Search Results (553)

Background/Objectives: Acne vulgaris is a chronic inflammatory skin disorder characterized by sebaceous gland hyperactivity, follicular hyperkeratinization, proliferation of Cutibacterium acnes (C. acnes), and subsequent inflammation. The development of effective therapeutics necessitates reliable preclinical models that accurately replicate key pathological aspects of the human disease. Methods: In this study, we established an inflammatory acne model in Wistar rats via the intradermal injection of live C. acnes into the ear pinnae and thoroughly characterized its temporal dynamics of the induced inflammation. Utilizing this model, we evaluated the protective efficacy of a whole-cell inactivated C. acnes vaccine (HI-C. acnes) formulated with adjuvants WS03 or MA107b. Results: Inflammation peaked between days 1 and 3 post-infection, manifesting as pronounced erythema, ear swelling, increased ear thickness, elevated bacterial load, and significant upregulation of pro-inflammatory cytokines (IL-6, IL-1β, and MCP-1). Histopathological examination revealed extensive neutrophil infiltration and microabscess formation, while immunohistochemistry confirmed localized overexpression of TNF-α, IL-1β, and CXCL1 within the lesional tissue. Inflammatory manifestations gradually subsided by day 5 and were fully resolved by day 7, which coincided with complete bacteria clearance and normalization of pro-inflammatory cytokine levels. Vaccinated rats developed significantly higher C. acnes-specific IgG titers and, upon challenge, exhibited markedly reduced ear swelling, diminished bacterial burden, and suppressed expression of key inflammatory mediators compared to control groups, indicating that vaccine-induced protection is associated with humoral immunity. Conclusions: Collectively, our standardized and quantifiable rat ear inflammation model provides a robust platform for mechanistic investigations and preclinical assessment of novel anti-acne vaccines and therapeutic agents. Full article

Probiotics are live microorganisms that provide health benefits when administered in adequate amounts. Due to the increasing popularity of probiotic supplements, concerns have arisen regarding their quality, microbial composition, and safety. This study aimed to evaluate the quantitative and qualitative characteristics of the selected probiotics available on the Polish market, including both dietary supplements and foods for special medical purposes, and to compare the obtained results with the information provided on the product labels. Fifteen commercial probiotic products were analysed. Viable microorganism counts were determined using the traditional culture-based plate count method and by flow cytometry for selected products. Species identification was performed using MALDI-TOF MS and qPCR, whereas microbiological purity testing was conducted to confirm the absence of pathogenic bacteria. Significant differences were observed between the declared and experimentally determined numbers of viable microorganisms. Only a few products maintained bacterial counts consistent with label claims, while most contained considerably low viable cells. Flow cytometry revealed higher viable cell counts than plate counting, indicating the presence of viable but non-culturable bacteria. The declared species composition of the strains was mostly confirmed, although in several cases, undeclared probiotic microorganisms were identified. All tested products were free from pathogens. The study indicates significant discrepancies in the quality of probiotic supplements available on the Polish market. From a consumer perspective, these findings highlight the importance of verifying probiotic quality and suggest that not all commercial products may guarantee the full range of claimed health benefits. The implementation of standardised analytical procedures and enhanced quality control measures is therefore essential to ensure the product safety, strain authenticity, and reliability of health-related claims. Full article

Lipopolysaccharide (LPS) is widely used to model immune stress in weaned piglets, but it does not fully replicate the pathophysiological alterations induced by live bacterial infection. This study therefore established an oral Salmonella enterica (SE) challenge model and systematically compared its effects with those of LPS to evaluate its potential as a complementary immune stress paradigm. Forty piglets were assigned to five groups: control (saline), LPS (intraperitoneal, 100 μg/kg BW), and three SE groups receiving low-, middle-, or high-dose oral SE (1 × 10⁸ CFU/mL, 2 × 10⁸ CFU/mL, or 3 × 10⁸ CFU/mL in a 10 mL saline volume, respectively). Both LPS and SE significantly reduced average daily gain, while only SE challenge decreased colon length. A transient rectal temperature elevation occurred at 8 h in all challenged groups, persisting at 12 h in the LPS and high-dose SE groups. Serum cytokine analysis revealed that LPS induced early but transient interleukin-12 and tumor necrosis factor-α elevation at 8 h, followed by sustained suppression of interferon-γ, interleukin-6, and interleukin-8. In contrast, the middle-dose SE triggered robust increases in multiple pro-inflammatory cytokines at 24 h. Both challenges significantly reduced the CD4⁺/CD8⁺ T cell ratios in blood and lymphoid organs and decreased intestinal interleukin-10 levels. SE infection produced more severe intestinal pathology, including dose-dependent villus perforations, microvillus disorganization, and mitochondrial cristae vacuolization, beyond the villus shortening and goblet cell reduction observed in both groups. While both LPS and SE induced immune stress and intestinal injury, SE infection caused more severe and comprehensive pathophysiological alterations. Oral administration of 2 × 10⁹ CFU SE for 24 h established a physiologically relevant immune stress model that effectively mimics natural Salmonella infection in weaned piglets, providing a valuable tool for studying enteric diseases and evaluating interventions. Full article

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article

Background/Objectives: Discriminating bacterial from mammalian membranes remains a central challenge in antibiotic design. Bacterial membranes are enriched in phosphatidylethanolamine (PE), a lipid normally absent from the outer leaflet of mammalian cells, providing a signature for selective molecular engagement. We report a compact covalent ligand, 6-dimethylamino-4-ketohexanoic acid (DMAX), which targets PE via Schiff base formation, leveraging its tertiary amine to facilitate the reaction and strengthen ionic binding with the phosphate group. Methods: The reactivity of DMAX and PE was evaluated by computational simulations, and their interaction was examined by spectroscopic analyses (NMR and FT-IR) and an artificial membrane assay. The targeting ability of DMAX for live bacteria was determined by microscopy study, and its applicability to therapeutic system was tested in vitro under washed conditions that mimic rapid in vivo clearance. Results: Spectrometric analyses revealed the selective covalent interaction of DMAX and PE, consistent with the simulated results. Fluorescently labeled DMAX selectively binds PE-enriched model membranes and efficiently recognizes Gram-negative bacteria while sparing mammalian cells. Conjugation of DMAX to Gemifloxacin (Gem) significantly enhanced antibiotic efficacy by 10-fold compared with free Gem, even after rapid drug clearance, while maintaining safety in mammalian cells. Conclusions: These results identify DMAX as an efficient and versatile PE-targeting platform, enabling selective membrane anchoring to advance precision antibiotic strategies. Full article

In this study, we characterized the holin-like protein ORF70 from the cyanophage MaMV-DC, offering valuable insights into its role in phage-mediated host cell lysis. ORF70 shares key features with class III holins, such as a hydrophobic transmembrane domain and membrane-associated localization, which are crucial for its bacteriolytic activity. Subcellular localization studies suggested its association with the membrane, supporting its classification as a holin-like protein. Overexpression of ORF70 in E. coli resulted in significant growth inhibition, increased β-galactosidase leakage, and visual confirmation of cell death through live/dead staining. Additionally, ORF70’s sensitivity to the energy toxin 2,4-dinitrophenol (DNP) further indicated its holin-like activity by promoting membrane depolarization. Transmission electron microscopy and Gram staining revealed characteristic morphological changes in E. coli cells, including membrane disruption, consistent with damage caused by holins. These results suggest that ORF70 acts as a holin-like protein that disrupts the host membrane, leading to bacterial cell death. Our study provides evidence supporting the holin-like activity of ORF70 from cyanophage MaMV-DC. This research significantly enhances our understanding of phage-host interactions and opens new avenues for developing phage-based therapies, offering promising alternatives to traditional antibiotics amidst the growing challenge of antibiotic resistance. Full article

Silver nanoparticles (AgNPs) are widely used as antibacterial agents either as colloidal solutions or deposited on surfaces. However, the high concentration of AgNPs can lead to cytotoxicity, posing a hazard to healthy cells and tissues. Achieving a balance between antibacterial efficacy and cytocompatibility is crucial for biomedical applications. Polymeric coatings, especially those made from polydimethylsiloxane (PDMS) like Sylgard 184, are popular in biomedical applications due to their user-friendliness. We have developed a cost-effective method to reduce silver ions using the Si-H silane functions of PDMS in situ. Tetrahydrofuran (THF) acts as a solvent, inducing a swelling effect in PDMS, allowing silver ions from silver tetrafluoroborate (AgBF₄) dissolved in THF to diffuse into the polymer and undergo reduction. This process results in PDMS functionalized with well-distributed 10 nm silver AgNPs. The resulting metal–polymer nanocomposites (MPNs) exhibit yellow shades and, based on qualitative Live/Dead staining observations, show no apparent cytotoxicity on human gingival fibroblasts. In addition, SEM analyses indicate a qualitative reduction in E. coli adhesion, suggesting an antibacterial anti-adhesive potential against this bacterial strain. Further studies should investigate the release profile of AgNPs in these composites, which could guide the development of new biocompatible coatings for phototherapy devices and enhance their long-term clinical performance. Full article

Human infections caused by pathogenic bacteria remain a major global health concern. Among them, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi are particularly prevalent and associated with significant morbidity and mortality. While antibiotics have long been the cornerstone of bacterial infection treatment, the widespread and often inappropriate use of these drugs has led to the emergence of multidrug-resistant (MDR) strains. This escalating resistance crisis underscores the urgent need for alternative therapeutic strategies. Amid the escalating global antimicrobial-resistance crisis, a genome-wide screen of 1800 Saccharomyces cerevisiae knockouts identified a TAD1-deficient mutant whose cell-free supernatant (CFS) rapidly eradicates multidrug-resistant E. coli, S. aureus, K. pneumoniae, and S. typhi in vitro. CFS disrupts pathogenic biofilms, downregulates biofilm-associated genes, and exerts bactericidal activity by triggering intracellular reactive oxygen species (ROS) accumulation and compromising envelope integrity. Probiotic profiling revealed robust tolerance to an acidic pH and physiological bile, high auto-aggregation, and efficient co-aggregation with target pathogens. In both Galleria mellonella and murine infectious models, administration of CFS or live yeast significantly increased survival, attenuated intestinal histopathology, and reduced inflammatory infiltration. These data establish the TAD1-knockout strain and its secreted metabolites as dual-function antimicrobial-probiotic entities, offering a sustainable therapeutic alternative to conventional antibiotics against multidrug-resistant bacterial infections. Full article

Microcystis aeruginosa formed in natural water bodies grow in aggregate particles, while Microcystis aeruginosa commonly used in scientific research grow in a single-celled discrete state during cultivation. To elucidate the factors and mechanisms of Microcystis aeruginosa entering the “cell-aggregate” survival state in the natural environment, we focused on studying the influence of biological factors in their living environment (coexisting bacteria) on the aggregation behavior and growth characteristics of Microcystis aeruginosa. The bacterial strain A20, which can promote the aggregative behavior of Microcystis aeruginosa, was isolated from the water of Taihu Lake, where a cyanobacterial bloom broke out. A20 was identified as Priestia megaterium. Results showed that A20 could significantly drive Microcystis aeruginosa to form sac-like aggregate structures and promote the increase of aggregate particle size from 3–7 μm to 180 μm. The coexistence of bacteria and algae exhibited a dynamic stage adaptation strategy, with A20 promoting the transition of Microcystis aeruginosa from “high-chlorophyll, low-photochemical efficiency growth and proliferation” to “stable survival and maintenance of chlorophyll and photochemical efficiency in fluctuating changes” adaptation strategies. The coexistence of bacteria and algae significantly intensified the release of humic acid-like, fulvic acid-like, and protein-like substances from Microcystis aeruginosa, with the most significant increase in small-molecule fulvic acid-like substances. This is probably related to the endogenous metabolic stress response of Microcystis aeruginosa during A20 invasion, as well as the utilization and transformation of autotrophic Microcystis aeruginosa metabolites by heterotrophic bacteria A20. This study contributes to the study of microbial interactions underlying bloom outbreaks and can be useful for developing community-targeted algal control technologies. Full article

Plant cell wall polysaccharides (PCWPs) serve as an abundant but recalcitrant carbon source for many microbes living in the gut of humans and animals. An adhesion to PCWPs is common in gut bacteria and can even be observed in the lactobacilli, which are supposed to promote the growth competence of these non-PCWP degraders because of the facilitated acquisition of newly released oligosaccharides. Nevertheless, the binding of molecules of lactobacilli to PCWPs and the underlying mechanisms remain largely unknown. By analyzing the transcriptome of Lactobacillus brevis grown in xylan supplemented with a xylanase, a gene was identified to encode a putative S-layer PCWP-binding protein (Lb1145). Lb1145 was predicted to have four domains, among which domains 1 and 2 were responsible for binding PCWPs. The binding was nonspecific, since structurally distinct PCWPs, e.g., cellulose, xylan, mannan, and chitin, and even lignin, were all bound by Lb1145. Both of the two N-terminal domains have a high pI, and we demonstrated that a non-enzymatic glycosylation-like process plays an important role in binding. Compared with another L. brevis surface protein, i.e., the WxL protein Lb630, Lb1145 displayed a binding preference for the phloem sieve tube in the wheat stem section. Moreover, Lb1145 could bind ten strains within the Lactobacillus, Enterococcus, Pediococcus, and Bacillus genera among the seventeen selected gut bacterial species. An analysis of the reported S-layer proteins from the Gram-positive bacteria (lactobacilli and bifidobacteria) and outer membrane proteins from the Gram-negative (Bacteroides fragilis and Prevotella intermedia) indicated that bacterial cell surface proteins with high pI values are not rare. The high pI-based and non-enzymatic glycosylation-like process-mediated binding represents a new paradigm and may be popular in gut bacterial surface proteins binding to PCWPs, with important physiological implications in growth competition in the gut microbiota. Full article

Mastitis is one of the major diseases affecting dairy cattle worldwide. Antibiotic therapy remains the most widely used treatment. However, its effectiveness has been compromised due to the selection of antibiotic-resistant and biofilm-producing pathogenic bacteria. This promotes the search for alternatives that increase the antibacterial and antibiofilm efficacy of antibiotics such ceftiofur (CFT). Nisin (N) and chitosan (CH) may possess these properties. The aim of this study was to evaluate whether N + CFT and CH + CFT combinations enhance the antibacterial activity of the antibiotic on Staphylococcus aureus associated with bovine mastitis, as well as its antibiofilm effect. Two clinical isolates of S. aureus (AMC-43 and AMC-48) and the reference strain ATCC 27543 resistant to CFT were used. Through the microdilution method in 96-well microplates, the combination of sub-inhibitory concentrations of N (320 µg/mL) and CH (400 µg/mL) with CFT (1, 2, 4, and 8 µg/mL) significantly reduced bacterial growth; however, the CH + CFT mixtures were the most efficient. The crystal violet staining method and live cell plating showed antibiofilm activity in biofilm synthesis and in the reduction in living bacterial cells located inside this preformed structure. These results highlight N and CH as potential agents for the prevention or control of bovine mastitis. Full article

The issue of antibiotic resistance is becoming increasingly severe, urgently requiring the development of new antibacterial strategies. Photodynamic therapy (PDT) has gradually emerged as a promising alternative due to its spatiotemporal controllability, low risk of drug resistance, and broad-spectrum antibacterial properties. However, most existing photosensitizers (PSs) are hydrophobic, which limits their application efficiency in PDT. To address this problem, we designed and synthesized a water-soluble perylene diimide derivative (PDICN-CBn) as a photosensitizer. By introducing quaternary ammonium salt groups, its water solubility was improved, and antibacterial activity was enhanced. Subsequently, PDICN-CBn was assembled into silk fibroin/polylactic acid (SF/PLA) nanofibrous membranes via electrospinning technology, successfully constructing a visible-light-responsive ternary composite nanofibrous membrane (SF/PLA@PDICN-CBn). Using various characterization methods such as nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM), the microstructure, chemical composition, and structural characteristics of the nanofibrous membranes were systematically analyzed, verifying the successful synthesis of the photosensitizer and its assembly into the nanofibrous membranes. In the reactive oxygen species (ROS) experiment, electron spin resonance (ESR) spectra showed that PDICN-CBn efficiently generated singlet oxygen (¹O₂), superoxide anion (·O₂⁻), and hydroxyl radical (·OH) under visible light irradiation, confirming its ability to produce different types of ROS through both type I and type II photodynamic reactions. In the antibacterial experiments, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA) were selected for a series of tests, including plate-counting antibacterial assays, bacterial live/dead staining, and SEM observation of morphology. The results showed that 8 μg/mL of PDICN-CBn effectively destroyed the bacterial cell membrane structure and killed bacteria (bactericidal rate > 95%) after 2 h of visible light irradiation. This work successfully developed a novel visible-light-responsive SF/PLA@PDICN-CBn nanofibrous membrane with a dual antibacterial system combining photodynamic and electrostatic adsorption antibacterial properties, providing new ideas and methods for the design and development of photodynamic antibacterial materials. The prepared nanofibrous membrane has potential application values in fields such as wound dressings and medical protective materials and is expected to provide strong support for solving clinical infection problems. Full article

Because of their technical qualities, such as resistance to fading and to high temperatures, mineral pigments are still widely used. Among mineral pigments, iron oxide pigments represent a widely used class, because of their diversity of shades (from yellow to red to brown to black) and low toxicity compared to heavy metals-based pigments. However, low toxicity does not mean the absence of adverse effects. We thus investigated the biological effects of two different subtypes of Pigment Red 101, i.e., hematite, produced by two different processes, namely a wet precipitation process and a calcination process. Macrophages were chosen as a target cell type because they represent the main scavenger cell type that is in charge of handling particulate materials in the body. During this comparison, we realized that the calcined pigment was contaminated from the start by bacterial endotoxins, which induced intense inflammatory responses and biased the comparison. After depyrogenation, the calcined pigment proved to dissolve to a higher extent in macrophages, but to show less intense adverse effects (e.g., alteration of the mitochondrial transmembrane potential, oxidative stress and inflammatory responses) than the precipitated pigment in a recovery exposure mode, allowing us to investigate delayed effects of the pigments. Thus, despite their identical pigment number, pigments differing in their structure and in their synthesis induce different responses from living cells, even if administrated in equivalent amounts. This should be taken into account for some applications, such as tattooing. Moreover, endotoxin contamination should also be checked to increase workers’ and users’ safety. Full article

Although traditionally sidelined by live probiotic effects, Lactobacilli-derived Microbe-Associated Molecular Patterns (MAMPs) are emerging as potent modulators of innate and adaptive immune responses, capable of acting independently of bacterial viability. However, the underlying mechanisms remain incompletely understood. These MAMPs, such as peptidoglycan (PGN), lipoteichoic acid (LTA), and exopolysaccharides (EPSs), interact with pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), initiating immune-signaling cascades that regulate cytokine production and inflammation. Lactobacilli-derived MAMPs exhibit dual immunomodulatory effects: they can enhance pro-inflammatory responses, e.g., interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) under inflammatory contexts, while enhancing regulatory pathways via IL-10 and regulatory T-cell (T_regs) induction in anti-inflammatory settings. Importantly, these immunomodulatory properties persist in the absence of bacterial viability, making MAMPs promising candidates for postbiotic therapies. This opens new avenues for MAMP-based strategies to target inflammation, overcoming the risks associated with live bacterial administration. This review examines the therapeutic relevance of non-viable MAMPs, particularly in inflammatory diseases where they have demonstrated benefits in reducing tissue damage, enhancing gut barrier function, and alleviating disease symptoms. Additionally, we discuss regulatory and translational challenges hindering their clinical implementation, highlighting the need for standardized characterization, a clear safety framework, and strain-specific profiling. Given their ability to fine-tune immune responses, MAMPs represent an emerging strategy for innovative treatments aimed at restoring immune balance and reinforcing host–microbe interactions. Full article

Methodological fusion of materials chemistry, which enables us to create materials, with nanotechnology, which enables us to control nanostructures, could enable us to create advanced functional materials with well controlled nanostructures. Positioned as a post-nanotechnology concept, nanoarchitectonics will enable this purpose. This review paper highlights the broad scope of applications of the new concept of nanoarchitectonics, selecting and discussing recent papers that contain the term ‘nanoarchitectonics’ in their titles. Topics include controls of dopant atoms in solid electrolytes, transforming the framework of carbon materials, single-atom catalysts, nanorobots and microrobots, functional nanoparticles, nanotubular materials, 2D-organic nanosheets and MXene nanosheets, nanosheet assemblies, nitrogen-doped carbon, nanoporous and mesoporous materials, nanozymes, polymeric materials, covalent organic frameworks, vesicle structures from synthetic polymers, chirality- and topology-controlled structures, chiral helices, Langmuir monolayers, LB films, LbL assembly, nanocellulose, DNA, peptides bacterial cell components, biomimetic nanoparticles, lipid membranes of protocells, organization of living cells, and the encapsulation of living cells with exogenous substances. Not limited to these examples selected in this review article, the concept of nanoarchitectonics is applicable to diverse materials systems. Nanoarchitectonics represents a conceptual framework for creating materials at all levels and can be likened to a method for everything in materials science. Developing technology that can universally create materials with unexpected functions could represent the final frontier of materials science. Nanoarchitectonics will play a significant part in achieving this final frontier in materials science. Full article