Search Results (1,054)

The cell envelope of Gram-positive bacteria is a primary target of host immune defenses and antibiotics, and its stability is influenced by environmental factors, including the availability of the divalent cations Mg²⁺ and Ca²⁺. Alanine also plays a critical role in cell envelope integrity, contributing to peptidoglycan cross-linking, D-alanine modification of teichoic acids, and protein synthesis. However, how these factors functionally interact to maintain envelope stability in S. aureus remains unclear. Here, we demonstrate that growth of S. aureus under Mg²⁺-limited and Ca²⁺-limited conditions requires increased alanine uptake mediated by the transporter AapA. Loss of AapA results in increased cell lysis and impaired growth under cation-limited conditions, and removing alanine from the growth medium phenocopies these aapA mutant defects. Alanine limitation increases susceptibility to the detergent Triton X-100 and the membrane-targeting antibiotic daptomycin, consistent with defects in envelope stability. Furthermore, aapA function contributes to bacterial fitness in insect and murine infection models. Together, these findings indicate that Mg²⁺, Ca²⁺, and alanine play overlapping roles in stabilizing the S. aureus cell envelope, pointing to AapA as a target that may leveraged to enhance antimicrobial efficacy. Full article

Background/Objectives: Titanium alloy Ti₆Al₄V remains the gold standard in dental implantology due to its excellent mechanical properties, corrosion resistance, and biocompatibility. However, implant-associated infections and insufficient osseointegration continue to represent major clinical challenges, mainly related to bacterial biofilm formation and suboptimal surface–tissue interactions. Biofilm formation refers to the adhesion, accumulation, and growth of microbial communities embedded within a self-produced extracellular polymeric matrix on implant surfaces, which contributes to bacterial persistence and resistance to host defense mechanisms. This review aims to critically evaluate recent advances in multifunctional bioceramic coatings for dental implants, with a particular focus on zirconia (ZrO₂)-based systems and their antibacterial mechanisms. Methods: A structured literature analysis was conducted using major scientific databases including PubMed, Scopus, and Web of Science, focusing mainly on studies published between 2015 and 2025 related to CaP, Ag, and ZrO₂-based coatings for dental implants. The review examines their physicochemical properties, antibacterial strategies, ion release behavior, and biological responses, including osteogenic activity and biofilm inhibition. Particular attention is given to hybrid systems integrating multiple functional phases. Results: CaP coatings exhibit excellent osteoconductivity and promote early osseointegration but show limited intrinsic antibacterial activity. Ag-based coatings provide strong broad-spectrum antimicrobial effects through controlled Ag⁺ ion release, although concerns regarding cytotoxicity and dose-dependent responses remain. ZrO₂ coatings significantly enhance corrosion resistance and surface stability, while their antibacterial performance can be improved through nanostructuring, laser surface modification, and ionic doping. Hybrid Ag–CaP–ZrO₂ coatings demonstrate improved antibacterial activity, enhanced corrosion resistance, and better regulation of ion release kinetics and osteogenic response compared with single-component coating systems. Conclusions: Multifunctional bioceramic coatings represent a promising strategy for improving the performance of dental implants and addressing the dual challenge of infection control and tissue integration. However, challenges remain regarding long-term stability, controlled ion release, and limited clinical validation. Future research should focus on the development of smart, stimuli-responsive coatings and standardized evaluation protocols to facilitate clinical translation. Full article

Gingivitis, periodontitis, and stomatitis are common oral inflammatory disease affecting a large proportion of the global population. Increasing attention has recently been given to the development of health functional materials aimed at maintaining oral health and preventing microbial-associated oral disease. This study evaluated the efficacy of the lipoteichoic acid (LTA) fraction derived from the probiotic Lactiplantibacillus plantarum K8 (pLF) in preventing oral inflammation and microbial infection using the oral epithelial cell line YD-38. The results confirmed that pLF enhances the expression of interleukin-1 receptor-associated kinase M (IRAK-M), a negative regulator of Toll-like receptor (TLR) signaling, and inhibits the expression of pro-inflammatory cytokines, including C-C motif ligand 2 (CCL2), interleukin-6 (IL-6), and interleukin-8 (IL-8), in YD-38 cells stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Furthermore, it was demonstrated that pLF induces IRAK-M expression in a TLR2-involved manner and inhibits nuclear factor-kappa B (NF-κB) signaling, thereby reducing the expression of pro-inflammatory cytokines. pLF also exhibits oral antimicrobial efficacy by increasing the expression of the antimicrobial peptide human β-defensin 1 (hBD1) and human β-defensin 2 (hBD2) in a TLR2-involved manner and effectively inhibiting the growth of Porphyromonas gingivalis and Staphylococcus aureus in the epithelial cell associated system. Therefore, the LTA fraction derived from L. plantarum K8 represents a promising postbiotic candidate for the regulation of oral immune and microbial responses. Full article

Background/Objectives: Antimicrobial resistance (AMR) in Escherichia coli is a growing public health concern, particularly in regions affected by environmental contamination and poor wastewater management. Data on locally isolated E. coli-targeting phages in Lebanon remain limited. This study aimed to isolate, characterize, and evaluate two lytic bacteriophages against AMR E. coli. Methods: Two phages, EPIMAM01 (gb:PQ493298) and EPIMRB01 (gb:PQ657784), were isolated from untreated sewage in Beirut using E. coli ATCC 25922. Characterization included double-layer agar assays, one-step growth analysis, and stability testing across temperature and pH ranges. Bacteriolytic activity was assessed in planktonic cultures and preformed biofilms. Host range and efficiency of plating (EOP) were evaluated using clinical isolates. Whole-genome sequencing and comparative analyses were performed. Results: Both phages produced clear plaques and showed a latent period of ~40 min. EPIMAM01 had a higher estimated burst size (140 PFU/infected cell) than EPIMRB01 (75 PFU/infected cell). Both phages remained stable between 4–50 °C and within a pH range of 5–10 but showed marked loss of activity at temperatures ≥60 °C and pH ≤3 or ≥12. EPIMAM01 effectively inhibited planktonic growth of E. coli ATCC 25922, whereas EPIMRB01 showed stronger biofilm-disrupting activity against preformed E. coli biofilms. Both phages lysed several of the 17 tested clinical E. coli isolates. Comparative analyses of gene presence/absence patterns, bacterial defense systems, and adsorption phenotypes among the tested E. coli strains identified mlaA, ydcQ, and ompD-2 as candidate adsorption-associated genes and suggested CRISPR systems may reduce susceptibility. Genomic analysis classified both phages as T4-like phages lacking lysogeny, virulence, or AMR genes. Conclusions: EPIMAM01 and EPIMRB01 are lytic phages with complementary antimicrobial properties, supporting their potential for further development as AMR control agents. Full article

Background/Objectives: Antimicrobial resistance (AMR) represents one of the most pressing global public health challenges, with inappropriate antibiotic prescribing being a major contributor. In Hungary, general practitioners (GPs) account for over 70% of all antibiotic prescriptions, yet limited research has examined the complex relationship between patient expectations and physician prescribing behavior. This study explores general practitioners’ antibiotic prescribing practices and their perceptions of patient expectations. Methods: A cross-sectional study was conducted among 181 GPs in Hungary from March 2024 to April 2025. The sample is representative of the northeastern region of Hungary. Participants completed anonymous paper-based questionnaires assessing their self-reported professional knowledge, perceived patient expectations, prescribing behavior, and antibiotic stewardship practices. Results: Most respondents recognized antimicrobial resistance as a significant public health issue (81.7%, n = 147); however, only 52.2% (n = 94) felt capable of effectively taking action against it. While 80.6% (n = 145) reported that patients expect antibiotic prescriptions and 71.1% (n = 128) experienced conflicts over prescribing refusals at least once within the previous six months, 87.2% (n = 157) stated they do not yield to patient pressure. Concerning patterns emerged: 56.1% (n = 101) reported completing patient-initiated antibiotic courses, 36.1% (n = 65) admitted to “just-in-case” prescribing at least once within the past six months, and 38.9% (n = 70) encountered self-medication despite regulations restricting antibiotics to prescription-only use. Only 17.8% (n = 32) regularly monitored their antibiotic prescribing indicators. Physicians with multiple specialty qualifications reported less frequent patient education and more conflicts (p = 0.010). Conclusions: General practitioners demonstrate resilience despite substantial patient pressure; however, self-medication and defensive prescribing practices reveal important gaps in antimicrobial stewardship. Targeted, multifaceted interventions addressing both prescriber behavior and systemic vulnerabilities are needed to strengthen stewardship efforts. Full article

Honeybee (Apis mellifera) health is governed by the integrated action of detoxification, immunity, and microbiota within complex environmental contexts. The coordinated detoxification system (DETOXome), primarily active in the midgut, fat body, and Malpighian tubules, includes cytochrome P450s, glutathione S transferases, carboxylesterases, and ABC transporters, and functions in concert with innate immune pathways such as Toll, Imd, Jak/STAT, JNK, antimicrobial peptides, and RNA interference. Cellular maintenance mechanisms, including heat shock proteins, proteostasis, and antioxidant defenses, support these systems under chemical, thermal, and pathogen-induced stress. Multi-stressor exposures encompassing pesticides, pathogens, nutritional limitations, and climate variations interact to affect physiological resilience, behavior, and colony function. This review synthesizes molecular, organ-specific, and colony-level evidence to provide a mechanistic framework connecting environmental stressors to detoxification and immune responses. Predictive markers derived from transcriptomic, proteomic, and microbiome analyses offer early detection of sublethal stress, while genomic and selective breeding strategies hold the potential to enhance honeybee resilience. By integrating stress pathways across biological scales, this review advances a unified model of honeybee health that moves beyond descriptive lists to highlight cross-system interactions driving colony survival. Full article

Ethanol is a pervasive chemical stressor in fermentative environments and represents a major ecological challenge for Drosophila melanogaster, a species that naturally inhabits decaying fruits. Although ethanol tolerance has traditionally been attributed to detoxification and antioxidant pathways, accumulating evidence indicates that immune-related genes, particularly those encoding immune deficiency (IMD) pathway-associated antimicrobial peptides (IMD-AMPs), contribute importantly to chemical stress adaptation. Previous studies have demonstrated that IMD-AMP induction is required for ethanol tolerance; however, whether elevated IMD-AMP expression alone is sufficient to enhance tolerance has remained unresolved. In this study, we investigated the functional significance of IMD-AMP upregulation in ethanol tolerance using dietary propolis as an experimental immune-modulating agent. D. melanogaster were reared throughout their life cycle on propolis-supplemented diets and subsequently exposed to ethanol. Propolis-fed flies exhibited significantly enhanced survival under ethanol stress compared with control flies. Notably, this increased tolerance was not accompanied by upregulation of classical ethanol metabolism genes or broad induction of antioxidant-related genes. Instead, propolis feeding increased baseline and early-stage expression of IMD-AMP genes, including Diptericin A (DptA), Diptericin B (DptB), Attacin (AttC), and Metchnikowin (Mtk) before and during ethanol exposure. These findings suggest IMD-AMP upregulation is positively associated with enhanced ethanol tolerance in D. melanogaster. Our results establish a proactive role for immune-related pathways in chemical stress resistance and extend the functional scope of AMPs beyond pathogen defense. This study identifies IMD-AMPs as key effectors linking immune activation to physiological adaptation under ethanol-induced chemical stress. Full article

Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized components with potent antimicrobial properties as part of a defense mechanism against prey-borne microorganisms. This study evaluated the inhibitory potential of Micrurus venoms against pathogens of agricultural interest and developed bioactive gelatin-based films incorporated with purified L-amino acid oxidases (LAAOs) as a novel biocontrol strategy. Venoms from M. ancoralis, M. mipartitus, and M. dumerilii exhibited significant growth inhibition against Xanthomonas and Fusarium strains. The primary active component was identified as LAAO through biological activity and mass spectrometry. Biofilms were formulated by incorporating M. ancoralis venom and its purified LAAO into a gelatin matrix. Physicochemical and microbiological characterization, alongside in situ assays on strawberries, demonstrated that the functionalized biofilms retained potent antimicrobial activity. Furthermore, LAAO incorporation did not significantly alter the physicochemical properties of the fruit but effectively extended shelf life by reducing weight loss and maintaining sensory appearance. These findings highlight the biotechnological potential of elapid venom components in the development of alternatives for phytopathogen control and active food packaging. Full article

Next-generation vaccines are being developed to elicit durable and cross-protective immune responses against diverse pathogens, particularly those targeting the respiratory and enteric systems. By strategically engaging T cell-centric antigen design, mucosal immune engagement, and induction of trained innate immunity, these innovative platforms are expected to reshape the paradigm of immunoprophylaxis and to offer promising avenues for enhanced protection against complex infectious diseases. Conventional antibody-based vaccines, though effective against many infections, often lack the capacity to induce durable or cross-protective immunity at mucosal surfaces. Advances in antigen design, delivery platforms, and adjuvant technologies now facilitate precise activation of tissue-resident memory T cells and enhancement of mucosal secretory IgA responses, thereby achieving sterilizing immunity at barrier surfaces while reinforcing systemic immune protection. Advanced delivery platforms, including lipid nanoparticles, viral vectors, and nano or liposomal carriers, further refine antigen presentation, enhancing stability, targeting, and overall immunogenicity. Concurrently, progress in understanding trained innate immunity highlights opportunities to induce broad, non-antigen-specific protection through epigenetic and metabolic reprogramming of innate cells. The integration of these adaptive and innate mechanisms may enhance early pathogen control, limits transmission, and strengthens defense against variant and antimicrobial-resistant pathogens across diverse populations. However, translating these immunological insights into safe, scalable, and globally accessible vaccines remains a major challenge. This review explores the emerging conceptual framework of next-generation vaccines that demonstrate partial integration of these axes in preclinical models, though human translation and functional synergy require Phase II validation. It highlights progress toward next-generation vaccines leveraging integrated adaptive and innate immune reprogramming for superior protection against respiratory and enteric pathogens. Full article

Volatile organic compounds (VOCs) have garnered substantial research interest in recent years due to their biodegradability, low toxicity, and potent antimicrobial properties against various plant pathogens. As a typical herbivore-induced plant volatile (HIPV) elicited by Nilaparvata lugens (Brown planthopper, BPH), (E)-2-hexenal has been identified as a promising natural antimicrobial agent. In this study, we investigated the protective potential of (E)-2-hexenal against Rhizoctonia solani (R. solani) in rice, focusing on both its direct antifungal activity and host-mediated defense mechanisms. In vitro antifungal assays demonstrated that treatment with 100 μL/mL (E)-2-hexenal resulted in a 91.07% inhibition of R. solani mycelial growth after 48 h. Scanning electron microscopy (SEM) observation and chitinase activity analysis revealed that (E)-2-hexenal suppressed fungal growth by disrupting the structural integrity of the pathogen cell wall. Furthermore, 100 μL/mL (E)-2-hexenal effectively conferred protection to detached rice leaves. Whole-plant inoculation assays confirmed that (E)-2-hexenal pretreatment significantly alleviated disease symptoms and triggered systemic resistance in rice plants. Physiological and biochemical analyses showed that (E)-2-hexenal treatment enhanced the activities of defense-related enzymes, elevated hydrogen peroxide (H₂O₂) levels, and promoted the accumulation of defensive metabolites in rice leaves. HPLC-MS quantification further revealed significant increases in the endogenous levels of jasmonic acid (JA) and salicylic acid (SA). Transcriptomic KEGG pathway enrichment analysis indicated that differentially expressed genes (DEGs) were mainly involved in alpha-linolenic acid metabolism, diterpenoid biosynthesis, phenylpropanoid biosynthesis, plant–pathogen interaction, and plant hormone signal transduction. Collectively, these results suggest that (E)-2-hexenal enhances rice resistance to sheath blight disease via a dual-action mechanism: direct inhibition of fungal development and activation of host immune responses. Our findings highlight the potential application of (E)-2-hexenal and other VOCs in developing eco-friendly strategies for sustainable rice disease management. Full article

Coffee is among the most widely consumed beverages globally being cultivated in nearly 80 countries. Its processing generates large quantities of by-products, including mucilage, pulp/husks, silverskin, parchment, and spent coffee grounds. Although traditionally treated as waste, these residues are increasingly recognized as valuable resources rich in bioactive compounds exhibiting antioxidant, antimicrobial, and health-promoting properties. This review explores the antimicrobial potential of coffee by-products, with particular emphasis on their chemical composition and mechanisms of action. Compounds such as caffeine, chlorogenic acids, polyphenols, and melanoidins have demonstrated inhibitory effects against a broad spectrum of bacteria, including both Gram-positive and Gram-negative bacteria. Many of these compounds, which originate from plant’s defensive system or result from Maillard reactions, are known to disrupt microbial membranes, inhibit DNA repair, and interfere with pathogen metabolism. However, the available literature on their antimicrobial effectiveness remains limited. In the context of the rising worldwide concern over antimicrobial resistance, coffee by-products represent a sustainable and promising source of novel antimicrobial agents. Their valorization may support advances in food preservation, pharmaceutical innovation, and waste management practices, contributing to the implementation of a circular economy framework in the coffee industry while promoting environmental, economic, and social sustainability. Full article

Interleukin-17A (IL-17A) is a proinflammatory cytokine that plays a pivotal role in immune responses and tissue homeostasis. Its expression is strictly regulated by transcription factors including RORγt, and it is mainly produced by Th17 cells, γδ T cells, and innate lymphoid cells. IL-17A signals through a heterodimeric receptor complex consisting of IL-17RA and IL-17RC, activating NF-κB, MAPK, and C/EBP pathways via the adaptor protein Act1. IL-17 signaling is counterbalanced by negative regulators including A20 and Regnase-1. Beyond its classical roles in antimicrobial defense and autoimmune inflammation, recent studies have highlighted its functions in the central nervous system, with associations to multiple sclerosis, autism spectrum disorder, and Alzheimer’s disease. The development of IL-17A inhibitors, including the dual IL-17A/F antagonist bimekizumab, has advanced markedly, with demonstrated efficacy in immune-mediated diseases such as psoriasis and psoriatic arthritis. This review provides a comprehensive overview of current knowledge of IL-17A, from its molecular characteristics to clinical applications. Full article

Far-UVC 222 nm is a promising adjunctive disinfection technology for occupied healthcare environments, though antimicrobial efficacy varies significantly across pathogen types due to fundamental differences in microbial biology. This review synthesizes evidence on microbiological determinants of far-UVC resistance, examining cell envelope structure, biofilm formation, DNA repair capacity, and antioxidant defenses. A clear resistance hierarchy emerges. Enveloped viruses lacking enzymatic repair systems are highly vulnerable, requiring fluences below 3 mJ/cm². Gram-negative bacteria are readily inactivated through membrane disruption and reactive oxygen species accumulation. Gram-positive bacteria demonstrate higher resistance via thick peptidoglycan barriers, DNA repair mechanisms, and redundant antioxidant systems. Biofilm-embedded cells show 10–1000-fold increased tolerance due to protective extracellular matrices, stress-response gene upregulation, and microenvironmental heterogeneity. Clostridioides difficile spores exhibit extreme resistance through multilaminar protective coats and metabolic dormancy, requiring impractical doses exceeding 1000 mJ/cm². Field studies in real-world polymicrobial biofilm communities demonstrate substantially lower efficacy than laboratory predictions, typically achieving only 55–81% bioburden reductions. Understanding these pathogen-specific resistance mechanisms is essential for the rational deployment of far-UVC as an adjunctive infection prevention intervention in healthcare settings. Full article

Insects represent powerful experimental systems for investigating host–microorganism interactions, providing valuable insights into bacterial pathogenicity, immune regulation, symbiosis, and antimicrobial discovery. This review examines the complex relationships between insects and bacteria, focusing on the mechanisms that control infection, immune activation, and microbial adaptation. Particular attention is given to the routes of pathogen entry and to the conserved innate immune pathways that coordinate host defenses, including the Toll, Imd, Duox, and Jak/Stat signaling cascades. The review illustrates how bacterial pathogens exploit toxins, immune evasion strategies, and metabolic adaptation to overcome host defenses, while insects rely on tightly regulated cellular and humoral responses, antimicrobial peptides, melanization, and microbiota-mediated homeostasis. Interactions between pathogenic and commensal bacteria in the insect gut are discussed in the context of immune tolerance, dysbiosis, and ecological adaptation. The dual role of bacterial virulence factors in both pathogenesis and symbiosis is highlighted through examples involving entomopathogenic bacteria such as Photorhabdus spp., Xenorhabdus spp., and Bacillus thuringiensis. In addition, the review summarizes the use of insect models, including Drosophila melanogaster, Galleria mellonella, Bombyx mori, and Apis mellifera, in experimental infections aimed at studying virulence mechanisms, host immune responses, and antimicrobial efficacy. Finally, multi-omic approaches, including transcriptomics, metabolomics, epigenomics, and single-cell technologies are discussed as transformative tools for dissecting host–microbe interactions at molecular and systems levels. Overall, insect–bacteria interactions emerge as dynamic and evolutionarily shaped systems in which immunity, metabolism, microbiota composition, and environmental factors are closely interconnected, offering important perspectives for both basic research and the development of sustainable biocontrol and antimicrobial strategies. Full article

Acute non-typhoidal salmonellosis (NTS) from non-typhoidal Salmonella remains a major cause of foodborne bacterial gastroenteritis, and non-antibiotic interventions are needed to combat multidrug-resistant NTS. Bioactive compounds from edible mushroom extracts have shown both direct and indirect antimicrobial activities on Salmonella. However, the variation in their antimicrobial activity could be due to several factors, including the extract’s form and strain. This study investigated the ability of crude exopolysaccharides (EPs) produced by Schizophyllum commune CMU-01 to limit Salmonella infection in vitro. Agar well diffusion and liquid culture were used to determine the direct anti-Salmonella activity of S. commune EPs, while the gentamicin protection assay and qPCR in human gut epithelium (T84 cells) and murine macrophages (RAW264.7 cells) were used to investigate its indirect (immunomodulatory) activity. Our data reveal that S. commune EPs do not confer the direct antimicrobial property against Salmonella. However, its immunomodulatory activity in two important components of the gut innate defense (the gut epithelium and macrophages) against Salmonella infection has been demonstrated. S. commune EPs reduce Salmonella gut epithelial cell invasion and activate macrophages toward M1 (inflammatory phenotype) polarization, resulting in the reduction in intracellular Salmonella burdens. Alterations in proinflammatory and anti-inflammatory cytokine gene expressions were also detected in S. commune EPs-treated cells. These findings suggest that the host innate immune response to fungal exopolysaccharides derived from S. commune CMU-01 favors reducing Salmonella proliferation within host cells by altering the expression levels of proinflammatory cytokines. Full article