Search Results (4,103)

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Biofilms are structured communities of microorganisms encased in a self-produced extracellular matrix, and they represent one of the most widespread forms of microbial life on Earth. Their presence poses serious challenges in both environmental and clinical settings. In natural and industrial systems, biofilms contribute to water contamination, pipeline corrosion, and biofouling. Clinically, biofilm-associated infections are responsible for approximately 80% of all microbial infections, including endocarditis, osteomyelitis, cystic fibrosis, and chronic sinusitis. A particularly critical concern is their colonization of medical devices, where biofilms can lead to chronic infections, implant failure, and increased mortality. Implantable devices, such as orthopedic implants, cardiac pacemakers, cochlear implants, urinary catheters, and hernia meshes, are highly susceptible to microbial attachment and biofilm development. These infections are often recalcitrant to conventional antibiotics and frequently necessitate surgical revision. In the United States, over 500,000 biofilm-related implant infections occur annually, with prosthetic joint infections alone projected to incur revision surgery costs exceeding USD 500 million per year—a figure expected to rise to USD 1.62 billion by 2030. To address these challenges, surface modification of medical devices has emerged as a promising strategy to prevent bacterial adhesion and biofilm formation. This review focuses on recent advances in chemical surface functionalization using non-antibiotic agents, such as enzymes, chelating agents, quorum sensing quenching factors, biosurfactants, oxidizing compounds and nanoparticles, designed to enhance antifouling and mature biofilm eradication properties. These approaches aim not only to prevent device-associated infections but also to reduce dependence on antibiotics and mitigate the development of antimicrobial resistance. Full article

In this study, a Z-scheme Ho₂InSbO₇/Ag₃PO₄ (HAO) heterojunction photocatalyst was successfully fabricated for the first time by ultrasound-assisted solvothermal method. The structural features, compositional components and morphological characteristics of the synthesized materials were thoroughly characterized by a series of techniques, including X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectrum, X-ray photoelectron spectroscopy, transmission electron microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. A comprehensive array of analytical techniques, including ultraviolet-visible diffuse reflectance absorption spectra, photoluminescence spectroscopy, time-resolved photoluminescence spectroscopy, photocurrent testing, electrochemical impedance spectroscopy, electron paramagnetic resonance, and ultraviolet photoelectron spectroscopy, was employed to systematically investigate the optical, chemical, and photoelectronic properties of the materials. Using oxytetracycline (OTC), a representative tetracycline antibiotic, as the target substrate, the photocatalytic activity of the HAO composite was assessed under visible light irradiation. Comparative analyses demonstrated that the photocatalytic degradation capability of the HAO composite surpassed those of its individual components. Notably, during the degradation process, the application of the HAO composite resulted in an impressive removal efficiency of 99.89% for OTC within a span of 95 min, along with a total organic carbon mineralization rate of 98.35%. This outstanding photocatalytic performance could be ascribed to the efficient Z-scheme electron-hole separation system occurring between Ho₂InSbO₇ and Ag₃PO₄. Moreover, the adaptability and stability of the HAO heterojunction were thoroughly validated. Through experiments involving the capture of reactive species and electron paramagnetic resonance analysis, the active species generated by HAO were identified as hydroxyl radicals (•OH), superoxide anions (•O₂⁻), and holes (h⁺). This identification provides valuable insights into the mechanisms and pathways associated with the photodegradation of OTC. In conclusion, this research not only elucidates the potential of HAO as an efficient Z-scheme heterojunction photocatalyst but also marks a significant contribution to the advancement of sustainable remediation strategies for OTC contamination. Full article

Background/Objectives: The rapid emergence of multidrug-resistant bacterial infections demands innovative non-antibiotic therapeutic strategies. Dual-modal photoresponse therapy integrating photodynamic (PDT) and photothermal (PTT) effects offers a promising rapid antibacterial approach, yet designing single-material systems with synergistic enhancement remains challenging. This study aims to develop uniform Cu-based metal–organic framework micrometer cubes (Cu-BN) for efficient PDT/PTT synergy. Methods: Cu-BN cubes were synthesized via a one-step hydrothermal method using Cu(NO₃)₂ and 2-amino-p-benzoic acid. The material’s dual-mode responsiveness to visible light (420 nm) and near-infrared light (808 nm) was characterized through UV–Vis spectroscopy, photothermal profiling, and reactive oxygen species (ROS) generation assays. Antibacterial efficacy against multidrug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was quantified via colony counting under dual-light irradiation. Results: Under synergistic 420 + 808 nm irradiation for 15 min, Cu-BN (200 μg/mL) achieved rapid eradication of multidrug-resistant E. coli (99.94%) and S. aureus (99.83%). The material reached 58.6 °C under dual-light exposure, significantly exceeding single-light performance. Photodynamic analysis confirmed a 78.7% singlet oxygen (¹O₂) conversion rate. This enhancement stems from PTT-induced membrane permeabilization accelerating ROS diffusion, while PDT-generated ROS sensitized bacteria to thermal damage. Conclusions: This integrated design enables spatiotemporal PDT/PTT synergy within a single Cu-BN system, establishing a new paradigm for rapid-acting, broad-spectrum non-antibiotic antimicrobials. The work provides critical insights for developing light-responsive biomaterials against drug-resistant infections. Full article

Biotechnological research increasingly focuses on developing new drugs to counter the rise of antibiotic-resistant strains in hospitals. This study aimed to create bacterial lysates from antibiotic-resistant pathogens isolated from patients and medical instruments across hospital departments. Identification was performed based on morphological, cultural, and biochemical characteristics, as well as 16S rRNA gene sequencing using the BLAST algorithm. Strain viability was assessed using the Miles and Misra method, while sensitivity to eight antibacterial drug groups and biosafety between cultures were evaluated using agar diffusion. From 15 clinical sources, 25 pure isolates were obtained, and their phenotypic and genotypic properties were studied. Carbohydrate fermentation testing confirmed that the isolates belonged to the genera Escherichia, Citrobacter, Klebsiella, Acinetobacter, Pseudomonas, Staphylococcus, Haemophilus, and Streptococcus. The cultures exhibited good viability (10⁹–10¹⁰ CFU/mL) and compatibility with each other. Based on prevalence and clinical significance, three predominant hospital pathogens (Klebsiella pneumoniae 12 BL, Pseudomonas aeruginosa 3 BL, and Acinetobacter baumannii 24 BL) were selected to develop a bacterial lysate consortium. Lysates were prepared with physical disruption using a French press homogenizer. The resulting product holds industrial value and may stimulate the immune system to combat respiratory pathogens prevalent in Kazakhstan’s healthcare settings. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background/Objectives: This study examines how seasonality, pollution, and sample type (water and sediment) influence the presence and distribution of antibiotic resistance genes (ARGs), with a focus on antibiotic resistance genes (ARGs) located on plasmids (the complete set of plasmid-derived sequences, including ARGs) in a tropical urban river. Methods: Samples were collected from three sites along a pollution gradient in the Virilla River, Costa Rica, during three seasonal campaigns (wet 2021, dry 2022, and wet 2022). ARGs in water and sediment were quantified by qPCR, and metagenomic sequencing was applied to analyze chromosomal and plasmid-associated resistance profiles in sediments. Tobit and linear regression models, along with multivariate ordination, were used to assess spatial and seasonal trends. Results: During the wet season of 2021, the abundance of antibiotic resistance genes (ARGs) such as sul-1, intI-1, and tetA in water samples decreased significantly, likely due to dilution, while intI-1 and tetQ increased in sediments, suggesting particle-bound accumulation. In the wet season 2022, intI-1 remained low in water, qnrS increased, and sediments showed significant increases in tetQ, tetA, and qnrS, along with decreases in sul-1 and sul-2. Metagenomic analysis revealed spatial differences in plasmid-associated ARGs, with the highest abundance at the most polluted site (Site 3). Bacterial taxa also showed spatial differences, with greater plasmidome diversity and a higher representation of potential pathogens in the most contaminated site. Conclusions: Seasonality and pollution gradients jointly shape ARG dynamics in this tropical river. Plasmid-mediated resistance responds rapidly to environmental change and is enriched at polluted sites, while sediments serve as long-term reservoirs. These findings support the use of plasmid-based monitoring for antimicrobial resistance surveillance in aquatic systems. Full article

Background/Objectives: Strengthening antimicrobial stewardship (AMS) programs is an invaluable intervention in the ongoing efforts to contain the threat of antimicrobial resistance (AMR), particularly in low-resource settings. This study evaluates the impact of the Telementoring, Education, and Advocacy Collaboration initiative for Health through Antimicrobial Stewardship (TEACH AMS), which uses the virtual Extension for Community Healthcare Outcomes (ECHO) learning model to enhance AMS capacity in Kenya, Ghana, and Malawi. Methods: A mixed-methods approach was used, which included attendance data collection, facility-level assessments, post-session and follow-up surveys, as well as focus group discussions. Results: Between September 2023 and February 2025, 77 virtual learning sessions were conducted, engaging 2445 unique participants from hospital-based AMS committees and health professionals across the three countries. Participants reported significant knowledge gain, and data showed facility improvements in two core AMS areas, including the implementation of multidisciplinary ward-based interventions/communications and enhanced monitoring of antibiotic resistance patterns. Along those lines, participants reported that the program assisted them in improving prescribing and culture-based treatments, and also evidence-informed antibiotic selection. The evidence of implementing ward-based interventions was further stressed in focus group discussions, as well as other strengthened practices like point-prevalence surveys, and development or revision of stewardship policies. Substantial improvements in microbiology services were also shared by participants, particularly in Malawi. Other practices mentioned were strengthened multidisciplinary communication, infection prevention efforts, and education of patients and the community. Conclusion: Our findings suggest that a virtual case-based learning educational intervention, providing structured and tailored AMS capacity building, can drive behavior change and strengthen healthcare systems in low resource settings. Future efforts should aim to scale up the engagements and sustain improvements to further strengthen AMS capacity. Full article

Genomic islands (GIs) including integrative and conjugative elements (ICEs), prophages, and integrative plasmids are central drivers of horizontal gene transfer in bacterial plant pathogens. These elements often carry cargo genes encoding virulence factors, antibiotic and metal resistance determinants, and metabolic functions that enhance environmental adaptability. In plant-pathogenic species such as Pseudomonas syringae, GIs contribute to host specificity, immune evasion, and the emergence of novel pathogenic variants. ICEclc and its homologs represent integrative and mobilizable elements whose tightly regulated excision and transfer are driven by a specialized transcriptional cascade, while ICEs in P. syringae highlight the ecological impact of cargo genes on pathogen virulence and fitness. Pathogenicity islands further modulate virulence gene expression in response to in planta stimuli. Beyond P. syringae, GIs in genera such as Erwinia, Pectobacterium, and Ralstonia underpin critical traits like toxin biosynthesis, secretion system acquisition, and topoisomerase-mediated stability. Leveraging high-throughput genomics and structural biology will be essential to dissect GI regulation and develop targeted interventions to curb disease spread. This review synthesizes the current understanding of GIs in plant-pathogenic gammaproteobacteria and outlines future research priorities for translating mechanistic insights into sustainable disease control strategies. Full article

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 $\mathsf{\mu }$m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable population. This was the objective behind this study. Methods: The medical records of all pediatric patients (under 12 years) admitted and treated with antibiotics at a Ghanaian Teaching Hospital between January 2022 and March 2022 were extracted from the hospital’s electronic database. The prevalence and appropriateness of antibiotic use were based on antibiotic choices compared with current guidelines. Influencing factors were also assessed. Results: Of the 410 admitted patients, 319 (77.80%) received at least one antibiotic. The majority (68.65%; n = 219/319) were between 0 and 2 years, and males (54.55%; n = 174/319). Ceftriaxone was the most commonly prescribed antibiotic (20.69%; n = 66/319), and most of the systemic antibiotics used belonged to the WHO Access and Watch groups, including a combination of Access and Watch groups (42.90%; n = 136/319). Neonatal sepsis (24.14%; n = 77/319) and pneumonia (14.42%; n = 46/319) were the most common diagnoses treated with antibiotics. Antibiotic appropriateness was 42.32% (n = 135/319). Multivariate analysis revealed ceftriaxone prescriptions (aOR = 0.12; CI = 0.02–0.95; p-value = 0.044) and surgical prophylaxis (aOR = 0.07; CI = 0.01–0.42; p-value = 0.004) were associated with reduced antibiotic appropriateness, while a pneumonia diagnosis appreciably increased this (aOR = 15.38; CI = 3.30–71.62; p-value < 0.001). Conclusions: There was high and suboptimal usage of antibiotics among hospitalized pediatric patients in this leading hospital. Antibiotic appropriateness was influenced by antibiotic type, diagnosis, and surgical prophylaxis. Targeted interventions, including education, are needed to improve antibiotic utilization in this setting in Ghana and, subsequently, in ambulatory care. Full article

Efflux is one of the key mechanisms used by Gram-negative bacteria to reduce internal antibiotic concentrations. These active transport systems recognize and expel a wide range of toxic molecules, including antibiotics, thereby contributing to reduced antibiotic susceptibility and allowing the bacteria to acquire additional resistance mechanisms. To date, unlike other resistance mechanisms such as enzymatic modification or target mutations/masking, efflux is challenging to detect and counteract in clinical settings, and no standardized methods are currently available to diagnose or inhibit this mechanism effectively. This review first outlines the structural and functional features of major efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. It then explores various strategies used to curb their activity, with a particular focus on efflux pump inhibitors under development, detailing their structural classes, modes of action, and pharmacological potential. We discuss the main obstacles to their development, including the structural complexity and substrate promiscuity of efflux mechanisms, the limitations of current screening methods, pharmacokinetic and tissue distribution issues, and the risk of off-target toxicity. Overcoming these multifactorial barriers is essential to the rational development of less efflux-prone antibiotics or of efflux pump inhibitors. Full article