Archives of Microbiology最新文献

The sporicidal mechanism of high-pressure thermal sterilization (HPTS) combined with muramidase against Bacillus subtilis spores was investigated. Results demonstrated that HPTS at 600 MPa/75°C with 0.3% muramidase achieved a 6.09 log reduction in Bacillus subtilis spores. The combined processing significantly increased the leakage of protein, nucleic acid, and dipicolinic acid, while significantly reducing Na⁺/K⁺-ATPase activity (P < 0.05). Scanning electron microscopy revealed notable morphological changes in spores after combined processing. A significant increase in propidium iodide (PI)-infiltrated spores indicated enhanced spore inner membrane permeability (P < 0.05). molecular composition analysis further showed disordered arrangement of fatty acid acyl chains, structural alterations in nucleic acids and proteins, and increased the peptidoglycan layer flexibility. These findings provided insights into the sporicidal mechanism of HPTS combined with muramidase.

Bacterial meningitis (BM) can lead to cognitive impairment, seriously affecting patients’ quality of life. Our previous study demonstrated a significant increase in procalcitonin (PCT) levels in cerebrospinal fluid (CSF) in BM patients, but the functional implications remain unknown. We found high expression of PCT in the hippocampus of LPS-induced neuroinflammation models. PCT had a neurotoxic effect on the primarily cultured hippocampal neurons. The high dose of PCT induced neuronal apoptosis. The low dose of PCT impaired the arborization of hippocampal neurons and reduced the expression of the growth-associated protein-43 (GAP-43) and synaptophysin (SYN). Furthermore, long-term potentiation (LTP) in hippocampal brain slices was decreased after PCT perfusion ex vivo. Our results indicated that PCT had neurotoxic effects on neuronal survival and synaptic plasticity, potentially leading to cognitive impairment after BM.

Malaria, caused by Plasmodium falciparum, presents significant challenges for treatment due to the parasite’s complex life cycle and increasing multi-drug resistance. Artemisinin-based combination therapies (ACTs) are the current standard treatment, resistance development necessitates the exploration of new therapeutic targets. Recent evidence suggests that targeting oxidative stress to arrest blood stage ring to schizont growth progression in Plasmodium could offer a novel approach to combat drug-resistant malaria. Phytomolecules have been recognized for their potential to modulate oxidative stress with artemisinin derivatives. In the present study, we aimed to evaluate the effectiveness of formononetin (FMT), a natural isoflavonoid, alone and in combination with artesunate (ART) against multidrug-resistant P. falciparum (K1) strain and to decipher the underlying mechanism of action. The study presents compelling evidence demonstrating the anti-plasmodial action of FMT alone (IC₅₀ value 212µM) and synergistic interaction (FICI 0.13) with ART at a 1:1 ratio against the K1 strain of P. falciparum. The combination treatment affected the progression of P. falciparum from the ring stage to the schizont and showed the effect at asexual erythrocytic stages. Moreover, the combination resulted in a notable increase in reactive oxygen species (ROS) levels, both independently and in combination with ART. In combination with ART, FMT effectively modulated the total glutathione (GSH) level. Moreover, FMT and ART demonstrated the ability to induce apoptosis-like death of parasites, as evidenced by the Lipid peroxidation (malondialdehyde-MDA) and DNA fragmentation (TUNEL) levels. These results indicate that FMT could potentially ameliorate the growth of multidrug-resistant malaria parasites, enhance the effects of ART, and be suitable for developing anti-plasmodial agents from a cheap and sustainable source.

Bovine viral diarrhea virus (BVDV) infection represents a significant economic challenge to the global cattle industry, leading to considerable losses in productivity and increased management costs. This underscores the urgent need for effective antiviral strategies to combat BVDV infection. In this study, we demonstrated that bovine lactoferrin (bLF), a multifunctional glycoprotein with known antimicrobial properties, exhibited potent inhibitory activity against BVDV infection. Importantly, the antiviral effect of bLF was not mediated by cytotoxicity towards host cells, indicating its safety for potential applications. Mechanistic investigations revealed that bLF did not interfere with viral RNA translation or replication, nor did it impair viral assembly or release. Instead, bLF effectively blocked BVDV infection during the early stages of the viral lifecycle, likely by competitively binding to cellular receptor molecules involved in viral entry. These findings identify bLF as a promising candidate for the development of antivirals targeting BVDV infection, offering a novel and effective approach to managing BVDV-associated diseases.

Rosmarinic acid (RA) is a valuable natural product for its significant antioxidative activity, which is mainly derived from plants or by chemical synthesis. With the development of biotechnology, the research on the production of RA by microbial cell factory has attracted more attention. In this study, we engineered Saccharomyces cerevisiae to produce RA by constructing a de novo RA synthesis pathway which utilized two cytochrome P450s from Salvia miltiorrhiza Bunge and Coleus scutellarioides (L.) Benth. Through reinforcing NAD(P)H regeneration by overexpression of zwf1 and integration of ARO4^K229L and ARO7^G141S into the genome, the engineered S. cerevisiae produced 4.92 mg/L of RA, 8.2-fold of the control, in shake flask fermentation. The titer of RA reached 11.3 mg/L by fed-batch fermentation in 5 L bioreactor. This study increased the production of RA by combination cofactor and pathway engineering, revealed the diversity of RA synthesis in S. cerevisiae, and also provided a reference for the synthesis and accumulation of other active components in yeast.

Folate, an essential water soluble vitamin B9 that cannot be synthesized naturally by the bodily function. Dietary sources or probiotic-folates are the two biological modes for acquiring the target vitamin which aids DNA synthesis and repair. Probiotics are known for their divergent health benefits and have garnered significant interest. Particularly in microbial strains that produce folate offers a promising way to enhance the level of folate. Notably, folate-producing probiotic strain includes Lactiplantibacillus, Lactococcus, Bifidobacterium, and Streptococcus. As an emerging source of health benefits, folate producing probiotics helps in improving the gut microbiota for overall well-being of human body. On the other side, chemically synthesized folic acid were not highly advantageous as they lacks absorption, conversion and excretion. Hence, usage of microbial-folate are safer as it can easily undergo absorption and reduces severe side effects. The present review mainly focus on folate one-carbon metabolism, its significance in human health, folate deficiency and malabsorption, adverse effects and folate synthesis from probiotic bacterial strains, and also toxicological impacts. In particular, the beneficiary role of these probiotic strains were found to be associated with therapeutic applications in several diseases such as autoimmune disorder, metabolic disorders, and cardiovascular diseases (CVDs), wound healing, drug delivery and cancer.

Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, poses a significant global health challenge, particularly in the resource-limited regions where it causes high mortality. Regardless in the progress of treatment strategies, the emergence of drug resistance and limited efficacy requires the search of novel therapy and therapeutic targets. MicroRNAs, the crucial post-transcriptional regulators of gene expression, play critical roles in host–pathogen interactions. Here, we screened the miRNAs dysregulated during Leishmania donovani infection through literature search. hsa-miR-330-5p, one of the miRNAs which through human KEGG 2021 and Human Cyc 2016 analysis was found to be involved in multiple pathways including sphingolipid signaling pathway. Sphingolipids are important class of lipids involved in different cellular processes and therefore are the targets of many pathogens including Leishmania. hsa-miR-330-5p was found downregulated after 24 h of Leishmania donovani infection in THP-1 derived human macrophages. Target prediction of sphingolipid biosynthetic genes through in silico prediction tools showed 3^/ UTR of serine palmitoyltransferase long chain base subunit 1 to be a target of hsa-miR-330-5p. The in silico target prediction of hsa-miR-330-5p was validated by cloning the 3^/ UTR target sequence of gene, transfecting and performing luciferase assay in HEK 293 T cell line. Transfection of mimic of hsa-miR-330-5p reduced the luciferase activity which validated the in silico target prediction. Further, mimic of hsa-miR-330-5p inhibited the expression of the target gene, serine palmitoyltransferase long chain base subunit 1 and augmented the expression of pro-inflammatory cytokines in L. donovani infected THP-1 derived macrophages. Mimic of hsa-miR-330-5p also led to a significant reduction in the intracellular parasite burden in both THP-1 derived as well as primary human macrophages. This study has not only identified the sphingolipid biosynthesis regulatory miRNA but will also help in the development of novel and effective treatment strategy against leishmaniasis in future.

A tellurite-reducing isolate (Te1) was recovered from a soil sample receiving industrial effluents from Ismailia Canal, Egypt. The isolate exhibited dark black colonies when grown on solid medium containing potassium tellurite, which indicated the reduction of tellurite to black tellurium. The isolate was identified using 16S rRNA gene sequencing and was submitted to GenBank as Phytobacter diazotrophicus strain Te1 (PP724698). The tellurite reduction percentage was 96.5% ± 0.354%. Moreover, energy-dispersive X-ray (EDX) analysis confirmed the presence of tellurium nanostructure, with a 3.7 keV absorption peak along with phosphorus, sulfur, and oxygen, revealing a complex biogenic nature. Fourier-transform infrared (FTIR) spectroscopy identified distinct absorption peaks within the 400–4000 cm⁻¹ range, corresponding to various vibrational modes of chemical bonds, including those of lipids, proteins, polysaccharides, and free radicals. X-ray diffraction (XRD) analysis highlighted the nanoscale crystalline structure of the material, with broad peaks confirming limited crystallite size and structural disorder, and revealed tellurium peaks on a hexagonal phase at 2-theta values of 27.36°, 38.19° and 40.20°. According to the results of the response optimizer and the subsequent validation experiments, complete reduction of tellurium was achieved at a medium pH of 6.8, incubation temperature of 33.5 °C, tellurite concentration of 1375 μM, and agitation speed of 110 rpm for 96 h. Black Te nanostructure was visible intracellularly and extracellularly upon examination using the transmission electron microscope. To the best of the authors’ knowledge, this is the first report of tellurite reduction by Phytobacter diazotrophicus.

Epigenetic regulator (ER) genes, crucial for fungal growth and development, remain largely unexplored in Ganoderma lucidum, a medicinal mushroom valued for its bioactive compounds. This study identified 81 ER genes in G. lucidum, distributed across 12 chromosomes and classified into six families: 3 chromatin remodelers, 4 DNA methyltransferases, 7 histone acetyltransferases, 22 histone deacetylases, 23 histone methyltransferases, and 22 histone demethyltransferases. Comparative and phylogenetic analyses with other species revealed conserved orthologs and species-specific clusters. Gene duplication analysis suggested whole-genome duplication expanded ER gene families, primarily histone demethyltransferases under purifying selection. Additionally, gene structure, motif, and domain analyses revealed family-specific intron/exon organization and conserved domains. Transcriptome profiling across four developmental stages (mycelium, primordia, young and mature fruiting body) revealed dynamic stage-specific expression patterns, suggesting their developmental significance. The result of qRT-PCR validated the expression patterns for 18 ER genes, laying foundation for future research exploring epigenetic regulation in fungal development and bioactive compound production.

The rapid progression of antimicrobial resistance, fueled by the excessive use of antibiotics, has become a major public health concern. Among the pathogens contributing to this crisis, Staphylococcus aureus stands out as a significant therapeutic challenge, especially with the rise of resistant strains like Methicillin-Resistant S. aureus (MRSA). In this context, antimicrobial peptides (AMPs) emerge as a promising alternative, thanks to their unique mechanisms of action. Exploring the genomes of species such as Staphylococcus hominis, known for producing AMPs effective against S. aureus, offers promising opportunities for discovering novel therapeutic agents. In this study, Average Nucleotide Identity (ANI) combined with phylogenetic analysis identified a potential emerging subspecies of Staphylococcus hominis. The core genome analysis led to the identification of a potential antimicrobial peptide. The peptide model simulated with the S. aureus membrane model in molecular dynamics revealed that it interacts primarily with the lipids head groups, leading to an overall rigidification of the bacterial membrane.