulants. However, further research is required to enhance their scalability and commercialization. Full article
(This article belongs to the Section Water Quality and Contamination)
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17 pages, 2371 KB  
Article
Cyclic Amide-Linked Oxazolidinone Triazoles as Inhibitors of the T-Box Riboswitch
by Eric Parsons, Ali H. Aldhumani, Emily A. Fairchild, Oluwaseun B. Adegbite, Jessica M. Roberts, Jennifer V. Hines and Stephen C. Bergmeier
Molecules 2026, 31(1), 29; https://doi.org/10.3390/molecules31010029 - 22 Dec 2025
Viewed by 294
Abstract
Antimicrobial resistance remains a critical global health challenge, and was intensified by the COVID-19 pandemic. To address this growing threat, novel antibacterial agents targeting unconventional mechanisms are urgently needed. One promising strategy involves inhibiting bacterial riboswitches—RNA elements that regulate gene expression. Unlike most [...] Read more.
Antimicrobial resistance remains a critical global health challenge, and was intensified by the COVID-19 pandemic. To address this growing threat, novel antibacterial agents targeting unconventional mechanisms are urgently needed. One promising strategy involves inhibiting bacterial riboswitches—RNA elements that regulate gene expression. Unlike most riboswitches that respond to small-molecule metabolites, the T-box riboswitch uniquely binds non-aminoacylated tRNA and is predominantly found in Gram-positive bacteria, making it an attractive target due to its conserved sequences and regulatory role over essential genes. This study explored oxazolidinone- and triazole-based compounds as potential inhibitors of the T-box riboswitch. Prior investigations into tricyclic oxazolidinones revealed an allosteric modulator that effectively inhibited T-box riboswitch transcriptional readthrough in vitro, though it showed limited disruption of the isolated tRNA–antiterminator complex. To enhance RNA-binding affinity and stereoselectivity, a macrocyclic oxazolidinone scaffold was designed, incorporating a strategic substituent to expand the interaction footprint. A synthetically viable candidate was identified, and computational docking studies suggested that one of the designed compounds may interfere with tRNA-induced transcription by forming π–π stacking interactions with G5 in the antiterminator region. These findings support the potential of targeting the T-box riboswitch with structurally optimized small molecules as a novel antibacterial strategy. Full article
(This article belongs to the Section Medicinal Chemistry)
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17 pages, 1031 KB  
Article
Fractionation and Chemical Characterization of Cell-Bound Biosurfactants Produced by a Novel Limosilactobacillus fermentum Strain via Cheese Whey Valorization
by Dimitra Alimpoumpa, Harris Papapostolou, Maria Alexandri, Vasiliki Kachrimanidou and Nikolaos Kopsahelis
Foods 2025, 14(24), 4342; https://doi.org/10.3390/foods14244342 - 17 Dec 2025
Viewed by 372
Abstract
Lactic acid bacteria (LAB) have attracted scientific attention as potential producers of biosurfactants (BS); however, there is limited knowledge on the structure of the produced molecules. The aim of this study was to elucidate the individual components comprising the crude BS produced by [...] Read more.
Lactic acid bacteria (LAB) have attracted scientific attention as potential producers of biosurfactants (BS); however, there is limited knowledge on the structure of the produced molecules. The aim of this study was to elucidate the individual components comprising the crude BS produced by Limosilactobacillus fermentum ACA-DC 0183. Initially, batch fermentations using substrate recycling were employed, leading to the production of 0.76 g/L of crude BS from cheese whey as the sole carbon and nutrient source. The produced BS maintained their properties under various temperatures, pH values, and salinity levels, signifying their potential uses in food applications. Additionally, the structural components were analyzed after hydrolysis. The lipoic part was mainly composed of palmitic acid, oleic acid, and stearic acid, while 17 amino acids were identified as part of the protein moiety of the molecule. Acid hydrolysis of the carbohydrate moiety revealed that this part consisted of glucose, galactose, and glycerol. Partial purification with column chromatography and characterization using FTIR demonstrated the presence of a glycoprotein and a glycolipid as surface-active molecules. Revealing the structure and specific properties of microbially produced BS can expand their utilization in target applications, while their production from renewable sources contributes towards the sustainable production of LAB-based BS. Full article
(This article belongs to the Special Issue Sustainable Uses and Applications of By-Products of the Food Industry)
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13 pages, 1788 KB  
Article
Harnessing Algal–Bacterial Nexus for Sustainable and Eco-Friendly Wastewater Treatment
by Samar A. El-Mekkawi, Sayeda M. Abdo and Marwa Youssef
Processes 2025, 13(12), 4042; https://doi.org/10.3390/pr13124042 - 14 Dec 2025
Viewed by 344
Abstract
The accelerating pace of global population growth, urbanization, and industrialization is exerting considerable pressure on freshwater resources. In developing countries, where infrastructure constraints often hinder the adoption of advanced treatment technologies, cost-effective and efficient wastewater solutions are essential. Algal–bacterial bioremediation represents a promising, [...] Read more.
The accelerating pace of global population growth, urbanization, and industrialization is exerting considerable pressure on freshwater resources. In developing countries, where infrastructure constraints often hinder the adoption of advanced treatment technologies, cost-effective and efficient wastewater solutions are essential. Algal–bacterial bioremediation represents a promising, eco-friendly method for removing organic pollutants through biological processes. This study evaluates a hybrid treatment system composed of three ponds: a covered anaerobic pond for organic matter digestion, a microalgal pond equipped with rotating biological contactors (RBCs) that facilitate interactions between heterotrophic bacteria and diatoms, and a final settling pond. Granular activated carbon embedded within the RBC enhances biofilm formation by attracting heterotrophic bacteria, thereby increasing treatment efficiency. Under optimal conditions—10 g of activated carbon and 1.7 d hydraulic retention time—the system achieved removal efficiencies of 95.8% for total suspended solids (TSS), 96.3% for turbidity, 85% for biological oxygen demand (BOD), and 99.9% for Escherichia coli. Bacteriological analysis showed complete removal of fecal coliform and total coliform. The characteristics of the outflow treated wastewater are 3 mg/L, 0.9 NTU, and 3.2 mg/L for TSS, turbidity, and BOD, respectively, while E. coli detection is under detection limit. The treated effluent complies with Category A for the reuse of treated wastewater in the Egyptian code for the reuse of treated municipal wastewater for agricultural purposes, offering a scalable and sustainable solution for wastewater management in resource-constrained regions. Full article
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26 pages, 1660 KB  
Review
Berberine in Bowel Health: Anti-Inflammatory and Gut Microbiota Modulatory Effects
by Anna Duda-Madej, Szymon Viscardi, Jakub Piotr Łabaz, Ewa Topola, Wiktoria Szewczyk and Przemysław Gagat
Int. J. Mol. Sci. 2025, 26(24), 12021; https://doi.org/10.3390/ijms262412021 - 13 Dec 2025
Viewed by 1986
Abstract
Disruption of the gut-microbiome-brain axis contributes to the development of chronic inflammation, impaired intestinal barrier integrity, and progressive tissue damage, ultimately reducing quality of life and increasing risk of comorbidities, including neurodegenerative diseases. Current therapies are often limited by adverse effects and insufficient [...] Read more.
Disruption of the gut-microbiome-brain axis contributes to the development of chronic inflammation, impaired intestinal barrier integrity, and progressive tissue damage, ultimately reducing quality of life and increasing risk of comorbidities, including neurodegenerative diseases. Current therapies are often limited by adverse effects and insufficient long-term efficacy, highlighting the need for more comprehensive therapeutic approaches. Berberine (BRB), a plant-derived isoquinoline alkaloid, has attracted growing attention due to its pleiotropic immunomodulatory, neuroprotective, and gut-homeostasis-modulating properties, which involve reshaping the gut microbiota and underscore its therapeutic relevance within the gut–microbiome–brain axis. The aim of this review is to synthesize current scientific evidence regarding the anti-inflammatory mechanisms of BRB in inflammatory bowel disease (IBD). We compare its activity with first-line therapies and discuss its impact on microbial composition, including the bidirectional regulation of specific bacterial taxa relevant to intestinal and systemic disorders that originate in the gut. Furthermore, we emphasize that gut bacteria convert BRB into bioactive metabolites, contributing to its enhanced intraluminal activity despite its low systemic bioavailability. By integrating molecular and microbiological evidence, this review fills a critical knowledge gap regarding the comprehensive therapeutic potential of BRB as a promising candidate for future IBD interventions. The novelty of this work lies in unifying fragmented findings into a framework that explains how BRB acts simultaneously at the levels of host immunity, microbial ecology, and neuroimmune communication—thus offering a new conceptual model for its role within the gut–microbiome–brain axis. Full article
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20 pages, 1296 KB  
Article
Use of Ultrafiltration Membranes as Tertiary/Quaternary Treatment for Wastewater Reclamation in Municipal WWTPs
by Á. Sabina Acebrón, Julio Revert-Vercher, Pau Sanchis-Perucho, Luis Borrás and Aurora Seco
Water 2025, 17(24), 3453; https://doi.org/10.3390/w17243453 - 5 Dec 2025
Viewed by 642
Abstract
This work assesses the viability of ultrafiltration (UF) membranes as a substitution for classic tertiary technologies for municipal wastewater (MWW) treatment. UF membranes can offer efficient MWW filtration, meeting quality standards regarding solids, bacteria, viruses and emerging pollutants, such as microplastics. All of [...] Read more.
This work assesses the viability of ultrafiltration (UF) membranes as a substitution for classic tertiary technologies for municipal wastewater (MWW) treatment. UF membranes can offer efficient MWW filtration, meeting quality standards regarding solids, bacteria, viruses and emerging pollutants, such as microplastics. All of these make UF not only an attractive competitor regarding tertiary treatments but also a potential quaternary treatment according to the latest legislation. Indeed, the achieved permeate quality meets the more stringent parameters for water reuse in agriculture according to the European standard (A-type water). The UF membrane’s feasibility when used as an MWW tertiary/quaternary treatment was assessed in a semi-industrial plant with commercially available industrial membrane modules under different operating conditions: (1) transmembrane flux, (2) air sparging intensity and filtration/relaxation periodicities, (3) the concentration of solids reached in the membrane tank and (4) the efficacy of chemically enhanced backwashing (CEB) to mitigate fouling. Increasing the air intensity (around 0.25 m3 m−2 h−1), increasing the solids concentration (3–4 g L−1) and using acid chemicals for backwashing at low concentrations but high periodicities (about 25–50 ppm of HCl/citric acid at a pH of 2.5 once or twice every 15 days) displayed great effectiveness in minimizing fouling, which was found to be mainly reversible. Thanks to the stablished conditions, semi-industrial UF membrane filtration was possible for more than 30 days when operating at relatively high transmembrane fluxes (21.5 LMH), achieving an average transmembrane pressure of around 120 mbar with an extremely low fouling growth rate of 0.024 mbar d−1. Full article
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22 pages, 4615 KB  
Article
Selection of Candidate Bacteria for Microbial Enrichment of Soil Amendments to Manage Contaminants of Emerging Concern in Agricultural Soils
by Rossana Sidari, Maria Teresa Rodinò, Giulio Scarpino, Stefano Mocali, Sara Del Duca, Elisabetta Loffredo and Antonio Gelsomino
Agriculture 2025, 15(23), 2507; https://doi.org/10.3390/agriculture15232507 - 2 Dec 2025
Viewed by 469
Abstract
Recycled bio-wastes such as compost and vermicompost, and bioenergy byproducts such as digestate and biochar are widely acknowledged for their role as soil conditioners capable of preserving soil fertility, maintaining soil health, and acting as a bio-adsorbent of organic soil pollutants (BIOSORs). Moreover, [...] Read more.
Recycled bio-wastes such as compost and vermicompost, and bioenergy byproducts such as digestate and biochar are widely acknowledged for their role as soil conditioners capable of preserving soil fertility, maintaining soil health, and acting as a bio-adsorbent of organic soil pollutants (BIOSORs). Moreover, they are attracting increasing attention for use as effective carriers of microbial consortia into arable soils. This study aims to combine selection of bacteria tolerating contaminants of emerging concern (CECs) and their use to fortify BIOSORs. Seventeen bacterial strains isolated from commercial bio-stimulant formulations were studied together with three strains previously isolated and identified as Bacillus subtilis, Bacillus licheniformis, and Serratia plymuthica. All the strains were tested in vitro for their ability to grow under increasing concentrations (0, 0.2, 0.5 and 1 mg L−1) of CECs: bisphenol A, 4-nonylphenol, penconazole, and S-metolachlor. Results highlighted a variability in the tolerance of the bacteria to the tested CECs. The B. subtilis, B. licheniformis, and S. plymuthica were the most promising strains, individually or as consortium, to tolerate individual CECs and their mix. Moreover, they exhibited metabolic activity when inoculated in the BIOSORs. Nevertheless, additional investigations such as quantitative assessment of CECs are needed to validate the methodology. This work contributes to investigate the feasibility of stable and functionally active microbially enriched bio-sorbents (Me-BIOSORs) and provides preliminary evidence supporting the potential to be used in soil–plant systems at the field scale. Full article
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18 pages, 5210 KB  
Article
Influence Pattern and Mechanism of Increased Nitrogen Deposition and AM Fungi on Soil Microbial Community in Desert Ecosystems
by Hui Wang, Wan Duan, Qianqian Dong, Zhanquan Ji, Wenli Cao, Fangwei Zhang, Wenshuo Li and Yangyang Jia
Microorganisms 2025, 13(12), 2660; https://doi.org/10.3390/microorganisms13122660 - 22 Nov 2025
Viewed by 419
Abstract
With continuous increases in nitrogen (N) deposition in the future, its impacts on terrestrial ecosystems are attracting growing concern. Arbuscular mycorrhiza (AM) fungi play a crucial role in shaping both soil microbial and plant communities. AM fungi play a crucial role in shaping [...] Read more.
With continuous increases in nitrogen (N) deposition in the future, its impacts on terrestrial ecosystems are attracting growing concern. Arbuscular mycorrhiza (AM) fungi play a crucial role in shaping both soil microbial and plant communities. AM fungi play a crucial role in shaping the soil microbial and plant communities, yet their patterns of influence under increased N deposition scenarios remain unclear, particularly in desert ecosystems. Therefore, we conducted a field experiment simulating increased N deposition and AM fungal suppression to assess the effects of increased N deposition and AM fungi on soil microbial communities, employing phospholipid fatty acid (PLFA) biomarker technology in the Gurbantunggut Desert of Xinjiang. We found that increased N deposition promoted soil microbial biomass, including AM fungi, fungi, Actinomycetes (Act), Gram-positive bacteria (G+), Gram-negative bacteria (G), and Dark Septate Endophyte (DSE). AM fungal suppression significantly increased the content of soil Act and G+. There were clearly and significantly interactive effects of increased N deposition and AM fungi on soil microbial contents. Both increased N deposition and AM fungi caused significant changes in soil microbial community structure. Random forest analysis revealed that soil nitrate N (NO3-N), Soil Organic Carbon (SOC), and pH were main factors influencing soil microorganisms; soil AM fungi, G+, and Act significantly affected plant Shannon diversity; soil G, Act, and fungi posed significant effects on plant community biomass. Finally, the structure equation model results indicated that soil fungi, especially AM fungi, were the main soil microorganisms altering the plant community diversity and biomass under increased N deposition. This study reveals the crucial role of AM fungi in regulating soil microbial responses to increased N deposition, providing experimental evidence for understanding how N deposition affects plant communities through soil microorganisms. Full article
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19 pages, 1857 KB  
Review
Use of Formaldehyde in Poultry Production for the Treatment of Litter, Hatching Eggs, Hatcheries, and Feed: An Updated Mini Review
by Pedro Henrique Gomes de Sá Santos, Gabriel da Silva Oliveira, Concepta McManus and Vinícius Machado dos Santos
Toxics 2025, 13(11), 1003; https://doi.org/10.3390/toxics13111003 - 20 Nov 2025
Viewed by 886
Abstract
Bacteria such as Salmonella spp. are primarily transmitted through contaminated eggs and infected poultry; however, other routes, including the movement of personnel, vehicles, and lapses in biosecurity protocols, also play a significant role in their dissemination within poultry systems. Control of a wide [...] Read more.
Bacteria such as Salmonella spp. are primarily transmitted through contaminated eggs and infected poultry; however, other routes, including the movement of personnel, vehicles, and lapses in biosecurity protocols, also play a significant role in their dissemination within poultry systems. Control of a wide range of microorganisms, including bacteria, is often carried out using chemical agents, such as formaldehyde, applied in its solid, liquid, or gaseous forms. Reports on the use of formaldehyde in poultry production date back more than a century. However, it continues to attract research interest due to growing concerns about bacterial resistance, embryotoxicity, occupational exposure, the generation of toxic byproducts, and the search for safer alternatives in poultry production systems. It remains widely used worldwide, but comprehensive and updated evaluations of its efficacy, toxicity, and risks to both poultry and workers are still limited. This review aims to synthesize the current knowledge on the use of formaldehyde in poultry production. Overall, the synthesis shows that formaldehyde remains an effective but high-risk sanitizer whose continued use in poultry systems requires rigorous control and monitoring protocols, and that the development and adoption of efficient and safer alternatives is recommended. Full article
(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)
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23 pages, 3339 KB  
Article
Serendipitous Hinge Modulation Hypothetically Reprograms Caerin 1.1-LC Antibacterial Mechanism and Gram-Negative Selectivity
by Zhengze Sun, Ruixin Zhao, Yueao Zhang, Xiaonan Ma, Yangyang Jiang, Tao Wang, Xiaoling Chen, Chengbang Ma, Tianbao Chen, Chris Shaw, Mei Zhou and Lei Wang
Pharmaceutics 2025, 17(11), 1500; https://doi.org/10.3390/pharmaceutics17111500 - 20 Nov 2025
Viewed by 649
Abstract
Background: The golden era of antibiotics has long passed, and the clinical failures caused by emerging drug-resistant bacteria have intensified the demand for novel antimicrobial agents. Antimicrobial peptides have attracted significant attention as promising candidates for next-generation antibiotics. Methods: In this study, we [...] Read more.
Background: The golden era of antibiotics has long passed, and the clinical failures caused by emerging drug-resistant bacteria have intensified the demand for novel antimicrobial agents. Antimicrobial peptides have attracted significant attention as promising candidates for next-generation antibiotics. Methods: In this study, we identified a novel antimicrobial peptide, Caerin 1.1-LC, from the skin secretion of the Australian green tree frog, Litoria caerulea. Subsequent structure–activity relationship studies led us to design a series of analogues and revealed the critical role of the peptide’s intrinsic hinge structure in shaping its biological activity. Results: Incorporation of D-isomers at the valine residues within the hinge preserved overall helical content but altered the hinge conformation, resulting in an 8-fold increase in antibacterial activity against Gram-negative bacteria. Simultaneously, haemolytic activity was markedly reduced, leading to a 56-fold improvement in therapeutic index (from 0.47 to 26.6). Structural modulation of the hinge also switched the mechanism of action from classical membrane disruption with associated permeability changes to a non-membrane-permeabilising, ‘cell-penetrating-like’ behaviour, inducing membrane potential depolarisation and ATP disruption to trigger bacterial death. In vivo studies using infected larval models, along with in vitro LPS neutralisation assays, further demonstrated the therapeutic potential of the D-analogue as a novel antibacterial agent. Conclusions: This work highlights the pivotal role of hinge structures in Caerin-family/hinge-containing AMPs, offering a strategic avenue for optimising antibacterial efficacy. Full article
(This article belongs to the Special Issue Antimicrobial Peptides as Promising Therapeutic Agents)
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14 pages, 1926 KB  
Article
Skin Whitening Effect and Molecular Mechanism of Phenyllactic Acid (PLA) Derived from Limosilactobacillus reuteri Culture Broth
by Ki-Min Kim, Seo-Yeon Shin, Nu-Ri Song, Jae-Hee Byun, Seon-Ju Kim, Sun Oh Kim and Kyung-Mok Park
Cosmetics 2025, 12(6), 258; https://doi.org/10.3390/cosmetics12060258 - 14 Nov 2025
Viewed by 1293
Abstract
Skin hyperpigmentation is primarily regulated by melanogenesis, in which tyrosinase and related enzymes play pivotal roles. Probiotics have recently been attracting attention as a cosmetic ingredient due to their skin-friendly and eco-friendly properties. In particular, microbial metabolites, known as postbiotics, are gaining attention [...] Read more.
Skin hyperpigmentation is primarily regulated by melanogenesis, in which tyrosinase and related enzymes play pivotal roles. Probiotics have recently been attracting attention as a cosmetic ingredient due to their skin-friendly and eco-friendly properties. In particular, microbial metabolites, known as postbiotics, are gaining attention for their superior safety, stability, and efficacy compared with probiotics. In this study, we investigated the whitening effect and molecular mechanisms of phenyllactic acid (PLA), a metabolite derived from Limosilactobacillus reuteri (L. reuteri) culture broth. In B16F10 melanoma cells, the effects of PLA were evaluated by measuring melanin content, cellular tyrosinase activity, enzyme kinetics, and the expression of melanogenesis-related proteins. PLA significantly inhibited melanin production and cellular tyrosinase activity in α-MSH–stimulated B16F10 melanoma cells without inducing cytotoxicity. PLA downregulated tyrosinase-related proteins such as TRP-1 and TRP-2, and competitively inhibited tyrosinase. The inhibition constants (Ki) for L-tyrosine and L-DOPA were 12.63 mM and 0.68 mM, respectively. These findings suggest that PLA, a postbiotic derived from lactic acid bacteria, may serve as a safe and effective whitening ingredient, providing a scientific basis for the development of functional skin-whitening cosmetics. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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43 pages, 9566 KB  
Review
Protein–Protein Interactions as Promising Molecular Targets for Novel Antimicrobials Aimed at Gram-Negative Bacteria
by Piotr Maj and Joanna Trylska
Int. J. Mol. Sci. 2025, 26(22), 10861; https://doi.org/10.3390/ijms262210861 - 9 Nov 2025
Viewed by 1675
Abstract
Antibiotic resistance, especially among Gram-negative bacterial strains, places a massive burden on global healthcare systems as resistance development has outpaced antibiotic discovery. Protein–protein interactions, successful in other therapeutic contexts, are emerging as promising, yet underexplored, targets for the development of novel classes of [...] Read more.
Antibiotic resistance, especially among Gram-negative bacterial strains, places a massive burden on global healthcare systems as resistance development has outpaced antibiotic discovery. Protein–protein interactions, successful in other therapeutic contexts, are emerging as promising, yet underexplored, targets for the development of novel classes of antibacterials. Pathogen-specific protein–protein interactions are attractive targets because they are often structurally and functionally distinct from host proteins and are less likely to elicit rapid resistance. This review summarizes recent developments in targeting protein–protein interactions in Gram-negative bacteria, focusing on the modulation of five critical cellular processes: membrane regulation, replication, transcription, translation, and toxin-antitoxin systems. We highlight the design and discovery of both small-molecule and peptide-based inhibitors. While many identified modulators exhibit potent in vitro activity against their respective targets, achieving effective penetration of the complex Gram-negative cell envelope remains a major challenge. Nevertheless, the diverse and essential nature of these bacteria-specific protein–protein interactions represents an attractive strategy for developing next-generation antimicrobials to combat drug-resistant pathogens. Full article
(This article belongs to the Section Molecular Microbiology)
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33 pages, 4181 KB  
Article
Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding
by Alexander Carreño, Vania Artigas, Belén Gómez-Arteaga, Evys Ancede-Gallardo, Marjorie Cepeda-Plaza, Jorge I. Martínez-Araya, Roxana Arce, Manuel Gacitúa, Camila Videla, Marcelo Preite, María Carolina Otero, Catalina Guerra, Rubén Polanco, Ignacio Fuentes, Pedro Marchant, Osvaldo Inostroza, Fernando Gil and Juan A. Fuentes
Int. J. Mol. Sci. 2025, 26(21), 10801; https://doi.org/10.3390/ijms262110801 - 6 Nov 2025
Viewed by 953
Abstract
Metal-free aminobenzoic acid-derived Schiff bases are attractive antimicrobial leads because their azomethine (–C=N–) functionality enables tunable electronic properties and target engagement. We investigated whether halogenation on the phenolic ring would modulate the redox behavior and enhance antibacterial potency, and hypothesized that heavier halogens [...] Read more.
Metal-free aminobenzoic acid-derived Schiff bases are attractive antimicrobial leads because their azomethine (–C=N–) functionality enables tunable electronic properties and target engagement. We investigated whether halogenation on the phenolic ring would modulate the redox behavior and enhance antibacterial potency, and hypothesized that heavier halogens would favorably tune physicochemical and electronic descriptors. We synthesized three derivatives (SB-3/Cl, SB-4/Br, and SB-5/I) and confirmed their structures using FTIR, 1H- and 13C-NMR, UV-Vis, and HRMS. For SB-5, single-crystal X-ray diffraction and Hirshfeld analysis verified the intramolecular O–H⋯N hydrogen bond and key packing contacts. Cyclic voltammetry revealed an irreversible oxidation (aminobenzoic ring) and, for the halogenated series, a reversible reduction associated with the imine; peak positions and reversibility trends are consistent with halogen electronic effects and DFT-based MEP/LHS descriptors. Antimicrobial testing showed that SB-5 was selectively potent against Gram-positive aerobes, with low-to-mid micromolar MICs across the panel. Among anaerobes, activity was more substantial: Clostridioides difficile was inhibited at 0.1 µM, and SB-3/SB-5 reduced its sporulation at sub-MICs, while Blautia coccoides was highly susceptible (MIC 0.01 µM). No activity was detected against Gram-negative bacteria at the tested concentrations. In the fungal assay, Botrytis cinerea displayed only a transient fungistatic response without complete growth inhibition. In mammalian cells (HeLa), the compounds displayed clear concentration-dependent behavior. Overall, halogenation, particularly iodination, emerges as a powerful tool to couple redox tuning with selective Gram-positive activity and a favorable cellular tolerance window, nominating SB-5 as a promising scaffold for further antimicrobial optimization. Full article
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