Staphylococcus aureus is a major skin pathogen that causes a broad spectrum of infections, ranging from mild skin infections to severe invasive diseases. In this study, we evaluated antibacterial and antivirulence proper...Staphylococcus aureus is a major skin pathogen that causes a broad spectrum of infections, ranging from mild skin infections to severe invasive diseases. In this study, we evaluated antibacterial and antivirulence properties of selected FDA-approved skincare bioactives and antiseptics against multiple virulence factors. Minimum inhibitory concentration analysis of benzalkonium chloride, retinol, hydroquinone, and kojic acid showed strong antimicrobial activity at concentrations from 2 to 1024 µg/mL. Epigallocatechin gallate effectively inhibits biofilm formation by 81.53% and reduces staphyloxanthin production by 68.26%. Retinol exhibited antibiofilm activity, eradicating mature biofilm mass by 79.18%. Furthermore, a combination of skincare bioactives with antibiotics, including oxacillin, ciprofloxacin, tetracycline, and rifampicin, demonstrated synergy and additive effects, enhancing antibacterial efficacy. Molecular docking analysis exhibited strong predicted binding affinities of skincare bioactives and antiseptics against key virulence factors. This study highlights the multitarget antivirulence potential of skincare bioactives and antiseptics as an alternative strategy to mitigate diverse S. aureus infections.
This study aimed to isolate, characterize, and evaluate novel lactic acid bacteria (LAB) from local dairy products for their multifunctional probiotic potential, with a focus on cholesterol-lowering, antioxidant, and ant...This study aimed to isolate, characterize, and evaluate novel lactic acid bacteria (LAB) from local dairy products for their multifunctional probiotic potential, with a focus on cholesterol-lowering, antioxidant, and anti-inflammatory properties. A total of 24 raw milk and yogurt samples were collected, from which ten isolates were selected. In vitro assessment revealed significant cholesterol assimilation capacities ranging from 18.26% to 38.05%, with isolates NNY and HEY exhibiting the highest activity. These strains also demonstrated strong bile salt hydrolase (BSH) activity, high tolerance to simulated gastrointestinal conditions, resistance to phenol, broad-spectrum antimicrobial activity against foodborne pathogens, and favorable antibiotic susceptibility profiles. Both strains adhered effectively to Caco-2 cells and exhibited notable antioxidant (DPPH scavenging) and anti-inflammatory (albumin denaturation inhibition) activities. Scanning electron microscopy revealed distinct surface morphological changes supporting surface association of cholesterol with the bacterial cells. When applied in a high-fat cream matrix, the combined culture of HEY and NNY reduced cholesterol content by 11.4%, as validated by HPLC. Molecular identification via 16 S rRNA sequencing identified HEY as Lacticaseibacillus paracasei and NNY as Lacticaseibacillus chiayiensis. These findings highlight the potential of these indigenous LAB strains as multifunctional probiotics for cholesterol management and functional food development.
Antimicrobial resistance (AMR) remains one of the most critical global health challenges, demanding innovative therapeutics beyond conventional antibiotics. In this study, Pseudomonas aeruginosa strain KAEH25, isolated f...Antimicrobial resistance (AMR) remains one of the most critical global health challenges, demanding innovative therapeutics beyond conventional antibiotics. In this study, Pseudomonas aeruginosa strain KAEH25, isolated from rhizospheric soil in Menoufia, Egypt, was identified as a potent producer of 1-hydroxyphenazine (1-HPZ), a redox-active phenazine derivative exhibiting broad-spectrum antimicrobial activity. The compound was extracted, purified, and characterized by ultraviolet–visible (UV–Vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy (NMR), and gas chromatography–mass spectrometry (GC–MS), confirming its molecular identity and purity. To overcome its poor solubility and instability, 1-HPZ was encapsulated into mesoporous silica and magnetic Fe₃O₄ nanoparticles. Nanomaterials were synthesized and characterized using dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM), confirming nanoscale uniformity, high surface area, and successful drug loading. Molecular docking studies (Schrödinger 2023-4) revealed strong binding affinities of 1-HPZ toward key bacterial enzymes including topoisomerase IV (–7.909 kcal/mol), DNA gyrase (–6.650 kcal/mol), and RNA polymerase (–6.750 kcal/mol), implying multitarget inhibition of DNA replication, cell wall biosynthesis, and protein synthesis. Molecular dynamics simulations (Materials Studio 2024, COMPASS III) demonstrated favorable insertion energies (≈–4.8 × 10⁶ kcal/mol) for both free and nanoformulated 1-HPZ into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, indicating strong membrane affinity and potential for enhanced cellular uptake. Experimentally, the 1-HPZ-loaded mesoporous nanoparticles showed the most potent antibacterial effect, producing inhibition zones up to 25 mm against Listeria monocytogenes and Escherichia coli, surpassing free 1-HPZ. Time-kill and minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) assays confirmed bactericidal activity at low concentrations (MIC 4–16 µg/mL; MBC 8–32 µg/mL), outperforming both magnetic formulations and free 1-HPZ. These findings validate that mesoporous nanocarriers significantly enhance the solubility, stability, and antibacterial potency of 1-HPZ while maintaining biocompatibility. This integrated experimental and computational investigation demonstrates that coupling a microbial natural product with nanotechnology offers a promising route to overcome multidrug resistance. The 1-HPZ–mesoporous system provides a robust platform for next-generation antimicrobial therapies and magnetically guided drug delivery applications.
Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), continues to pose a major therapeutic challenge and highlights the need for alternative or supportive treatment strategies. In this study, the rec...Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), continues to pose a major therapeutic challenge and highlights the need for alternative or supportive treatment strategies. In this study, the recombinant iron-regulated surface determinant E (IsdE) protein was expressed, purified, and used to generate rabbit polyclonal IgG antibodies.Antibody specificity was confirmed by ELISA and Western blotting, and functional activity was assessed using an opsonophagocytic assay.To evaluate in vivo efficacy, BALB/c mice were challenged with a 5 × 10⁸ CFU dose of MRSA and treated with anti-IsdE IgG. Bacterial burden in internal organs was measured; histopathological changes and survival rates were recorded.To investigate the regulation of inflammatory responses by the immune system, levels of inflammatory cytokines (IL-6 and TNF-α) were measured in the serum of the studied mice.Treatment with anti-IsdE IgG was associated with reduced bacterial burden in target organs, decreased levels of inflammatory cytokines (IL-6 and TNF-α), improved histopathological findings, and increased survival compared with the control groups. However, vancomycin treatment produced the highest overall protection.These findings suggest that antibodies directed against IsdE may contribute to immune-mediated protection under experimental conditions and could be considered as a potential adjunctive strategy alongside antibiotic therapy, pending further validation.Further investigations are required to clarify antigen-specific mechanisms and to assess the translational potential of this approach.
The current paper presents a rational approach to design new selective and low-toxicity anti-breast cancer agents (a combination of amygdalin and mushroom-derived macrolides). This was done in order to address the effect...The current paper presents a rational approach to design new selective and low-toxicity anti-breast cancer agents (a combination of amygdalin and mushroom-derived macrolides). This was done in order to address the effect of cyanogenic toxicity of amygdalin besides improving its ability to target tumors. The library of 142 macrolide-amygdalin complexes was prepared and assayed using a multistage workflow of computations of field-based 3D-QSAR, molecular docking, state-of-the-art MM-GBSA calculations of free energies, computations of DFT/NBO, molecular dynamics (MD) simulations, and in-silico toxicity and hemolytic analyses. The 3D-QSAR models, which proved statistically strong (R2 = 0.86–0.99; Q2 = 0.70–0.73) showed that the steric and hydrophobic interactions were the most important determinants of the anticancer activity. The structure-activity analysis found B45, B46, B47, and B102 as the most active with large predicted pIC₅₀ values (5.05.8). A further molecular docking of the Cyclin D1-CDK4 (2W96), CDK6-V-cyclin (4TTH) showed higher binding affinities of the two complexes as compared to the FDA approved inhibitor Palbociclib, which established strong hydrogen bonds and hydrophobic interactions with key residues ASP129, HIS132, VAL234 and ASP233. MM-GBSA analysis obtained positive ΔG bind values (-55 to -65 kcal/mol), which validates stable binding energetics. The results of DFT and NBO suggested a high level of electronic delocalization, low HOMO-LUMO gaps, and high reactivity stability, whereas MD simulations showed no significant changes in RMSD and Rg during 100 ns, which confirmed the stability of conformations. Their non-toxic and biocompatible properties were confirmed by toxicity prediction of the ProTox-III server and hemolytic docking of oxy- and deoxyhemoglobin. Overall, the findings imply that the macrolide-amygdalin hybridization can be used to stabilize the cyanogenic group, increase the pharmacological selectivity, and serve as an excellent starting point towards the development of the next-generation CDK4/6-inhibitors against breast cancer.
Triterpenoid acids are secondary metabolites known to possess various beneficial biological activities. Their synthetic derivatives often display improved pharmacological properties and higher levels of efficacy. In this...Triterpenoid acids are secondary metabolites known to possess various beneficial biological activities. Their synthetic derivatives often display improved pharmacological properties and higher levels of efficacy. In this study, we investigated, the antibacterial effects of 13 synthesized oxime derivatives and 4 intermediates of betulonic and platanic acid, comparing them with those of the unmodified forms. Six Gram-positive pathogenic human bacteria, including four resistant strains from the genus Staphylococcus, were selected for testing together with two Gram-negative bacteria. All combinations of the prepared bacterial suspensions and 17 samples (500 − 62.5 µmol/L) were placed on 96-well microtitration plates. The microdilution method was used to measure the absorbance of the samples, from which bacterial growth curves were derived. Resazurin tests were performed to obtain fluorescence values and, thereby, determine the metabolic activity and bactericidal effects. The derivatives and intermediates exhibited higher sensitivity to the Gram-positive bacteria. The most effective samples, for which 90–100% growth inhibition was observed against resistant strains (S. aureus 368, S. epidermidis 335), were the oxime ester derivative of betulonic acid synthesized from 1-adamantylacetic acid (14; 500 µmol/L) and the C-3 acetate intermediate of platanic acid (18; 500 µmol/L). Sample 18 also showed 90–100% inhibition against S. aureus 670. Thus, our results suggest that the tested triterpenoid derivatives and intermediates have considerable potential for the development of new antibiotic therapies.
Lycopodium clavatum L., a well-known medicinal herb, grows luxuriantly in the eroding nutrient-poor mountain terrain of Darjeeling Himalaya. Rhizospheric microbiomes mediated growth and development for the plant has not...Lycopodium clavatum L., a well-known medicinal herb, grows luxuriantly in the eroding nutrient-poor mountain terrain of Darjeeling Himalaya. Rhizospheric microbiomes mediated growth and development for the plant has not been studied. This is the first report deciphering the cross-talk of the untapped rhizomicrobiome of L. clavatum. Three potential PGPR (plant growth promoting rhizobacteria) bacteria viz. Bacillus mycoides KUR1107, B. mycoides KUR1109 and Alcaligenes pakistanensis subsp. lycopodii KUR1110T* were identified based on 16S rRNA sequencing. The subsp. nov. has strong Indole-3-acetic acid (IAA) producing (150.66 ± 7.46 µg/ml), phosphate solubilizing (11.9 ± 0.21 µg/ml) and siderophore producing (99.1 ± 2.48 nmol/ml) property. It stimulates plant growth following root inoculation. Genome-wide data mining was performed for the unexplored A. pakistanensis subsp. lycopodii KUR1110 to find novel genes and metabolites. The genome of A. pakistanensis is ~ 3.99 Mb in size, with 3607 protein-coding genes. Genomic characterization gives a deeper insight into a repertoire of genes associated with antibiotic resistance, secondary metabolite biosynthesis, heavy metal resistance, IAA synthesis, and metabolism of sulfur, nitrogen and phosphorus. Production of inorganic phosphate solubilizing organic acids, siderophore biosynthesis precursors, and the compounds involved in defence were detected by Liquid chromatography-Mass spectrometry (LC-MS) analysis. In silico analysis of two key genes viz. di-iron N-oxygenase (dnfA) of dirammox pathway and lysine decarboxylase of siderophore biosynthesis revealed that the proteins were stable to execute their functions. A. pakistanensis subsp. lycopodii, contributing to global biogeochemical cycling, is a potential bioinoculant in nutrient-poor/heavy metal-infested soil and can be developed for sustainable bioremediation and biomining technology. [*NCBI accession no and MTCC deposit no for all three strains are B. mycoides KUR1107 (NCBI OR 592244, MTCC 13924), B. mycoides KUR1109 (NCBI OR592282, MTCC 13925), and A. pakistanensis subsp. lycopodii KUR1110T (NCBI OR592286, MTCC 13945)].
Biogenic selenium nanoparticles are a promising new branch of functional nanomaterials with attractive antimicrobial activity, antioxidant properties, and anticancer properties but their complete integrated characterizat...Biogenic selenium nanoparticles are a promising new branch of functional nanomaterials with attractive antimicrobial activity, antioxidant properties, and anticancer properties but their complete integrated characterization between synthesis, structure, molecular pathway, and safety has not fully been investigated. A rhizosphere Bacillus atrophaeus isolate was used in this research as an effective microbial nanofactory to produce highly uniform extracellular selenium nanoparticles. The resulting particles had a Z-average diameter of 126.4 ± 0.5 nm, a small polydispersity index of 0.145 and a stable negative surface charge of -32.5 mV. Biomolecular capping, amorphous structure, and spherical morphology were confirmed by physicochemical methods including UV-vis spectroscopy, TEM, SEM, XRD, and FTIR. The nanoparticles exhibited effective broad-spectrum antimicrobial effects with 16.5–24.2 mm bacterial and 22.0–39.3 mm fungal inhibition areas, and Aspergillus ochraceus was the most susceptible to the nanoparticles (39.3 mm). Assessment of antioxidants demonstrated a high radical scavenging ability with the IC50 equals 41.92 µg/mL, anticancer evaluation against HepG2 cells displayed dose-dependent cytotoxicity with the IC50 equals 94.71 µg/mL and also up to 77% cell viability reduction at a 200 µg/mL concentration. Molecular docking revealed that it interacts well with catalytic regions of bacterial DNA gyrase and fungal RNA polymerase in view of the antimicrobial mechanism observed. A positive forecast of safety margin, with no organ-level, mutagenic, carcinogenic, immunotoxic, and metabolic toxicity was predicted by in silico toxicity profiling. Taken altogether, the analysis of these results confirms that B. atrophaeus is a promising microbial system to be used in sustainable manufacturing of versatile selenium nanoparticles with an enormous therapeutic and biotechnological potential.
Species of the genus Hermatomyces (Pleosporales) are saprotrophic fungi associated with decaying wood and plant litter in tropical ecosystems. Although these species have been extensively studied in the previous decade,...Species of the genus Hermatomyces (Pleosporales) are saprotrophic fungi associated with decaying wood and plant litter in tropical ecosystems. Although these species have been extensively studied in the previous decade, their secondary metabolite profiles remain uninvestigated. During preliminary screening, cultures of several Hermatomyces species exhibited antifungal activity, indicating the presence of bioactive secondary metabolites and motivating further study.In this study, ethyl acetate extracts obtained from eight Hermatomyces species were screened for antimicrobial activity. Based on the observed activity, the ethyl acetate extract of H. reticulatus was selected for further chemical analysis and fractionated using preparative high-performance liquid chromatography. Structural elucidation of the isolated compounds was performed using nuclear magnetic resonance spectroscopy and X-ray crystallography.From the extract containing a complex mixture of metabolites, two known spiroketal compounds with documented antimicrobial activity, palmaromycins C2 and C12, were successfully identified. These compounds, previously reported from other fungal taxa, may contribute to the antifungal activity observed in Hermatomyces and suggest a potential ecological role of secondary metabolites in competitive interactions with other microorganisms. In addition, we provide a curated database of known palmarumycins and related compounds, compiled from published peer-reviewed structures, to facilitate future metabolite identification.
Sporisorium reilianum (S. reilianum) is a phytopathogenic fungus that infects Poaceae plants such as sorghum and maize. The sclerotium formed on sorghum, known as "Sphacelotheca sorghi(Link) Clint(S. sorghi)", is a tradi...Sporisorium reilianum (S. reilianum) is a phytopathogenic fungus that infects Poaceae plants such as sorghum and maize. The sclerotium formed on sorghum, known as "Sphacelotheca sorghi(Link) Clint(S. sorghi)", is a traditional resource with both medicinal and edible applications, valued for its purported effects in regulating menstruation, stopping bleeding, and protecting the liver. Although research on this fungus has increased significantly in recent years, a comprehensive academic review remains lacking. The limited number of existing reviews primarily focus on the perspective of plant pathology, missing an interdisciplinary integration encompassing microbiology, chemistry, and bioactivity. Therefore, this study provides a cross-disciplinary systematic review. At the microbiological level, it elaborates on six key areas: host specialization and adaptation, life cycle and infection process, pathogenic symptoms, effector proteins and molecular mechanisms, host defense, and genomic evolution. Chemically, it summarizes the major identified active components, including polysaccharides, steroids, alkaloids, melanin, and benzoic acid derivatives, amounting to a total of nine compounds. Regarding bioactivity, it reviews experimental evidence for its antioxidant, antitumor, anti-inflammatory, and anti-enteritis effects, alongside potential applications in areas such as anti-obesity and the development of functional foods and health products. This work aims to provide a foundational reference and forward-looking perspective to facilitate further research, resource development, and comprehensive utilization of this fungus.
Acinetobacter baumannii is a multidrug-resistant pathogen that causes serious nosocomial infections with limited therapeutic options. GuaB (Inosine Monophosphate Dehydrogenase, IMPDH) is an important target in purine bio...Acinetobacter baumannii is a multidrug-resistant pathogen that causes serious nosocomial infections with limited therapeutic options. GuaB (Inosine Monophosphate Dehydrogenase, IMPDH) is an important target in purine biosynthesis that has been identified as a promising target in anti-A. baumannii drug research. The dCBS regulatory domain of GuaB has been purposefully chosen for this research due to its role in allosteric regulation and structural dissimilarity with its human homologue. The integrated computational framework has been utilized to identify new GuaB inhibitors among marine fungal metabolites. The virtual screening of GuaB-dCBS with AutoDock Vina identified three lead compounds: CMNPD27312, CMNPD12442, and CMNPD28769. Density functional theory calculations were carried out to refine the structures of the ligands before redocking with GuaB-dCBS to evaluate their electronic compatibility with GuaB. The calculations showed good electronic compatibility with GuaB-dCBS compared to the positive control compound A1AUF. Long timescale molecular dynamics simulations of 500 ns were carried out to evaluate the stability of the ligand-GuaB-dCBS complexes. The structural stability of all ligand-GuaB-dCBS complexes has been shown in this research. The RMSD, RMSF, and hydrogen bond analysis showed that CMNPD27312 and CMNPD28769 have enhanced stability. The binding free energy calculations showed good ligand binding to GuaB-dCBS. The principal component analysis showed ligand-induced stability of GuaB-dCBS. The free energy landscape calculations showed ligand-induced stability of GuaB-dCBS. The QM/MM calculations showed good electronic compatibility of the ligands with GuaB-dCBS. The bioactivity prediction showed that CMNPD27312 and CMNPD28769 have high inhibitory potential (predicted pIC50 ≥ 7.2).
The helpful gut microbes create bioactive micro- and macromolecules known as postbiotics, which have substantial medical potential. These small-molecular-weight biomolecules, which provide the host with a number of physi...The helpful gut microbes create bioactive micro- and macromolecules known as postbiotics, which have substantial medical potential. These small-molecular-weight biomolecules, which provide the host with a number of physiological health advantages, are the subject of a revolutionary therapeutic strategy. Because of their varied delivery mechanisms and customizable dosage, several postbiotics are promising medical agents that may be used for both prophylactic and therapeutic purposes. Nonetheless, there are still a lot of obstacles to overcome when giving postbiotics in vivo. The current body of scientific literature supports utilizing targeted delivery systems based on nanoparticles as a novel and secure method for the delivery or/and release of postbiotics in a variety of (oral, intradermal, and intravenous) in vivo models due to their attractive characteristics in regards to low toxicity, high biodegradability, biocompatibility, and considerable capacity for carrying both hydrophobic and hydrophilic postbiotics. If postbiotics are to be widely used as therapeutic approaches, they must undergo considerable research and randomized double-blind clinical studies because they are still in the early stages of development. This article gives a thorough summary of the newest developments in drug delivery, with a focus on the main in vivo routes for the tailored delivery of postbiotics. However, the findings summarized in this review are primarily based on preclinical and early-stage studies, and limitations related to heterogeneous study designs, incomplete pharmacokinetic characterization, and limited clinical validation should be considered when interpreting the translational potential of postbiotic delivery systems.
This study aimed to evaluate colistin susceptibility and biofilm formation in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates and to compare planktonic minimum inhibitory concentrations (MICs) with...This study aimed to evaluate colistin susceptibility and biofilm formation in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates and to compare planktonic minimum inhibitory concentrations (MICs) with biofilm-associated minimum biofilm inhibitory concentrations (MBICs). A total of 105 non-duplicate CRAB isolates were analyzed. Colistin MICs were determined using broth microdilution, biofilm formation was quantified by crystal violet staining, and MBIC values were assessed using a resazurin-based biofilm susceptibility assay. Nine of 105 isolates (8.57%) were colistin-resistant under planktonic conditions, while all isolates were classified as weak biofilm producers, with mean OD₅₇₀ values of 0.1639 ± 0.021. MBIC values were significantly higher than corresponding MIC values (p < 0.0001), ranging from 16 to 128 µg/mL, with the majority of isolates (65.7%) exhibiting MBIC values of 64 µg/mL. Biofilm growth was associated with a marked increase in colistin concentrations required for inhibition in both colistin-susceptible and colistin-resistant isolates. Although MIC and MBIC values represent different growth conditions and are not directly comparable, the findings indicate that even weak biofilm formation is associated with substantially reduced colistin activity. These results suggest that reliance on planktonic MIC values alone may underestimate colistin response in biofilm-associated CRAB, and incorporation of biofilm-related parameters may improve the interpretation of antimicrobial susceptibility in these infections. These findings highlight the need for cautious interpretation of in vitro susceptibility data and support further investigation into biofilm-targeted therapeutic strategies.
Antimicrobial resistance (AMR) is a serious health concern of the 21st century, affecting millions of people globally. The current study employed a novel microbe-mediated method for synthesizing ZnO-based nanobiotics to...Antimicrobial resistance (AMR) is a serious health concern of the 21st century, affecting millions of people globally. The current study employed a novel microbe-mediated method for synthesizing ZnO-based nanobiotics to overcome AMR. An endophyte, Paenibacillus sp. strain IHC2, previously recovered from Indigofera heterantha root, was used as a source of green reductants and stabilizers to synthesize ZnO nanobiotics. These nanobiotics were then characterized using various spectroscopic methods, following which subjected to bioactivity evaluation against clinical drug-resistant bacterial pathogens and parasitic nematode, Caenorhabditis elegans. The UV-visible spectroscopy confirmed nanobiotic synthesis by showing a spectral peak at 395 nm. FTIR spectrum captured a range of organic functional groups (C–I, C–Br, C = C, C–O, C–H, O = C=O), from bacterial extract attached to the surface of the nanobiotics. The XRD analysis determined a spherical wurtzite morphology with a crystallite average size of 27.12 ± 7.16 nm. SEM images revealed polydispersed spherical nanobiotics and agglomerated morphologies with an average size of about 147.78 ± 34.71 nm. The EDX shows strong peaks at 1 eV and 8.7 eV for Zinc (65.53%) and a strong peak at 0.5 eV for Oxygen (7.08%). The antibacterial activities of the nanobiotic against clinical pathogens Staphylococcus aureus and Escherichia coli show zone of inhibition of 9.6 mm and 8.5 mm with an IC50 value of 4.08 and 5.66 mg/mL, respectively. The anti-nematodal activity of Paenibacillus sp. extract and ZnO nanobiotics against C. elegans shows an LD50 value of 113.35 ± 11.91 and 382.37 ± 5.40 µg/mL, respectively, after 24 h of exposure. Overall, we conclude that Paenibacillus sp. IHC2 extract mediated ZnO nanobiotics has moderate antibacterial and anti-nematicidal activities.
The global re-emergence of monkeypox virus (MPXV) has exposed a widening immunity gap following cessation of routine smallpox vaccination and renewed interest in next-generation orthopoxvirus vaccines. Unlike acute RNA v...The global re-emergence of monkeypox virus (MPXV) has exposed a widening immunity gap following cessation of routine smallpox vaccination and renewed interest in next-generation orthopoxvirus vaccines. Unlike acute RNA viruses, MPXV is a large double-stranded DNA virus with a dual-virion architecture intracellular mature virion (IMV) and extracellular enveloped virion (EEV) and encodes multiple immune evasion proteins that complicate vaccine design. These biological features necessitate multivalent antigen targeting and coordinated humoral and cellular immunity for effective protection. Messenger RNA (mRNA) vaccines provide a programmable, non-replicating platform capable of endogenous antigen expression and simultaneous targeting of conserved IMV and EEV structural proteins, including A29L, M1R, A35R, and B6R. In this review, we integrate current knowledge of MPXV immunobiology with advances in immunoinformatics and structural vaccinology to define rational design principles for multivalent mRNA constructs. We examine computational epitope mapping, structural validation, multi-antigen optimization strategies, and lipid nanoparticle–mediated delivery as enabling technologies for cross-clade and pan-orthopox coverage. Preclinical evidence demonstrates that multivalent mRNA vaccines induce robust neutralizing antibodies, Th1-biased CD4⁺ responses, and functional CD8⁺ T-cell activation in murine and early non-human primate models, with protection against lethal orthopoxvirus challenge. Comparative analysis with live-attenuated vaccinia and protein subunit platforms highlights the balance achieved by mRNA vaccines between endogenous antigen presentation and improved safety relative to replication-competent vectors. However, key scientific uncertainties remain, including long-term durability of plasma cell and memory T-cell responses, the influence of immunological imprinting in smallpox-vaccinated individuals, and resilience to antigenic evolution across MPXV clades. We discuss translational and regulatory considerations, immune correlates of protection, and the role of AI-driven structural optimization in next-generation vaccine refinement. Collectively, this review provides a mechanistically grounded framework for rational MPXV mRNA vaccine development and outlines the experimental and clinical priorities required to establish durable, broad, and adaptable orthopoxvirus immunity.
Lipids are essential biomolecules that play central roles in membrane structure, energy storage, and cellular signaling. During the past two decades, lipidomics has developed into a powerful analytical approach for syste...Lipids are essential biomolecules that play central roles in membrane structure, energy storage, and cellular signaling. During the past two decades, lipidomics has developed into a powerful analytical approach for systematic characterization of lipid composition, metabolism, and function across biological systems. Although early lipidomic studies focused primarily on animals and vascular plants, increasing attention has been directed toward microorganisms, whose lipid diversity reflects exceptional physiological and ecological adaptability across evolutionary timescales. This review focuses specifically on the comparative structural diversity of lipids across the main microbial groups – archaea, bacteria, yeasts, fungi, cyanobacteria, algae, and viruses—and on how mass spectrometry-based lipidomics has revealed adaptive strategies to environmental stress, temperature, salinity, pH, and availability of nutrients. Microorganisms exhibit pronounced variability in lipid structures and biosynthetic pathways. Archaeal membranes are characterized by ether-linked isoprenoid lipids that provide stability under extreme environmental conditions. In contrast, bacterial membranes contain diverse phospholipids, glycolipids, and hopanoids that enable rapid membrane remodeling in response to environmental stress. Fungi and algae synthesize characteristic sterols, glycolipids, and polyunsaturated fatty acids that are essential for membrane function, cellular signaling, photoprotection, and adaptation to fluctuating growth conditions. Recent advances in high-resolution mass spectrometry, particularly liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and ion mobility spectrometry, have enabled detailed profiling of complex microbial lipidomes and their dynamic responses to physiological and environmental stimuli. Integration of lipidomics with transcriptomic, proteomic, and metabolomic data further enhances understanding of lipid biosynthesis and regulation. This review demonstrates that microbial lipidomics provides valuable insights into microbial physiology and adaptation and supports applications in chemotaxonomy, and environmental microbiology.
Cadmium (Cd) contamination of agricultural soils presents a severe threat to global food security by impairing crop productivity and introducing toxins into the food chain. Seeking an effective and sustainable remediatio...Cadmium (Cd) contamination of agricultural soils presents a severe threat to global food security by impairing crop productivity and introducing toxins into the food chain. Seeking an effective and sustainable remediation strategy, this study investigated the synergistic potential of zinc ferrite nanoparticles (ZnFe₂O₄NPs) and plant growth-promoting rhizobacteria (PGPR; Citrobacter sp. NCCP-668) in enhancing cadmium stress tolerance and the productivity of okra (Abelmoschus esculentus). A pot experiment was designed employing two levels of Cd stress (30 µM and 60 µM), simulating conditions from moderately to highly contaminated soils. Ten distinct treatment groups were established, including controls, individual applications of ZnFe₂O₄ NPs (100 mg/L) and PGPR, and their combined application. The results unequivocally demonstrated that exposure to Cd stress alone significantly inhibited key germination metrics, vegetative traits, and anatomical features by 16% to 79% compared to the non-stressed control. However, the co-application of ZnFe₂O₄ NPs and PGPR significantly mitigated these deleterious effects. Under 30 µM Cd stress, the combined treatment increased the germination rate index by 125.3%, leaf area by 99%, and stomatal length by 130%. PGPR treatments, both individually and in combination, were particularly effective at enhancing moisture retention in vegetative tissues under Cd stress. These findings establish the co-application of ZnFe₂O₄ NPs and PGPR as a highly promising, eco-compatible strategy for the remediation of Cd-contaminated soils and the sustainable production of crops like okra, ensuring both food safety and security.
Morels (Morchella spp.) are highly valued edible and medicinal ascomycetes in temperate ecosystems, yet their taxonomy remains difficult because of marked morphological plasticity and the limited resolving power of singl...Morels (Morchella spp.) are highly valued edible and medicinal ascomycetes in temperate ecosystems, yet their taxonomy remains difficult because of marked morphological plasticity and the limited resolving power of single-locus markers. This study documents wild Morchella diversity from the Murree Hills, Pakistan, using an integrated morpho-cultural and molecular approach. Fifteen ascocarps collected from six localities during July-August 2024 were used for tissue isolation, yielding thirty-nine cultures, with multiple cultures recovered from individual ascocarps as independent isolation replicates. From these, nine representative isolates were selected for ITS-based sequencing and phylogenetic assessment. Culture recovery averaged 2.60 isolates per ascocarp, indicating successful establishment of cultures across sampling sites. Morphological and cultural observations supported the recognition of two principal forms: a pale morphotype assignable to the Esculenta clade (cf. Morchella deliciosa) and a darker morphotype affiliated with the Elata clade (within the Morchella elata complex). Bayesian ITS phylogeny and sequence-similarity comparisons supported this two-lineage pattern at the clade level. Because ITS alone is insufficient for confident delimitation of closely related Morchella species, these results should be regarded as preliminary lineage-level documentation rather than definitive species resolution. Nevertheless, this study provides baseline evidence for the occurrence of Esculenta- and Elata-affiliated morels in an understudied Himalayan region and establishes a foundation for future multilocus, population-level, and ecological investigations.
Damping-off disease, caused by the soil-borne oomycete Pythium irregulare, severely limits pea (Pisum sativum L.) production worldwide, highlighting the need for sustainable disease management strategies. This study eval...Damping-off disease, caused by the soil-borne oomycete Pythium irregulare, severely limits pea (Pisum sativum L.) production worldwide, highlighting the need for sustainable disease management strategies. This study evaluated the protective efficacy and immune-stimulatory potential of actinomycete-synthesized zinc oxide–boron oxide nanoparticles (ZnO–B₂O₃ NPs) against P. irregulare, compared with monometallic ZnO NPs, B₂O₃ NPs, Streptomyces gancidicus culture filtrate, and a reference chemical treatment. Infection by P. irregulare significantly reduced germination, growth, photosynthetic pigments, carbohydrate content, and indole-3-acetic acid (IAA) levels. All treatments mitigated disease symptoms and improved plant performance, with ZnO–B₂O₃ NPs providing the highest protection (88%) and effectively restoring biomass and yield attributes. Biochemical analyses revealed enhanced chlorophyll, carbohydrate levels, proline accumulation, and endogenous IAA in treated plants. Antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT), were upregulated, maintaining reactive oxygen species (ROS) homeostasis and reducing oxidative damage. Protein profiling (SDS-PAGE) confirmed restoration and induction of defense-related proteins. These findings provide mechanistic insights into nanoparticle-mediated immune modulation under oomycete stress and highlight the potential of actinomycete-derived ZnO–B₂O₃ nanoparticles as a sustainable approach to enhance pea immunity and productivity.
Paranasal sinus mycetoma, also known as a fungus ball, is a non-invasive fungal infection characterized by a dense conglomeration of hyphae within a sinus cavity, most commonly the maxillary and sphenoid sinuses. Diagnos...Paranasal sinus mycetoma, also known as a fungus ball, is a non-invasive fungal infection characterized by a dense conglomeration of hyphae within a sinus cavity, most commonly the maxillary and sphenoid sinuses. Diagnosis is primarily based on the typical finding of hyperdensities on computed tomography, but their precise chemical composition remains incompletely understood. The objective of our study was to investigate the detailed chemical composition of central compartments of mycetomas (grains) and the relationship between these chemical components and clinical and radiological findings. This prospective cohort study (7/2023–7/2025) included 44 mycetoma samples from 41 patients. During functional endoscopic sinus surgery, grains mycetoma samples were collected for histopathological, microbiological, and chemical analyses using electron microscopy coupled with spectroscopy. The mucosal and mycotic samples underwent histopathological examination using haematoxylin-eosin staining, periodic acid–Schiff staining, and Grocott methenamine silver staining. Microbiological analysis involved fungal cultures on Sabouraud’s agar, which were evaluated by a specialist after 6–14 days of incubation. Analysis was performed on 44 mycetoma findings – 34 mycetoma in maxillary sinus, 7 in sphenoid sinus, 1 in ethmoids and 2 multiple localisations. Chemical analysis revealed the presence of inorganic compounds in 93.2% of the samples. The most prevalent component was calcium phosphate. Other compounds were also identified, including barium sulphate and zinc oxide. It was found that all samples containing sulphates were located exclusively in the maxillary sinus. Although this clinical correlation was not statistically significant (p = 0.522) due to the small sample size, it strongly supports a odontogenic ethology for maxillary mycetomas. This study confirms the complex chemical composition of mycetomas, which is responsible for their characteristic radiological appearance. Sulphates were exclusively identified within the maxillary sinus, providing further characterization of these mycetomas. Detailed chemical analysis, therefore, represents a valuable tool for understanding the pathogenesis of this condition.