Two bacterial strains were isolated from root nodules of the chickpea plant (Cicer arietinum) in West Bengal and characterized to assess their potential for heavy metal (HM) tolerance and plant growth-promoting (PGP) attributes. Phylogenetic analysis based on the 16 S rRNA gene identified these strains, SMAJ_63 and SMAJ_180, belonging to the genera Enterobacter sp. and Labrys sp, respectively. The two strains were screened for tolerance to multiple HMs, including arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), and copper (Cu), with particular emphasis on chromium (Cr) due to its high environmental relevance and comparatively limited exploration in the literature. Two strains, SMAJ_63 and SMAJ_180, were evaluated for their tolerance to HMs, and their IC values were determined. PGP attributes, including phosphate solubilization, indole acetic acid (IAA), and ammonia production were determined. Strain SMAJ_63 exhibited IAA production of 23.29 µg/mL, whereas strain SMAJ_180 did not produce any detectable IAA. However, both strains were capable of producing ammonia, with strain SMAJ_63 and strain SMAJ_180 yielding 27.24 mM and 0.75 mM, respectively. Both strains demonstrated the ability to solubilize inorganic phosphate into soluble forms, indicating their potential contribution to enhanced phosphorus availability. Furthermore, strain SMAJ_63 exhibited exopolysaccharide (EPS) production, yielding 0.67 g/L, whereas strain SMAJ_180 did not produce any detectable EPS. In conclusion, these findings highlight the potential of the selected strains as effective PGP bacteria under heavy metal stress, indicating their applicability in enhancing crop productivity and contributing to sustainable agricultural practices.

Zearalenone contamination poses a continuing threat to food security and the health of the livestock industry; developing efficient, high-yield detoxifying enzyme formulations is therefore essential. This study aimed to achieve the high-level expression of zearalenone lactonohydrolase ZenG in Pichia pastoris. The resulting recombinant ZenG exhibited optimal activity at pH 8.0 and 50 °C, with a specific activity of 684 ± 2.17 U/mg. Replacing the α-factor signal peptide with the pre-Ost1-pro-α-factor signal peptide increased ZenG activity from 180.26 U/mL to 276.47 U/mL. Subsequent optimization of the gene dosage further boosted the yield to 479.52 U/mL. Co-expression of the molecular chaperones 100p-HAC and 55p-HAC1 elevated the enzyme activity to 557.85 U/mL and 582.01 U/mL, which correspond to 3.09-fold and 3.23-fold increases, respectively, compared to the initial G-α-ZenG strain. In conclusion, this study successfully constructed an engineered P. pastoris strain capable of highly efficient ZenG production, laying a solid foundation for its industrial-scale application.

Microplastics transport toxins, disrupt microbial and nutrient cycles, bioaccumulate to cause oxidative stress and endocrine disruption, jeopardizing ecosystems and human health. Despite understanding microplastic origins, distribution, and microbial degradation biotechnological remediation efforts remain fragmented and largely at the proof-of-concept stage. Recent high-throughput meta-omics has uncovered diverse plastisphere associated enzymes, while metabolic engineering platforms have demonstrated programmable biofilm trap-and-release mechanism and enzymatic upcycling of PET monomers; however, the translation of these technologies to diverse polymer classes and field applications is limited. Machine learning is emerging as a powerful tool to uncover efficient microplastic degradation strategies, a domain previously underexplored. This review critically synthesizes these interdisciplinary advances spanning microbial and enzymatic remediation evolution, metabolic-engineering architectures for capture and valorization, and AI-driven monitoring to identify persistent bottlenecks and propose a unified roadmap for deploying sustainable, biotechnology-driven solutions that can be scaled to address the global microplastic crisis. By bridging these domains, we aim to inform future research priorities and accelerate the translation of laboratory findings into industrial scale mitigation strategies.

One of the major uses of petroleum products is transportation fuel such as gasoline and diesel, consumption of which substantially contributes to global warming. Oleaginous microorganisms capable of growing on lignocellulose hydrolysates serve as sustainable alternatives to hydrocarbon derived fuels. Co-culturing of two oleaginous microorganisms Acinetobacter baylyi ADP1 and Lipomyces starkeyi Y-1389 potentially allow us to overcome limitations of each of them, i.e., a relatively low lipid productivity for the former and a sensitivity to lignin hydrolysate products of the latter. This study investigated the ability of L. starkeyi Y-1389 to produce lipids alone or in co-culture with A. baylyi ADP1, specifically examining the influence of lignin-derived inhibitors on this process. Microorganisms were cultured in a mineral medium supplemented with sugar mixtures (glucose and xylose) and non-sugar components (acetate, formate, furfural, 5-hydrox ymethylfurfural, p-hydroxybenzaldehyde, syringaldehyde and vanillin), which are typically produced during lignocellulose hydrolysis. Both microbes were shown to tolerate some levels of furfural (up to 0.5 g/l for yeasts and 0.1 g/l for bacteria), 5-hydroxymethylfurfural (up to 0.5 g/L for both), p-hydroxybenzaldehyde (up to 0.25 g/1 for bacteria and 0.5 g/ for yeasts), syringaldehyde (up to 0.5 g/l for both) and vanillin (up to 0.1 g/l for yeasts and 0.5 g/l for bacteria), which typically serve as potential growth inhibitors. Formate and acetate, also common components of lignocellulose hydrolysates, was shown to suppress lipid production in A. baylyi ADP1 but not L. starkeyi Y-1389. During 144 h fermentation all potential inhibitors as well as acetate and formate were completely consumed by co-cultures. While lipid content in co-culture (32-36% of dry biomass) was comparable to L. starkeyi Y-1389 monoculture (32-40%), without significant advantages observed for co-culture in terms of yield, the co-culture exhibited higher resistance to a lignin-derived inhibitor mix compared to the yeast monoculture. This suggests that A. baylyi ADP1 effectively detoxifies the medium, allowing for better overall performance under inhibitory conditions. The results also suggest that wood hydrolysates are more favorable for lipid production using the A. baylyi ADP1 and L. starkeyi Y-1389 co-culture than hydrolysates of herbaceous plants indicating that a co-culture is a better choice for biotechnological production of lipids when wood hydrolysate is used. Our findings indicate that despite bacterial dominance and suppression of A. baylyi lipid production by acetate and formate, the co-culture approach is a promising strategy for biotechnological lipid production, particularly when utilizing wood hydrolysates, warranting further investigation into optimizing these microbial consortia.

Lupinifolin possesses the capability to combat specific pathogenic bacteria. Nonetheless, Gram-negative bacteria exhibit minimal inhibition by lupinifolin. This study evaluated the synergistic antibacterial and antibiofilm activities of combinations of lupinifolin and antibiotics against pathogenic bacteria using a checkerboard assay and time-kill analysis. Crystal violet staining and confocal laser scanning microscopy (CLSM) were utilized to evaluate antibiofilm properties. After treatment, gene expression changes in isolates were evaluated using quantitative real-time PCR. Lupinifolin and streptomycin synergistically inhibited MRSA and VRE with a FIC index of 0.5, whereas lupinifolin and vancomycin similarly inhibited S. aureus ATCC25923. Partially synergistic interaction against E. faecalis ATCC29212 between lupinifolin and tetracycline, vancomycin, and chloramphenicol with an FIC index of 0.625, 0.5625, and 0.625, respectively. Partially synergistic interaction against E. faecium HTY0256 between lupinifolin and tetracycline with an FIC index of 0.625. The interaction between lupinifolin and streptomycin against Gram-negative bacteria, such as E. coli ATCC25922, showed a synergistic effect. The time-kill assay of the combinations showed an inhibitory effect of more than 3 log and 2 log (CFU/ml) at 4 h incubation. CLSM revealed that the combinations reduced biofilm formation. The combination of lupinifolin and streptomycin altered biofilm-forming genes in E. faecalis ATCC29212 and VRE isolates; gelE and bepA were down-regulated. In contrast, MRSA isolates had sarA and ebpS up-regulated. In addition, our findings suggested that lupinifolin destroys cell membranes, as demonstrated by the expression of secA. Our investigation enabled the prospective integration of lupinifolin with antibiotics, enhancing their efficacy and application against antimicrobial-resistant pathogens.

Acne is a common dermatological condition that requires novel therapeutic strategies. Probiotics, live microorganisms that confer health benefits, have emerged as a promising option for acne management. This review summarizes current evidence on the role of probiotics, focusing on their ability to modulate the skin microbiota, reduce inflammation, and influence the skin-gut axis. Both oral and topical probiotic applications have shown potential-oral formulations primarily act through gut-skin immune modulation, whereas topical preparations directly target the cutaneous microbiota and local inflammation. Certain strains demonstrate antimicrobial activity against acne-associated bacteria, offering a targeted approach. Their use alongside conventional therapies and the development of topical formulations further expand treatment possibilities. As a personalized and well-tolerated intervention, probiotics have the potential to improve acne outcomes and enhance patients' quality of life. However, clinical evidence is limited by the scarcity of large randomized controlled trials, and further studies are needed to confirm efficacy and optimize treatment protocols. Future research should prioritize strain-specific recommendations, dosage optimization, and integration with precision dermatology.

Helicobacter pylori (H. pylori) is a widespread pathogen and a significant causative agent of chronic gastritis and peptic ulcers. However, eradication rates are declining rapidly because of increasing antibiotic resistance, and recurrence rates are rising. Quinolone-based regimens were once considered effective treatment options; however, their clinical utility has been substantially limited in recent years by a marked increase in resistance rates worldwide. Therefore, the development of more effective drugs and treatment strategies is crucial for combating H. pylori infections. This study evaluated the in vitro antibacterial activity and cytotoxicity of a series of novel quinolone compounds (provided by the team of Professor Ying-Qian Liu from the School of Pharmacy, Lanzhou University), ultimately identifying two lead compounds, ET-8 and ET-30, for further investigation, with minimum inhibitory concentrations (MICs) of 5.29 micromolar (µM) and 5.20 µM, respectively. Furthermore, ET-8 and ET-30 were also effective against both sensitive and resistant strains of H. pylori. Investigations involving urease inhibition assays, transmission electron microscopy, and adhesion assays suggested that ET-8 and ET-30 likely exert their antibacterial effects by disrupting bacterial morphology, inhibiting adhesion and colonization, and suppressing urease activity. Additionally, RT‒qPCR analysis revealed that these phenotypic changes were accompanied by the downregulation of key virulence and adhesion genes (vacA, cagA, sabA, and babA); however, this correlation does not establish causation, providing a compelling mechanistic hypothesis for the observed antibacterial effects. Collectively, these findings demonstrate that compared with the current fluoroquinolone therapeutic, levofloxacin (LEV), ET-8 and ET-30 exhibit superior antibacterial activity and a more favorable safety profile, highlighting their strong potential as candidate agents for future anti-H. pylori therapies.

Pretomanid, a novel nitroimidazoles or nitroimidazooxazines, was recently approved as part of BPaL (Bedaquiline, Pretomanid, and Linezolid) regimen for treating extensively drug-resistant (XDR) and treatment-intolerant/ nonresponsive multidrug-resistant (MDR) cases of pulmonary tuberculosis (TB). It offers new hope in the global fight against drug-resistant TB, which remains a major health challenge. However, the pursuit of better treatment outcomes has been confronted by the rapid emergence of resistance to these drugs. Resistance to pretomanid has been documented in both laboratory and clinical isolates of Mycobacterium tuberculosis. The identification of pretomanid-resistant strains of Mycobacterium tuberculosis highlights the need for judicious use, continuous surveillance and monitoring of pretomanid resistance in TB control programs to prevent further resistance development and ensure the continued success of pretomanid in treating drug-resistant TB. Although genetic mutations associated with pretomanid resistance have been identified in key genes such as ddn and fgd1 of Mycobacterium tuberculosis, the insights into the molecular mechanisms of pretomanid resistance are still quite limited. The better understanding of resistance patterns and molecular mechanisms underpinning pretomanid resistance is crucial for the establishment of uniform phenotypic DST methods and the development of molecular tools for rapid identification/ surveillance of pretomanid resistance. The present review explores the role of pretomanid in treating MDR and XDR-TB cases and provides an updated overview of the pharmacological properties, mechanisms of action, clinical efficacy, and the impact of resistance on the long-term effectiveness of pretomanid in TB treatment regimens.

Persistent organic pollutants (POPs) are harmful chemicals that resist degradation and remain in the environment for a long time. These pollutants originate from various sources, such as industrial, agricultural, and waste disposal. They contaminate the environment and adversely affect human health. Bioremediation is an eco-friendly process for reducing the toxicity of POPs to both the environment and living organisms. Anaerobic degradation has emerged as a viable strategy for eliminating these persistent chemicals from the environment while also playing a significant role in mitigating climate change. Introducing POPs into the environment contributes to global warming and disturbs the Earth's natural systems. Nevertheless, increasing temperature promotes the microbial degradation of POPs by microbial communities in natural ecosystems. Integrating Artificial Intelligence with bioremediation strategies can enhance POP degradation. This review offers a comprehensive analysis of the effects of climate change-related factors, such as temperature variations, redox changes, and hydrological modifications, on the microbial degradation kinetics and pathway efficiency of POPs in sulfate-reducing, methanogenic, iron-reducing, and denitrifying environments. According to quantitative evaluations of recent research, whereas drastic changes may inhibit community stability, moderate warming might boost microbial activity and accelerate breakdown rates by up to 50%. Overall, this review provides important insights for sustainable POP management in a warming world by advancing a comprehensive framework that connects the effects of climate change with anaerobic microbial pathways.

Morganella morganii exemplifies a typical case of an open pangenome, where genes move intra- and interspecies via horizontal gene transfer. Through pangenome analysis, the study maps three agriculture isolates; M. morganii with strong plant growth promoting (PGP) activity, along with 78 publicly available genomes from clinical, food, wastewater, and animal sources. The analysis showed 20,860 gene clusters with only 9.99% core genes and a discriminating distribution of 75.20% cloud genes across different niches. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed 33, 36, and 38 genes related to nutrient solubilization in M. morganii isolates HM01, HM02, and HM03, respectively. Chemotaxis genes, crucial for stress response, were most abundant in HM03 (30), followed by HM01 (17) and HM02 (27). Additionally, numerous biosynthetic gene clusters encoding antibacterial and antifungal metabolites were identified. Clinical and wastewater isolates harboured a higher number of mobile genetic element (MGE) linked antimicrobial resistance (AMR) genes that confer resistance to 15 antibiotic classes. These AMR genes were predominantly plasmid-borne and found to transfer in M. morganii from clinical pathogens such as E. coli and A. baumannii. This study indicates that habitat pressure creates the scenario for selection of functional traits which enables the ecosystem specific survival of M. morganii. Together, the present investigation provides important insight into the genomic diversity and remarkable PGP potential of M. morganii strains for sustainable agriculture. The pangenome analysis proposes that detailed investigation is needed to confirm their efficacy as PGP bacteria and to distinguish them from pathogenic strains.

The occurrence of microcystins in freshwater bodies is a global concern as they pose possible health effects on aquatic life, humans, wildlife and livestock. In a continued drive to find technologies for their safe removal from water, biodegradation has been identified as one of the effective, low cost and safe technologies. Using classic batch culture experiments, this work identified a bacterial consortium obtained from abattoir effluents, that could metabolize microcystin-LR (MC-LR) as the sole source of carbon. After 21 days of incubation the MC-LR concentrations (3 mg L) were reduced by 57% due to biological activities. The composition of the bacterial consortium was determined from 16 S rRNA gene sequencing and 20 dominant genera were identified. Among the 20 dominant genera identified, five (Stenotrophomonas, Aeromonas, Alcaligenes, Morganella and Citrobacter) are known MC-LR degraders. The remaining genera have not previously been reported to degrade MC-LR. These taxa may represent novel MC-LR-degrading bacteria, or alternatively, they may play supportive roles in the consortium without directly participating in MC-LR degradation. Hence their exact role needs to be established. Compared to the indigenous abattoir effluent bacterial communities, the MC-LR degrading consortium exhibited improved metabolic potentials as measured by their ability to metabolize a set of 31 different carbon substrates. Overall, these results confirm the ubiquitous distribution of microcystin degraders and further highlight industrial effluents as potential sinks for biotechnological tools for environmental bioremediation. Nonetheless, further work to optimize the degradation reaction, identify the role and pathogenicity of each individual bacterium as well as identify the genes involved remain crucial to cement possible future applications of this bacterial assemblage.

This study investigated the antifungal mechanisms of geraniol against Candida albicans. Geraniol significantly inhibited growth and biofilm formation, with a minimum inhibitory concentration (MIC) of 0.5 µL/mL. At concentrations of 0.3, 0.45, and 0.6 µL/mL, geraniol substantially reduced biofilm biomass (P < 0.05). Microscopic analyses revealed apoptosis induction, membrane shrinkage, and structural damage. Mechanistically, geraniol disrupted cell membrane permeability, inhibited ergosterol synthesis, and downregulated the expression of key virulence genes (SAP5, SAP6, SAP7). These multifaceted mechanisms highlight geraniol as a promising antifungal candidate with potential clinical relevance in combating antifungal resistance. Future studies should include vivo validation to explore its therapeutic application.

Microorganisms remain a prolific source of bioactive compounds, yet discovery efforts are often hindered by traditional methods and the repeated isolation of known molecules. In the post-genomics era, advances in genome mining and multi-omics technologies have revealed the hidden potential of biosynthetic gene clusters. A major challenge, however, lies in reliably linking these gene clusters to their metabolites and in the activation of silent pathways. This review summarizes recent breakthroughs addressing these challenges, focusing on the most recent case studies (up to 2025), and covering three interconnected themes. First, it reviews the current strengths and limitations of microbial genomics and artificial intelligence in natural product discovery, emphasizing different genome-guided discovery strategies and the emerging applications of artificial intelligence. Second, it highlights strategies for activating silent gene clusters, covering both untargeted and targeted approaches. Third, it discusses the expansion of chemical diversity through bioprospecting in underexplored ecological niches, the integration of sustainable, ethically informed practices, and the development of novel cultivation platforms. By synthesizing these advances, this review provides a forward-looking perspective, proposing how the integration of current tools in one framework can establish a predictive and potentially highly efficient method for linking biosynthetic gene clusters to their metabolites. Such integrative approaches may accelerate the discovery of microbial natural products and contribute sustainable solutions to global health challenges, including antimicrobial resistance. In conclusion, this review represents an up-to-date roadmap for researchers in microbial natural product research from a biological perspective, identifies existing strengths and knowledge gaps, and highlights promising, proof-of-concept strategies that can drive future advances in the field.

Canine distemper is a highly contagious disease of domestic dogs and various species of wild animals, and is associated with high mortality. It is caused by canine morbillivirus (formerly known as CDV or canine distemper virus), a member of the Morbillivirus genus under Paramyxoviridae family. The disease is endemic in many parts of the world, including India. For effective control of the disease, reliable diagnostic tools are of utmost importance. The circulating CDV strains in India belong to a novel "India1/Asia-5" lineage, highlighting the need for the development of new diagnostic tools. The nucleocapsid (N) protein is the major structural protein and one of the most immunogenic proteins of the virus; thus, it has been the preferred diagnostic target. Therefore, the present study was aimed at expressing the nucleocapsid protein of CDV using the baculovirus expression system in insect cells and its successful purification using affinity column chromatography. Expression and specificity of the recombinant N protein were confirmed using SDS-PAGE and Western blot analysis, revealing a band of approximately 58 kDa. The purified protein also reacted with CDV polyclonal serum, suggesting that the N protein was expressed in an immunoreactive form. Among the panel of monoclonal antibodies generated against CDV, only CDV-2F8 exhibited specific reactivity with the recombinant N protein, indicating the preservation of at least one linear epitope. The diagnostic suitability of the expressed protein was further confirmed by using it as a coating antigen in an indirect ELISA, which clearly distinguished between CDV-positive and negative dog serum samples. The recombinant N protein developed in the present study can facilitate large-scale field application of recombinant protein-based diagnostics for CDV, as it eliminates the need for live virus antigen in routine serodiagnostic assays.

Rapid industrialisation, urbanisation, and agricultural chemical fertilizer expansion have raised concerns over the accumulation and biomagnification of recalcitrant and emerging contaminants. Often, these compounds are resistant to degradation, and their conversion may lead to generation of even more toxic derivatives, which ultimately makes their remediation a crucial environment concern. Conventional treatment techniques are often considered expensive, inefficient and harmful to the environment; therefore the necessity to shift towards sustainable alternatives is required. Microalgae have emerged as a promising tool for bioremediation, offering cost-effective and eco-friendly solutions. Using microalgae as sustainable approach will not only remove toxic pollutants but also enable the generation of biomass that has numerous applications. Microalgae degrade the pollutants by using biosorption, bioaccumulation, biotransformation, biodegradation, and photodegradation and use their byproducts for their own growth. This review mainly addresses and critically examines the potential of microalgae-based bioremediation processes for eliminating persistent and newly discovered toxic contaminants. For example, Microspora amoena, Cladophora. glomerata, Enteromorpha intestinalis removes heavy metal chromium by the biosorption process with a removal capacity of 66.6%. Like that, microalgae have various species that have remarkable potential of removing pharmaceuticals, dyes, hydrocarbons, pesticides and plastic waste by using mechanisms like biosorption, bioaccumulation, biodegradation, biotransformation and photodegradation. They also have various applications in wastewater treatment and new developments in the phycoremediation process. This review paper also emphasizes on emerging technologies, mechanisms and potential sustainable environment solutions for the future. It may also serve as a feasible door for future research focusing on microalgae and their applications.

The escalating global threat of antimicrobial resistance necessitates the exploration of sustainable natural sources such as cyanobacteria for antioxidant and antimicrobial compounds. In this study, three hot-spring dwelling cyanobacterial strains- Mastigocladus ambikapurensis TA-9, Desikacharya sp. TPB-4 and Westiellopsis sp. TPR-29 were investigated for their bioactive potential. Among these, TPB-4 exhibited the highest total phenolic and flavonoid contents along with strong free-radical scavenging activity. The methanolic extract of TPB-4 demonstrated antimicrobial effects. TLC-purification followed by HR-LCMS analysis revealed caffeic acid as one of the major active constituents. The mechanistic investigations with caffeic acid showed multiple antimicrobial targets including disruption of bacterial (Aeromonas) outer membranes, cell wall integrity and central dogma as evidenced by FTIR and proteomic analyses. These findings highlight the potentiality of hot-spring isolates as natural repositories of bioactive polyphenols, role of proteomics in elucidating antimicrobial targets and suggested caffeic acid as a promising candidate for developing natural antimicrobial therapeutics.

Postbiotics, defined as microbial metabolites, confer health and nutritional benefits. Postbiotics, which are a step beyond probiotics, have emerged as a promising alternative to live microbial cells. While offering stability and safety, postbiotics improve efficacy and avoid the risks associated with live microorganisms. Key metabolite substances such as bacteriocin, peptides, and exopolysaccharides exhibit biological activities, thereby improving food preservation and functional enhancement. This comprehensive review aims to provide know-how for postbiotics' technological, functional, and health-promoting applications across various food systems. Advanced transport mechanisms for delivering postbiotics, such as encapsulation, nanoemulsions, and microfluidic microspheres, have created effective postbiotic delivery systems (PDS). Despite significant progress, mechanistic understanding, production standardization, and regulatory frameworks are still not well understood. Therefore, in-depth research into transport mechanisms and global compliance standards will ensure safe and reproducible applications of postbiotics. Future innovations that integrate agro-industrial by-product bioconversion, advances in omics technologies, and AI-assisted modeling will further support the circular bioeconomy, optimization, and functional prediction from a sustainability perspective.

Avermectins, macrocyclic lactones produced by Streptomyces avermitilis, serve as essential therapeutic and agrochemical agents. LuxR-type transcriptional regulators are multifunctional proteins known to orchestrate antibiotic biosynthesis alongside virulence modulation, biofilm dynamics, and host immune interactions. However, no prior studies have characterized LuxR-family proteins as direct regulators of avermectin biosynthesis. This study delineates the mechanism through which SAV111, a LuxR-family transcriptional activator, enhances avermectin biosynthesis. Batch fermentation of the SAV111-overexpressing strain demonstrated dual functionality: (1) significant upregulation of avermectin titers and (2) accelerated hyphal growth kinetics. Developmental profiling revealed precocious morphological differentiation in the overexpression strain compared to wild-type controls. Electrophoretic mobility shift assays confirmed direct binding of SAV111 to the aveA1 promoter, encoding the synthase catalytic subunit within the pathway of avermectin biosynthetic. Transcriptional activation of aveA1 represents the primary mechanism underlying SAV111-mediated avermectin overproduction. These findings advance the understanding of LuxR-family regulatory networks in secondary metabolism and establish a molecular framework for engineering hyperproductive S. avermitilis strains.

Biofilms are organized microbial communities that are surrounded by a matrix of extracellular polymeric substance (EPS), which raises significant challenges to environmental, and medical applications. Their intricate architecture and adaptive behavior enable them to resist conventional antimicrobial therapies, primarily due to restricted drug diffusion, altered metabolic activity, and the emergence of resistance mechanisms. To address these challenges, synthetic drug-based strategies have emerged, focusing on the disruption of key stages in biofilm development, such as bacterial adhesion, quorum sensing (QS), EPS production, and biofilm maturation. Quorum sensing inhibitors, including synthetic furanones, peptide-based inhibitors, and nanoparticles, have shown promising results in interfering with biofilm signaling pathways and preventing biofilm maturation. EPS matrix, such as chelating agents and enzymatic treatments, weaken the biofilm matrix, rendering the microbial cells more susceptible to antimicrobial agents. Nanotechnology-driven approaches, utilizing metal nanoparticles, functionalized nanoparticles, and nanocarrier-based drug delivery systems, enhance. These strategies enhance antimicrobial penetration and efficacy while reducing off-target effects; however, clinical translation is limited by cytotoxicity, pharmacokinetic constraints, and microbial adaptation. Future work should prioritize multi-targeted therapies, personalized biofilm disruption, and advanced drug delivery systems to combat biofilm-related infections and industrial biofouling.

Biofilm formation and antimicrobial resistance (AMR) are critical global health concerns, necessitating the discovery of novel therapeutic compounds. Enterococcus gallinarum, an opportunistic pathogen intrinsically resistant to vancomycin, is responsible for severe infections, often leading to endocarditis, bloodstream dissemination, immune dysregulation, and tissue damage. The limited efficacy of existing treatments underscores the urgent need for alternative therapeutic strategies. Recently, we reported the efficacy of 4,5,7-trihydroxyflavanone (THF) as an exhibited potential antimicrobial agent. In this study, the antibiofilm activity of THF against E. gallinarum was examined. In addition, the role of THF in preventing infection and mortality in zebrafish was also analysed using histopathological studies. The host-drug interaction was investigated through a network pharmacology approach for bacterial endocarditis. The top hub genes found in this analysis were docked with THF using the Glide XP protocol, and simulations were performed by GROMACS version 2020. The results suggest the potential of THF in inhibiting bacterial adhesion to extracellular matrix (ECM) and the disruption of mature biofilms. The histopathological results showed significantly recovered tissues after THF treatment. Furthermore, the network pharmacology studies of bacterial endocarditis disease revealed the identification of top hub genes MMP-2 and MMP-9, which have the function of binding to ECM and causing inflammation. The molecular docking and dynamics simulations performed between MMP-2 & MMP-9 showed a strong binding score of -4.652 kcal/mol & -7.597 kcal/mol between THF and MMP-2 & MMP-9, suggesting the anti-inflammatory potential of THF as well. This significant influence on host-pathogen interactions, particularly in modulating immune responses and inflammation, makes it a promising drug candidate for bacterial infections and necessitates its consideration for future research and studies.