Search Results (8,349)

Digital twins (DTs), virtual replicas that integrate mechanistic modeling with real-time clinical data, are emerging as powerful tools in healthcare with particular promise in pediatrics, where age-dependent physiology and ethical considerations complicate infectious disease management. This narrative review examines current and potential applications of DTs across antimicrobial stewardship (AMS), diagnostics, vaccine personalization, respiratory support, and system-level preparedness. Evidence indicates that DTs can optimize antimicrobial therapy by simulating pharmacokinetics and pharmacodynamics to support individualized dosing, enable Bayesian therapeutic drug monitoring, and facilitate timely de-escalation. They also help guide intravenous-to-oral switches and treatment durations by integrating host-response markers and microbiological data, reducing unnecessary antibiotic exposure. Diagnostic applications include simulating host–pathogen interactions to improve accuracy, forecasting clinical deterioration to aid in early sepsis recognition, and differentiating between viral and bacterial illness. Immune DTs hold potential for tailoring vaccination schedules and prophylaxis to a child’s unique immune profile, while hospital- and system-level DTs can simulate outbreaks, optimize patient flow, and strengthen surge preparedness. Despite these advances, implementation in routine pediatric care remains limited by challenges such as scarce pediatric datasets, fragmented data infrastructures, complex developmental physiology, ethical concerns, and uncertain regulatory frameworks. Addressing these barriers will require prospective validation, interoperable data systems, and equitable design to ensure fairness and inclusivity. If developed responsibly, DTs could redefine pediatric infectious disease management by shifting practice from reactive and population-based toward proactive, predictive, and personalized care, ultimately improving outcomes while supporting AMS and health system resilience. Full article

This study explores tomato agri-food residues as sources of bacteria with bioprotective potential to enhance product shelf-life and safety. A total of 245 bacterial strains were isolated, comprising predominantly Pseudomonas (52%) and Bacillus (44%) spp., with lactic acid bacteria (LAB) present at lower levels (4%). The antimicrobial activity of these isolates was assessed against pathogenic and spoilage bacteria and phytopathogenic molds. Notably, the Bacillus isolate TRB1-7 exhibited moderate activity against L. monocytogenes (inhibition halo diameter: 10.64 mm), while Pseudomonas and LAB isolates showed limited or no inhibition. Antifungal assays highlighted significant antifungal potential for Bacillus isolates. Results showed that 16% and 15% of the 245 isolates inhibited F. oxysporum and C. acutatum growth, respectively. Nine of these isolates underwent acid-adaptation and were evaluated against the selected molds using Potato Dextrose Agar (PDA) at pH 4.0 to simulate tomato conditions. Only isolate BRZ3-2, identified as B. aerius, was adapted to acidic conditions and inhibited F. oxysporum by 25%. Experiments on tomato-based agar at the same pH showed no inhibition by Bacillus isolates. These results suggest that tomato microbiota harbors acid-tolerant Bacillus strains with potential for post-harvest bio-preservation. Further studies on strains TRB1-7 and BRZ3-2 are required to develop effective bioprotective applications. Full article

Silver nanoparticles (AgNPs) synthesized by ‘green’ methods using plant extracts have emerged as promising antimicrobial agents for combating soilborne pathogens. In this study, the antimicrobial activity of four AgNP formulations prepared using various reducing agents (AgNP#1, AgNP#2, AgNP#3, AgNP#4) against sanitary-indicator bacteria (Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29213, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853) and phytopathogenic Pseudomonas syringae strains isolated from Zea mays plants was estimated. The results demonstrated that AgNP#3 and AgNP#4 exhibited the greatest antibacterial efficacy, with minimal inhibitory concentrations (MIC). The soil incubation studies confirmed that AgNPs reduced the population of P. syringae without significant effects on beneficial soil microbiota. AgNP#1 and AgNP#2 exhibited a stimulatory effect on the Zea mays seed germination, bringing out their potential for agricultural applications. Thus, the developed biogenic AgNPs could serve as efficient antimicrobial agents for sustainable soil sanitation while minimizing environmental risks. Full article

The increasing prevalence of antimicrobial resistance (AMR) among foodborne pathogens has emerged as a critical global health concern, undermining the efficacy of conventional antimicrobial agents and threatening the safety and integrity of the food supply chain. In response, probiotics, prebiotics, and their combinations as synbiotics are increasingly recognised as sustainable, health-oriented strategies to mitigate AMR across the food chain. Probiotics—live microorganisms that, when administered in adequate amounts, confer health benefits to the host—contribute to AMR mitigation through multiple mechanisms, including competitive exclusion of resistant pathogens, production of antimicrobial metabolites (e.g., bacteriocins and organic acids), modulation of host immunity, and restoration of gut microbial balance. Prebiotics, defined as non-digestible food ingredients, selectively stimulate the growth and/or metabolic activity of beneficial bacteria such as Lactobacillus and Bifidobacterium spp., thereby reinforcing colonisation resistance. When combined as synbiotics, these agents may exert synergistic effects, enhancing microbial resilience, promoting gut health, and reducing the colonisation and persistence of AMR-related pathogens. The integration of these bio-based approaches into food systems—particularly in the development of fermented and functional foods—supports broader One Health objectives by reducing the need for antibiotics and contributing to global AMR containment efforts. This review summarises current scientific insights, explores practical applications, and outlines future perspectives on the role of probiotics, prebiotics, and synbiotics in combating AMR throughout the food chain. Full article

The proteasome is a central proteolytic complex that maintains protein homeostasis by eliminating damaged, misfolded, and regulatory proteins. Beyond this quality control role, it generates bioactive peptides that contribute to immune surveillance, intracellular signaling, neuronal communication, and antimicrobial defense. Proteolysis is mediated by the catalytic β1, β2, and β5 subunits, traditionally defined by caspase-like, trypsin-like, and chymotrypsin-like activities. However, these sites display overlapping and flexible specificities, enabling cleavage after nearly all amino acids. This review focuses on proteasome catalytic activity, with particular emphasis on the biochemical and structural features of the catalytic subunits that define cleavage selectivity. We first provide a historical overview of the discovery of proteolytic activities and trace the evolutionary diversification of subunits that gave rise to specialized variants such as the immunoproteasome, thymoproteasome, intermediate proteasomes, and the spermatoproteasome. We then highlight how advances in computational modeling and structural biology have refined our understanding of cleavage preferences. In addition, we examine how regulatory particles, post-translational modifications, and physiological conditions, including inflammation, oxidative stress, and aging, modulate proteolytic activity. Finally, we discuss the development of selective inhibitors targeting individual catalytic sites, emphasizing their therapeutic potential in cancer, autoimmunity, and infectious disease, and outline future directions for the field. Full article

Antibiotics have been traditionally used to treat patients with infectious diseases. However, recent investigations have highlighted their immunomodulating features. Additionally, they have been used to treat patients with rheumatologic diseases of proven infectious etiology. Thus, an emerging body of literature is developing on the potential role of antibiotics in managing patients with rheumatologic diseases, which are primarily characterized by autoimmune-driven inflammation. We critically review the potential use of antibiotics in rheumatology, focusing on both their direct antimicrobial actions and immunomodulatory effects. We also examine the potential clinical applications, underlying pharmacological mechanisms, controversies, and future research directions. Databases of biomedical research (PubMed, Scopus, Web of Science, and Cochrane) and Google Scholar were searched. The critical evaluation of the available data suggests that antibiotics should be used only for patients with rheumatologic diseases with a clear infectious etiology. These indications are the treatment and prevention of recurrence of rheumatic fever, Whipple’s disease, and early Lyme disease. Additionally, antibiotics may be considered for early administration in patients with reactive arthritis. Until data from robust clinical trials support the consideration of antibiotics in other rheumatologic diseases, beyond those with a clear infectious etiology, clinicians should follow the internationally relevant guidelines and avoid their use in treating such diseases in this patient population. Further studies may offer additional data for using antibiotics in treating patients with additional rheumatologic diseases, especially in cases where conventional treatments have inadequate effectiveness or are associated with considerable adverse events. Full article

Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA’s antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for periprosthetic joint infection caused by methicillin-resistant Staphylococcus aureus (MRSA-PJI) are limited by considerable side effects, such as high costs and the development of resistance. Therefore, there is an urgent need to explore novel alternative or adjunctive therapies. This review provides a comprehensive overview of several innovative therapeutic strategies. These include monoclonal antibody therapies that target specific bacterial components; phage therapy, which can either independently or synergistically degrade biofilms and enhance antimicrobial efficacy, characterized by its high specificity; antimicrobial peptides, capable of disrupting bacterial membrane integrity and exhibiting dual antibiofilm activity, with a reduced tendency to induce resistance; and nanoparticles and hydrogels, which function as drug delivery systems for sustained release, thereby improving both preventive and therapeutic outcomes. However, these novel therapies also face challenges such as high production costs and limited stability, underscoring the need for further research and optimization. Future efforts should focus on additional studies, clinical trials, and the development of robust regulatory frameworks to fully realize the potential of these treatments for MRSA-PJI. Full article

Coxiella burnetii, the causative agent of human Q fever, subverts macrophage antimicrobial functions to establish an intracellular replicative niche. To better understand host–pathogen interactions, we investigated the transcriptional responses of human alveolar macrophages (hAMs) infected with virulent [NMI, G (Q212)], attenuated (NMII), and avirulent (Dugway) strains of C. burnetii. RNA sequencing indicated that all strains activated proinflammatory pathways, particularly IL-17 signaling, though the magnitude and nature of the response varied by strain. Infections with NMI, NMII or G (Q212) resulted in differential expression of roughly the same number of genes, while Dugway infection induced a stronger transcriptional response. Dugway and G (Q212) tended to polarize macrophages toward M1-like states, whereas responses to NMI and NMII were variable. Cytokine assays of NMII-infected THP-1 macrophages suggested the activation of IL-17 signaling, but only at later stages of infection, and single-cell RNA sequencing of NMII-infected THP-1 macrophages indicated heterogeneity in host response to infection, with distinct subpopulations exhibiting M1-like and M2-like inflammatory profiles. These findings highlight the complexity of macrophage response to C. burnetii and underscore the importance of strain-specific and cell-specific factors in shaping host immunity. Understanding these dynamics may inform the development of targeted therapies for Q fever. Full article

Pseudomonas aeruginosa causes ocular and other infections and quickly acquires antimicrobial resistance. Polymyxin B and colistin are last-line agents against resistant P. aeruginosa, yet even resistance to these is increasing. Antimicrobial peptides (AMPs) are also being developed as new antibiotics, but resistant mechanisms to polymyxins might also cause resistance to these AMPs. This study evaluated whether isolates with differing polymyxin resistances also showed elevated minimum inhibitory concentrations (MICs) to the human cathelicidin LL-37 and a synthetic AMP, Mel4. Forty isolates of P. aeruginosa, mostly collected in India and Australia, were assessed for minimum inhibitory concentrations (MICs) by broth microdilution in cation-adjusted Mueller–Hinton broth. Whole genome sequences were analyzed using NCBI BLAST (version 2.17.0). SNPs vs. MIC associations were evaluated with Fisher’s exact test. Sixty-five percent of isolates were resistant to polymyxin B, and 80% to colistin. Polymyxin B MICs ranged from 0.5 to 512 µg/mL, with 32.5% showing intermediate resistance and 22.5% being highly resistant (MIC ≥ 256 µg/mL). MICs for polymyxin B and colistin were strongly correlated with each other (Spearman’s R ≥ 0.6; n = 40; p ≤ 0.001). LL-37 showed moderate correlations with polymyxin B, colistin, and Mel4, whereas Mel4 showed weaker correlations with polymyxin B or colistin (R < 0.4). Genomic analysis identified SNPs in mipB (V469M, G441S) as being associated with the MICs to all the antimicrobials. Strains with MICs between 64 and 512 µg/mL were significantly more likely to harbor nalC (E153Q/D) or the mipB variants (p < 0.05). Higher polymyxin MICs were associated with elevated MICs to LL-37 and, to a lesser extent, Mel4, suggesting partial shared resistance among membrane active peptides. Defining the effect of the SNPs and clinical relevance of AMP cross-resistance may inform future therapies and safer contact lenses. Full article

NADESs represent a modern class of extraction media that align with the principles of green chemistry. They are considered non-toxic and biodegradable, but relatively little is known about their biological activity. This study investigated the antioxidant, antibacterial, and antifungal properties of 40 NADESs. The systems were developed from primary (PRIM) based on choline chloride (ChCl), and specialized (HEVO) plant-derived metabolites, particularly based on thymol and menthol. Their antioxidant activity was evaluated using spectrophotometric tests. The antimicrobial activity was evaluated by the disk diffusion method. The data obtained were analyzed using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). NADESs based on PRIM exhibited negligible antioxidant activity and relatively low antimicrobial activity. By contrast, NADESs containing HEVO, particularly thymol-based systems, indicated significant antioxidant activity, with stronger activity observed at higher molar proportions of thymol. In the 1,8-cineole:thymol system, ABTS activity ranged from 167.37 ± 24.17 to 861.25 ± 33.03 mg Trolox equivalents/mL NADES (molar ratios 9:1 and 1:9, respectively). The 1,8-cineole:thymol system (1:9) also showed strong antimicrobial activity, with a maximum inhibition zone of 39.33 ± 2.52 mm against Staphylococcus aureus. In summary, NADESs based on HEVO exhibit significantly stronger biological activity than those containing only PRIM. Full article

Bacterial diseases cause significant economic losses and pose a major challenge to global crop yields. These diseases reduce yields and affect food security, particularly for small-scale farmers in developing regions. Post-harvest losses also contribute to resource waste, soil degradation, and deforestation. Conventional management strategies, such as synthetic fungicides and antimicrobials, raise concerns about environmental sustainability, human health, and pathogen resistance. Bacteriophages—viruses that selectively infect bacterial pathogens—offer a highly specific and eco-friendly alternative for disease management both post-harvest and pre-harvest, reducing the need for chemical pesticides throughout the plant lifecycle. This review examines bacteriophage biology, advantages over traditional treatments, and challenges to their application. Phages effectively target pathogens such as Pectobacterium, Xanthomonas, Xylella, Clavibacter, and Dickeya, while preserving beneficial microorganisms. Key challenges include bacterial resistance, regulatory hurdles, and phage stability under environmental conditions. Advances in phage genomics, bioengineering, and formulation have enhanced viability and efficacy, supporting phages as promising biocontrol agents. Integrating phage therapy with other eco-friendly strategies may improve effectiveness further. Future research should focus on optimizing production, refining regulations, and large-scale field studies to ensure practical feasibility. Addressing these issues will help bacteriophages contribute significantly to sustainable plant disease management and global food security. Full article

Bats are widely recognized as reservoirs of diverse bacterial pathogens with important implications for human health. Recent zoonotic disease outbreaks have intensified interest in bat microbiomes, with high-throughput sequencing increasingly used to assess microbial diversity. In this article, we review literature from the past five years on bacterial species associated with bats and their potential clinical relevance. Using automated searches and manual filtering, we extracted data from 47 peer-reviewed studies. Most research has focused on guano samples, though interest in skin microbiomes is rising, particularly in relation to Pseudogymnoascus destructans, the agent of white-nose syndrome. China leads in the number of publications, followed by the United States, and amplicon sequencing remains the predominant metagenomic method. Across studies, 4700 bacterial species were reported, including several known human pathogens capable of aerosol transmission or opportunistic infections in immunocompromised individuals. Many of these taxa are classified as global priority targets for antimicrobial drug development by the World Health Organization and the U.S. Centers for Disease Control and Prevention. Given the clinical severity of diseases linked to some species, bats should be integrated into epidemiological surveillance systems. However, the lack of standardized reporting practices significantly limits the comparability and utility of bat microbiome data for robust ecological and epidemiological analyses. Full article

Background/Objectives: The increasing prevalence of multidrug-resistant Staphylococcus aureus represents a major clinical challenge, primarily driven by the acquisition of multiple resistance mechanisms. Among these, efflux pumps such as NorA play a pivotal role in quinolone resistance by promoting active drug extrusion and reducing intracellular antibiotic levels. This study evaluated the synthetic chalcone CMA4DMA as a potential NorA efflux pump inhibitor and modulator of bacterial resistance. Methods: Antimicrobial susceptibility assays were conducted against S. aureus SA1199 (wild-type) and SA1199B (NorA-overexpressing) strains. The minimum inhibitory concentration (MIC) of CMA4DMA and its modulatory effects on norfloxacin and ethidium bromide were determined. Efflux inhibition was assessed by ethidium bromide accumulation and SYTOX Green assays. Molecular docking and in silico ADMET analyses were performed to predict binding affinity and pharmacokinetic parameters. Results: CMA4DMA exhibited no intrinsic antibacterial activity (MIC ≥ 1024 µg/mL) but reduced the MIC of norfloxacin from 32 to 8 µg/mL and that of ethidium bromide from 32 to 8 µg/mL in SA1199. In SA1199B, reductions from 64 to 16 µg/mL and from 64 to 32 µg/mL were observed, respectively. Fluorescence increased by 15% without affecting membrane integrity. Docking revealed a binding affinity of −7.504 kcal/mol, stronger than norfloxacin (−7.242 kcal/mol), involving key residues Leu218, Ile309, Arg310, and Ile313. ADMET data indicated high intestinal absorption (88.76%) and permeability (Papp = 1.38 × 10⁻⁵ cm/s). Conclusions: CMA4DMA effectively restored norfloxacin susceptibility in resistant S. aureus strains, highlighting its potential as a promising scaffold for developing novel efflux pump inhibitors and antibiotic adjuvants. Full article

The fields of healthcare and pharmaceutical science are increasingly focused on developing innovative and effective treatments. This trend is driven by a growing consumer demand for natural, sustainable, and highly functional polymer-based products. This study focuses on two biomaterials: chitosan and royal jelly. Chitosan, a linear polysaccharide derived from chitin, is well-regarded for its hemostatic and antimicrobial properties, making it an excellent candidate for wound healing applications. Royal jelly, a nutrient-rich secretion from honeybees, represents a complex mixture of proteins, lipids, vitamins, and antioxidants, notably 10-hydroxy-2-decenoic acid (10-H2DA). It is known for its anti-inflammatory, antioxidant, and regenerative effects on the skin. While the individual benefits of chitosan and royal jelly are well-documented, there is a significant research gap concerning their synergistic application in various treatments such as topical formulations, wound healing, regenerative medicine, and delivery transport processes. Ultimately, this review concludes that the synergistic effects of chitosan and royal jelly could provide a material platform with a superior dual-action profile, integrating the structural and antimicrobial benefits of chitosan with the powerful regenerative and anti-inflammatory effects of royal jelly. This synergy strongly supports their utility in developing next-generation, high-performance natural bioproducts for wound healing, bone regeneration, agriculture, or aquaculture applications. Full article

Microfluidic paper-based analytical devices (µPADs) are ideal for point-of-care diagnostics due to their low cost, compact size, and ease of use. However, current designs have limited multiplexing capabilities, making it difficult to simultaneously detect pathogens and biomarkers in the same sample. In this work, we introduce NanoArrayPAD−X, a novel µPAD design that combines wax-printed microfluidic networks with an array of nanoprobes for the simultaneous detection of multiple targets. This is achieved by distributing the sample through the microfluidic network containing X detection areas. There, targets are captured through physical interactions and recognized by specific antibody-coated nanoprobes released from the nanoprobe array. This generates X dots whose color depends on the concentration of the targets in the sample. A NanoArrayPAD−5 platform capable of detecting five targets was developed to aid in the diagnosis of ventilator-associated pneumonia (VAP). The sensor array could detect Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and the inflammatory biomarker myeloperoxidase (MPO) with a total turnaround time of 25 min, which is faster than waiting for an overnight culture and the results of an ELISA. Notably, our prototype successfully detected the targets in 87 bronchial aspirate (BAS) specimens, thus demonstrating the suitability of the platform for analyzing complex samples with sputum-like qualities. These findings establish NanoArrayPAD−X as a promising tool for the rapid, multiplexed screening of respiratory pathogens and biomarkers, with potential for guiding personalized antimicrobial therapy in suspected cases of nosocomial pneumonia. Full article