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Keywords = antibiotic secondary metabolites

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48 pages, 3314 KiB  
Review
Applied Microbiology for Sustainable Agricultural Development
by Barbara Sawicka, Piotr Barbaś, Viola Vambol, Dominika Skiba, Piotr Pszczółkowski, Parwiz Niazi and Bernadetta Bienia
Appl. Microbiol. 2025, 5(3), 78; https://doi.org/10.3390/applmicrobiol5030078 - 1 Aug 2025
Viewed by 86
Abstract
Background: Developments in biology, genetics, soil science, plant breeding, engineering, and agricultural microbiology are driving advances in soil microbiology and microbial biotechnology. Material and methods: The literature for this review was collected by searching leading scientific databases such as Embase, Medline/PubMed, Scopus, and [...] Read more.
Background: Developments in biology, genetics, soil science, plant breeding, engineering, and agricultural microbiology are driving advances in soil microbiology and microbial biotechnology. Material and methods: The literature for this review was collected by searching leading scientific databases such as Embase, Medline/PubMed, Scopus, and Web of Science. Results: Recent advances in soil microbiology and biotechnology are discussed, emphasizing the role of microorganisms in sustainable agriculture. It has been shown that soil and plant microbiomes significantly contribute to improving soil fertility and plant and soil health. Microbes promote plant growth through various mechanisms, including potassium, phosphorus, and zinc solubilization, biological nitrogen fixation, production of ammonia, HCN, siderophores, and other secondary metabolites with antagonistic effects. The diversity of microbiomes related to crops, plant protection, and the environment is analyzed, as well as their role in improving food quality, especially under stress conditions. Particular attention was paid to the diversity of microbiomes and their mechanisms supporting plant growth and soil fertility. Conclusions: The key role of soil microorganisms in sustainable agriculture was highlighted. They can support the production of natural substances used as plant protection products, as well as biopesticides, bioregulators, or biofertilizers. Microbial biotechnology also offers potential in the production of sustainable chemicals, such as biofuels or biodegradable plastics (PHA) from plant sugars, and in the production of pharmaceuticals, including antibiotics, hormones, or enzymes. Full article
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22 pages, 3103 KiB  
Article
Genomic and Metabolomic Analysis of the Endophytic Fungus Alternaria alstroemeriae S6 Isolated from Veronica acinifolia: Identification of Anti-Bacterial Properties and Production of Succinic Acid
by Farkhod Eshboev, Alex X. Gao, Akhror Abdurashidov, Kamila Mardieva, Asadali Baymirzaev, Mirzatimur Musakhanov, Elvira Yusupova, Shengying Lin, Meixia Yang, Tina T. X. Dong, Shamansur Sagdullaev, Shakhnoz Azimova and Karl W. K. Tsim
Antibiotics 2025, 14(7), 713; https://doi.org/10.3390/antibiotics14070713 - 16 Jul 2025
Viewed by 432
Abstract
Background: Endophytic fungi are prolific sources of bioactive metabolites with potential in pharmaceutical and biotechnological applications. Methods: Here, the endophytic fungus, Alternaria alstroemeriae S6, was isolated from Veronica acinifolia (speedwell), and conducted its anti-microbial activities, whole-genome sequencing and metabolome analysis. Results: The ethyl [...] Read more.
Background: Endophytic fungi are prolific sources of bioactive metabolites with potential in pharmaceutical and biotechnological applications. Methods: Here, the endophytic fungus, Alternaria alstroemeriae S6, was isolated from Veronica acinifolia (speedwell), and conducted its anti-microbial activities, whole-genome sequencing and metabolome analysis. Results: The ethyl acetate extract of this fungus exhibited strong anti-bacterial activity and the inhibition zones, induced by the fungal extract at 20 mg/mL, reached 16.25 ± 0.5 mm and 26.5 ± 0.5 mm against Gram-positive and Gram-negative bacteria. To unravel the biosynthetic potential for anti-bacterial compounds, whole-genome sequencing was conducted on A. alstroemeriae S6, resulting in a high-quality assembly of 42.93 Mb encoding 13,885 protein-coding genes. Comprehensive functional genome annotation analyses, including gene ontology (GO) terms, clusters of orthologous groups (COGs), Kyoto encyclopedia of genes and genomes (KEGG), carbohydrate-active enzymes (CAZymes), and antibiotics and secondary metabolites analysis shell (antiSMASH) analyses, were performed. According to the antiSMASH analysis, 58 biosynthetic gene clusters (BGCs), including 16 non-ribosomal peptide synthetases (NRPSs), 21 terpene synthases, 12 polyketide synthetases (PKSs), and 9 hybrids, were identified. In addition, succinic acid was identified as the major metabolite within the fungal extract, while 20 minor bioactive compounds were identified through LC-MS/MS-based molecular networking on a GNPS database. Conclusions: These findings support the biotechnological potential of A. alstroemeriae S6 as an alternative producer of succinic acid, as well as novel anti-bacterial agents. Full article
(This article belongs to the Section Fungi and Their Metabolites)
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21 pages, 1929 KiB  
Review
Antimicrobial Compounds from Anaerobic Microorganisms: A Review of an Untapped Reservoir
by Mamta Mishra, Upasana Sharma, Manisha Rawat, Harshvardhan, Shelley Sardul Singh and Suresh Korpole
Appl. Microbiol. 2025, 5(3), 68; https://doi.org/10.3390/applmicrobiol5030068 - 15 Jul 2025
Viewed by 385
Abstract
Anaerobes, the oldest evolutionary life forms, have been unexplored for their potential to produce secondary metabolites due to the difficulties observed in their cultivation. Antimicrobials derived from anaerobic bacteria are an emerging and valuable source of novel therapeutic agents. The urgent need for [...] Read more.
Anaerobes, the oldest evolutionary life forms, have been unexplored for their potential to produce secondary metabolites due to the difficulties observed in their cultivation. Antimicrobials derived from anaerobic bacteria are an emerging and valuable source of novel therapeutic agents. The urgent need for new antimicrobial agents due to rising antibiotic resistance has prompted an investigation into anaerobic bacteria. The conventional method of antimicrobial discovery is based on cultivation and extraction methods. Antibacterial and antifungal substances are produced by anaerobic bacteria, but reports are limited due to oxygen-deficient growth requirements. The genome mining approach revealed the presence of biosynthetic gene clusters involved in various antimicrobial compound synthesis. Thus, the current review is focused on antimicrobials derived from anaerobes to unravel the potential of anaerobic bacteria as an emerging valuable source of therapeutic agents. These substances frequently consist of peptides, lipopeptides, and other secondary metabolites. Many of these antimicrobials have distinct modes of action that may be able to go around established resistance pathways. To this effect, we discuss diverse antimicrobial compounds produced by anaerobic bacteria, their biosynthesis, heterologous production, and activity. The findings suggest that anaerobic bacteria harbor significant biosynthetic potential, warranting further exploration through recombinant production for developing new antibiotics. Full article
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27 pages, 1835 KiB  
Review
Investigating the Antimicrobial Activity of Anuran Toxins
by Manuela B. Pucca, Anne Grace A. C. Marques, Ana Flávia M. Pereira, Guilherme Melo-dos-Santos, Felipe A. Cerni, Beatriz C. S. Jacob, Isabela G. Ferreira, Rafael L. Piccolo, Marco A. Sartim, Wuelton M. Monteiro and Isadora S. Oliveira
Microorganisms 2025, 13(7), 1610; https://doi.org/10.3390/microorganisms13071610 - 8 Jul 2025
Viewed by 401
Abstract
Anurans, commonly known as frogs and toads, comprise a diverse group of amphibians distributed across all continents except Antarctica. This manuscript provides a detailed overview of the global anuran fauna, emphasizing their biology, remarkable adaptations, and ecological importance. A particular focus is placed [...] Read more.
Anurans, commonly known as frogs and toads, comprise a diverse group of amphibians distributed across all continents except Antarctica. This manuscript provides a detailed overview of the global anuran fauna, emphasizing their biology, remarkable adaptations, and ecological importance. A particular focus is placed on their specialized cutaneous glands, which are crucial for defense, communication, and survival. These glands secrete a diverse array of bioactive compounds, including peptides, alkaloids, and other secondary metabolites, shaped by evolutionary pressures. Among these compounds, toxins with potent antimicrobial properties stand out due to their ability to combat a broad spectrum of microbial pathogens. We explore the chemical diversity of these secretions, analyzing their modes of action and their potential applications in combating antibiotic-resistant bacteria and other pathogens. By integrating knowledge, this study underscores the importance of anurans as both ecological keystones and a valuable resource for biotechnological innovations. Furthermore, it highlights the urgent need to conserve anuran biodiversity for harnessing their potential in the development of novel antimicrobial agents to address global health challenges. Full article
(This article belongs to the Special Issue Exploring Antimicrobial Properties of Animal Toxins)
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26 pages, 2597 KiB  
Review
Strategies Used for the Discovery of New Microbial Metabolites with Antibiotic Activity
by Pablo Dasí-Delgado, Cecilia Andreu and Marcel·lí del Olmo
Molecules 2025, 30(13), 2868; https://doi.org/10.3390/molecules30132868 - 6 Jul 2025
Viewed by 672
Abstract
The discovery of new microbial metabolites is essential to combat the alarming rise in antimicrobial resistance and to meet emerging medical needs. This work critically reviews current strategies for identifying antimicrobial compounds, emphasizing the potential of microorganisms as a rich source of bioactive [...] Read more.
The discovery of new microbial metabolites is essential to combat the alarming rise in antimicrobial resistance and to meet emerging medical needs. This work critically reviews current strategies for identifying antimicrobial compounds, emphasizing the potential of microorganisms as a rich source of bioactive secondary metabolites. This review explores innovative methods, such as investigating extreme environments where adverse conditions favor the emergence of unique metabolites; developing techniques, like the iChip, to cultivate previously uncultivable bacteria; using metagenomics to analyze complex samples that are difficult to isolate; and integrates artificial intelligence to accelerate genomic mining, structural prediction, and drug discovery optimization processes. The importance of overcoming current challenges, such as replicating findings, low research investment, and the lack of adapted collection technologies, is also emphasized. Additionally, this work analyzes the crucial role of bacterial resistance and the necessity of a holistic approach involving new technologies, sustained investment, and interdisciplinary collaboration. This work emphasizes not only the current state of metabolite discovery but also the challenges that must be addressed to ensure a continuous flow of new therapeutic molecules in the coming decades. Full article
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20 pages, 1549 KiB  
Article
In Silico and In Vitro Characterization of Bacillus velezensis P45: Screening for a Novel Probiotic Candidate
by Carolini Esmeriz da Rosa, Cristian Mauricio Barreto Pinilla, Luiza Dalpiccoli Toss and Adriano Brandelli
Foods 2025, 14(13), 2334; https://doi.org/10.3390/foods14132334 - 30 Jun 2025
Viewed by 363
Abstract
Spore-forming Bacilli have been explored due to their potential biotechnological features and applications in human health and functional food research. This study focuses on the genetic and phenotypical characterization of the functional probiotic properties of Bacillus velezensis P45, a strain isolated from fish [...] Read more.
Spore-forming Bacilli have been explored due to their potential biotechnological features and applications in human health and functional food research. This study focuses on the genetic and phenotypical characterization of the functional probiotic properties of Bacillus velezensis P45, a strain isolated from fish intestines. B. velezensis P45 exhibited antimicrobial activity against Gram-positive and Gram-negative pathogens and demonstrated strong autoaggregation and biofilm formation properties in vitro. The strain also showed tolerance to gastrointestinal conditions and ability to metabolize and adhere to mucin. In silico analysis confirmed the absence of virulence factors and antibiotic resistance genes, reinforcing its safety as a probiotic candidate. Genome mining revealed the presence of genes related to adhesion, such as fibronectin-binding protein and enolases, and for the synthesis of secondary metabolites, including the antimicrobial lipopeptides fengycin, surfactin, and bacillibactin. In addition, phylogenetic comparison using the yloA (rqcH) gene associated with gut adhesion clustered strain P45 with other probiotic Bacillus and B. velezensis strains, while separating it from pathogenic bacteria. Thus, the strain B. velezensis P45 could be a valuable candidate as a probiotic due to its functional properties and safety. Full article
(This article belongs to the Special Issue Biosynthesis Technology and Future Functional Foods)
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32 pages, 18091 KiB  
Article
Yinchenhao Decoction Mitigates Cholestatic Liver Injury in Mice via Gut Microbiota Regulation and Activation of FXR-FGF15 Pathway
by Weiwei Li, Doudou Huang, Zichen Luo, Ting Zhou and Ziwen Jin
Pharmaceuticals 2025, 18(7), 932; https://doi.org/10.3390/ph18070932 - 20 Jun 2025
Viewed by 583
Abstract
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s [...] Read more.
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases. Full article
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22 pages, 3511 KiB  
Article
Genomic Characterization and Safety Evaluation of Enterococcus lactis RB10 Isolated from Goat Feces
by Nattarika Chaichana, Sirikan Suwannasin, Jirasa Boonsan, Thunchanok Yaikhan, Chollachai Klaysubun, Kamonnut Singkhamanan, Monwadee Wonglapsuwan, Rattanaruji Pomwised, Siriwimon Konglue, Rusneeta Chema, Manaschanan Saivaew and Komwit Surachat
Antibiotics 2025, 14(6), 612; https://doi.org/10.3390/antibiotics14060612 - 16 Jun 2025
Viewed by 582
Abstract
Background: The genus Enterococcus includes a diverse group of bacteria that are commonly found in the gastrointestinal tracts of humans and animals, as well as in various environmental habitats. Methods: In this study, Enterococcus lactis RB10, isolated from goat feces, was subjected to [...] Read more.
Background: The genus Enterococcus includes a diverse group of bacteria that are commonly found in the gastrointestinal tracts of humans and animals, as well as in various environmental habitats. Methods: In this study, Enterococcus lactis RB10, isolated from goat feces, was subjected to comprehensive genomic and functional analysis to assess its safety and potential as a probiotic strain. Results: The genome of E. lactis RB10, with a size of 2,713,772 bp and a GC content of 38.3%, was assembled using Oxford Nanopore Technologies (ONT). Genome annotation revealed 3375 coding sequences (CDSs) and highlighted key metabolic pathways involved in carbohydrate, protein, and amino acid metabolism. The strain was susceptible to important antibiotics, including ampicillin, chloramphenicol, tetracycline, and vancomycin, but exhibited resistance to aminoglycosides, a common trait in Enterococcus species with non-hemolytic activity. Genomic analysis further identified two intrinsic antimicrobial resistance genes (ARGs). The strain also demonstrated antimicrobial activity against Bacillus cereus DMST 11098 and Salmonella Typhi DMST 22842, indicating pathogen-specific effects. Key genes for adhesion, biofilm formation, and stress tolerance were also identified, suggesting that RB10 could potentially colonize the gut and compete with pathogens. Moreover, the presence of bacteriocin and secondary metabolite biosynthetic gene clusters suggests its potential for further evaluation as a biocontrol agent and gut health promoter. Conclusions: However, it is important to note that E. lactis RB10 was isolated from goat feces, a source that may harbor both commensal and opportunistic bacteria, and therefore additional safety assessments are necessary. While further validation is needed, E. lactis RB10 exhibits promising probiotic properties with low pathogenic risk, supporting its potential use in food and health applications. Full article
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23 pages, 6083 KiB  
Article
Functional Characterization, Genome Assembly, and Annotation of Geobacillus sp. G4 Isolated from a Geothermal Field in Tacna, Peru
by Alonso R. Poma Ticona, Karita C. R. Santos, Heber E. Ramirez-Arua, Roberto Castellanos, Jéssica Pinheiro Silva, Pedro R. Vieira Hamann, Eliane F. Noronha and Fabyano A. C. Lopes
Microorganisms 2025, 13(6), 1374; https://doi.org/10.3390/microorganisms13061374 - 13 Jun 2025
Viewed by 1619
Abstract
The genome of Geobacillus sp. G4, a thermophilic bacterium isolated from a geothermal field in Peru, was sequenced and analyzed to evaluate its taxonomic and biotechnological potential. This strain exhibits optimal growth at temperatures between 50 and 70 °C and at a pH [...] Read more.
The genome of Geobacillus sp. G4, a thermophilic bacterium isolated from a geothermal field in Peru, was sequenced and analyzed to evaluate its taxonomic and biotechnological potential. This strain exhibits optimal growth at temperatures between 50 and 70 °C and at a pH range of 6.0–7.5. Phenotypic assays demonstrated extracellular enzymatic activities, including amylases, cellulases, pectinases, and xylanases, highlighting its potential for efficient polysaccharide degradation. The assembled genome comprises approximately 3.4 Mb with a G+C content of 52.59%, containing 3,490 genes, including coding sequences, rRNAs, and tRNAs. Functional annotation revealed genes associated with key metabolic pathways such as glycogen and trehalose biosynthesis, indicating adaptation to carbohydrate-rich environments. Phylogenetic analyses based on ANI and dDDH values identified Geobacillus thermoleovorans KCTC3570 as its closest relative, suggesting a strong evolutionary relationship. Additionally, the genome harbors gene clusters for secondary metabolites such as betalactone and fengycin, suggesting potential industrial and pharmaceutical applications, including bioremediation. The identification of antibiotic resistance genes, specifically those conferring glycopeptide resistance, underscores their relevance for antimicrobial resistance studies. The presence of enzymes like amylases and pullulanase further emphasizes its biotechnological potential, particularly in starch hydrolysis and biofuel production. Overall, this research highlights the significant potential of Geobacillus species as valuable sources of thermostable enzymes and biosynthetic pathways for industrial applications. Full article
(This article belongs to the Special Issue Bioinformatics and Omic Data Analysis in Microbial Research)
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19 pages, 1037 KiB  
Review
Evolution and Functional Diversity of GATA Transcription Factors in Filamentous Fungi: Structural Characteristics, Metabolic Regulation and Environmental Response
by Danni Hu, Ruoyu Zhao, Yingxu Lin and Chunmiao Jiang
Microbiol. Res. 2025, 16(6), 120; https://doi.org/10.3390/microbiolres16060120 - 6 Jun 2025
Viewed by 629
Abstract
Filamentous fungi hold critical industrial value for their ability to produce enzymes, antibiotics, organic acids, and food fermentation. GATA transcription factors (TFs) serve as central regulators of nitrogen metabolism, synthesis of secondary metabolites, stress adaptation, and directly influence fungal development and pathogenicity in [...] Read more.
Filamentous fungi hold critical industrial value for their ability to produce enzymes, antibiotics, organic acids, and food fermentation. GATA transcription factors (TFs) serve as central regulators of nitrogen metabolism, synthesis of secondary metabolites, stress adaptation, and directly influence fungal development and pathogenicity in filamentous fungi. In this review, we primarily discuss the structural characterization, different types, and phylogenetic analysis of filamentous fungi GATA TFs in filamentous fungi. Subsequently, we systematically summarize the multifunctions of GATA TFs in the mycelial growth, morphological differentiation, and conidial development of filamentous fungi. In addition, we explore their functions in the synthesis of secondary metabolites such as antibiotics (e.g., cephalosporins, penicillins) and organic acids (e.g., ganoderic acid, fumaric acid) in filamentous fungi. Furthermore, we focus on the key roles of GATA TFs AreA and AreB in nitrogen and carbon metabolism in filamentous fungi and their potential synergistic regulatory relationships. Finally, we review the important roles of GATA TFs in the adaptation of filamentous fungi to environmental changes. This review provides research ideas for the development of genetically engineered strains with optimized growth characteristics, increased target metabolites in the fermentation production process, and enhanced environmental adaptability. Full article
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19 pages, 4294 KiB  
Article
Fermentation Products Originated from Bacillus subtilis Promote Hepatic–Intestinal Health in Largemouth Bass, Micropterus salmoides
by Kaifang Liu, Shubin Liu, Dexiang Feng, Pengwei Xun, Hanjun Jiang, Yanwei Zhang, Gaoliang Yuan and Xusheng Guo
Biology 2025, 14(6), 646; https://doi.org/10.3390/biology14060646 - 2 Jun 2025
Viewed by 614
Abstract
The fermentation product FP-WeiGuangSu is regarded as a novel, green and efficient antibiotic substitute. Such products constitute one of the principal strategies for addressing bacterial diseases in aquaculture in the future. This study investigates the effects of FPs derived from Bacillus subtilis on [...] Read more.
The fermentation product FP-WeiGuangSu is regarded as a novel, green and efficient antibiotic substitute. Such products constitute one of the principal strategies for addressing bacterial diseases in aquaculture in the future. This study investigates the effects of FPs derived from Bacillus subtilis on the antioxidant capacity and gut microbiota of Largemouth Bass (Micropterus salmoides). Experimental diets containing 0, 1%, 3% and 5% FPs (Control, H1, H2 and H3) were fed to M. salmoides. Although short-term administration of FPs exerted no significant influence on the growth performance of Largemouth Bass, serological findings demonstrated that supplementation with FPs decreased the contents of the liver injury markers ALT, AST and AKP, along with liver MDA content, and enhanced antioxidant capacity (SOD, CAT and GSH-px). Notably, the addition of 1% FPs significantly improved the systemic antioxidant performance (SOD, CAT, GSH-px and T-AOC). Moreover, the FP supplementation increased the expression levels of il-10 and IgM, and lipolysis-related genes. The results of gut microbiota analysis revealed that FPs significantly altered the diversity and structure of gut microbiota. The LEfSe results indicated that the microbial marker of the control group was Cetobacterium, those of the H1 group were Bacillus and Mycoplasma, those of the H2 group were Acinetobacter, Paenibacillus and g_unclassified_Rhizobiaceae, and that of the H3 group was Enterococcus. The most significant microbial marker upon the addition of FPs was Paenibacillus, and the pathways for biosynthesis of secondary metabolites, biosynthesis of antibiotics, and biosynthesis of amino acids were significantly activated. The Bugbase analysis results suggested that, compared with the control group, the abundance of anaerobic bacteria in the FP group decreased, while the abundance of microorganisms with mobile-element-containing and oxidative-stress-tolerant phenotypes increased. Hence, this study demonstrated that 1–3% FP dietary supplementation can be used to enhance antioxidant ability, and liver and intestine health of M. salmoides in the aquaculture industry and can be regarded as a promising feed additive in aquaculture. Full article
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52 pages, 8144 KiB  
Review
Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties
by Mulugeta Mulat, Riza Jane S. Banicod, Nazia Tabassum, Aqib Javaid, Abirami Karthikeyan, Geum-Jae Jeong, Young-Mog Kim, Won-Kyo Jung and Fazlurrahman Khan
Antibiotics 2025, 14(6), 555; https://doi.org/10.3390/antibiotics14060555 - 29 May 2025
Cited by 2 | Viewed by 954
Abstract
Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical [...] Read more.
Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical contexts such as device-associated infections and chronic wounds. Secondary metabolites derived from medicinal plants, such as alkaloids, tannins, flavonoids, phenolic acids, and essential oils, have gained attention as promising agents against biofilm formation, microbial virulence, and antibiotic resistance. These natural compounds not only limit microbial growth and biofilm development but also disrupt communication between bacteria, known as quorum sensing, which reduces their ability to cause disease. Through progress in nanotechnology, various nanocarriers such as lipid-based systems, polymeric nanoparticles, and metal nanoparticles have been developed to improve the solubility, stability, and cellular uptake of phytochemicals. In addition, the synergistic use of plant-based metabolites with conventional antibiotics or antifungal drugs has shown promise in tackling drug-resistant microorganisms and revitalizing existing drugs. This review comprehensively discusses the efficacy of pure secondary metabolites from medicinal plants, both as individuals and in nanoformulated forms or in combination with antimicrobial agents, as alternative strategies to control biofilm-forming pathogens. The molecular mechanisms underlying their antibiofilm and antivirulence activities are discussed in detail. Lastly, the current pitfalls, limitations, and emerging directions in translating these natural compounds into clinical applications are critically evaluated. Full article
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43 pages, 3579 KiB  
Review
The Multifaceted Health Benefits of Broccoli—A Review of Glucosinolates, Phenolics and Antimicrobial Peptides
by Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira, Celia Andrés Juan and Eduardo Pérez-Lebeña
Molecules 2025, 30(11), 2262; https://doi.org/10.3390/molecules30112262 - 22 May 2025
Viewed by 2862
Abstract
Broccoli, a highly valued Brassica vegetable, is renowned for its rich content of bioactive substances, including glucosinolates, phenolic compounds, vitamins, and essential minerals. Glucosinolates (GSLs), secondary plant metabolites, are particularly abundant in broccoli. The global consumption of broccoli has increased due to its [...] Read more.
Broccoli, a highly valued Brassica vegetable, is renowned for its rich content of bioactive substances, including glucosinolates, phenolic compounds, vitamins, and essential minerals. Glucosinolates (GSLs), secondary plant metabolites, are particularly abundant in broccoli. The global consumption of broccoli has increased due to its high nutritional value. This review examines the essential bioactive compounds in broccoli and their biological properties. Numerous in vitro and in vivo studies have demonstrated that broccoli exhibits various biological activities, including antioxidant, anticancer, antimicrobial, anti-inflammatory, anti-obesity and antidiabetic effects. This review analyzes several aspects of the chemical and biological activity of GSLs and their hydrolysis products, isothiocyanates such as sulforaphane, as well as phenolic compounds. Particular emphasis is placed on sulforaphane’s chemical structure, the reactivity of its isothiocyanate fraction (-NCS), and given the different behavior of SFN enantiomers, a wide and detailed review of the chemical synthesis methods described, by microbial oxidation, or using a chiral ruthenium catalyst and more widely using chiral auxiliaries for synthesizing sulforaphane enantiomers. In addition, the methods of chiral resolution of racemates by HPLC are reviewed, explaining the different chiral fillers used for this resolution and a third section on resolution using the formation of diastereomeric complexes and subsequent separation on achiral columns. Additionally, this review highlights the presence of antimicrobial peptides in broccoli, which have shown potential applications in food preservation and as natural alternatives to synthetic antibiotics. The antimicrobial peptides (AMPs) derived from broccoli target bacterial membranes, enzymes, oxidative stress pathways and inflammatory mediators, contributing to their effectiveness against a wide range of pathogens and with potential therapeutic applications. Full article
(This article belongs to the Special Issue Natural Antioxidants in Functional Food)
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15 pages, 2172 KiB  
Article
Structural Characterisation of TetR/AcrR Regulators in Streptomyces fildesensis So13.3: An In Silico CRISPR-Based Strategy to Influence the Suppression of Actinomycin D Production
by Karla Leal, Juan Machuca, Humberto Gajardo, Matías Palma, María José Contreras, Kattia Nuñez-Montero, Álvaro Gutiérrez and Leticia Barrientos
Int. J. Mol. Sci. 2025, 26(10), 4839; https://doi.org/10.3390/ijms26104839 - 19 May 2025
Viewed by 518
Abstract
The growing threat of antimicrobial resistance has intensified the search for new bioactive compounds, particularly in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, harbours a biosynthetic gene cluster (BGC) associated with actinomycin D production, an antibiotic with biomedical [...] Read more.
The growing threat of antimicrobial resistance has intensified the search for new bioactive compounds, particularly in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, harbours a biosynthetic gene cluster (BGC) associated with actinomycin D production, an antibiotic with biomedical relevance. This study investigates the regulatory role of TetR/AcrR transcription factors encoded within this biosynthetic gene cluster (BGC), focusing on their structural features and expression under different nutritional conditions. Additionally, we propose that repressing an active pathway could lead to the activation of silent biosynthetic routes, and our in-silico analysis provides a foundation for selecting key mutations and experimentally validating this strategy. Expression analysis revealed that TetR-279, in particular, was upregulated in ISP4 and IMA media, suggesting its participation in nutrient-dependent BGC regulation. Structural modelling identified key differences between TetR-206 and TetR-279, with the latter containing a tetracycline-repressor-like domain. Molecular dynamics simulations confirmed TetR-279’s structural stability but showed that the S166P CRISPy-web-guided mutation considerably affected its flexibility, while V167A and V167I had modest effects. These results underscore the importance of integrating omics, structural prediction, and gene editing to evaluate and manipulate transcriptional regulation in non-model bacteria. Targeted disruption of TetR-279 may derepress actinomycin biosynthesis, enabling access to silent or cryptic secondary metabolites with potential pharmaceutical applications. Full article
(This article belongs to the Special Issue CRISPR-Cas Systems and Genome Editing—2nd Edition)
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15 pages, 3170 KiB  
Article
Genome Mining Reveals Rifamycin Biosynthesis in a Taklamakan Desert Actinomycete
by Xinrong Luo, Zhanwen Liu, Xiaoxia Luo, Zhanfeng Xia, Chuanxing Wan, Haoxin Wang and Lili Zhang
Microorganisms 2025, 13(5), 1068; https://doi.org/10.3390/microorganisms13051068 - 3 May 2025
Viewed by 589
Abstract
Actinomycetes are recognized for producing diverse bioactive natural products, yet most biosynthetic gene clusters (BGCs) remain inactive under laboratory conditions. Rare actinomycetes from extreme environments represent underexplored reservoirs of metabolic potential. This study investigates Actinomadura sp. TRM71106, a rare actinomycete isolated from the [...] Read more.
Actinomycetes are recognized for producing diverse bioactive natural products, yet most biosynthetic gene clusters (BGCs) remain inactive under laboratory conditions. Rare actinomycetes from extreme environments represent underexplored reservoirs of metabolic potential. This study investigates Actinomadura sp. TRM71106, a rare actinomycete isolated from the Taklamakan Desert, through integrated genomic and metabolomic approaches. Genome sequencing revealed 45 secondary metabolic BGCs, including BGC38 showing 65% nucleotide similarity to the rifamycin BGC. Gene cluster networking and linear comparisons predicted its capacity to encode novel rifamycin analogs. Targeted activation strategies—overexpression of the pathway-specific regulator LuxR combined with metabolite isolation—mark the first activation of a rifamycin-like BGC in desert actinomycetes. This study highlights the untapped biosynthetic potential of rare actinomycetes in extreme environments and establishes Actinomadura sp. TRM71106 as a novel source for rifamycin production. These results provide a promising avenue for expanding the clinical pipeline of rifamycin-derived antibiotics. Full article
(This article belongs to the Section Environmental Microbiology)
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