Search Results (610)

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

Background: Antibacterial resistance (ABR) poses a major challenge to global health, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the prominent multidrug-resistant strains. MRSA has developed resistance through the expression of Penicillin-Binding Protein 2a (PBP2a), a key transpeptidase enzyme involved in bacterial cell wall biosynthesis. Objectives: The objective was to design and characterize a novel small-molecule inhibitor targeting PBP2a as a strategy to combat MRSA. Methods: We synthesized a new indole triazole conjugate (ITC) using eco-friendly and click chemistry approaches. In vitro antibacterial tests were performed against a panel of strains to evaluate the ITC antibacterial potential. Further, a series of in silico evaluations like molecular docking, MD simulations, free energy landscape (FEL), and principal component analysis (PCA) using the crystal structure of PBP2a (PDB ID: 4CJN), in order to predict the mechanism of action, binding mode, structural stability, and energetic profile of the 4CJN-ITC complex. Results: The compound ITC exhibited noteworthy antibacterial activity, which effectively inhibited the selected strains. Binding score and energy calculations demonstrated high affinity of ITC for the allosteric site of PBP2a and significant interactions responsible for complex stability during MD simulations. Further, FEL and PCA provided insights into the conformational behavior of ITC. These results gave the structural clues for the inhibitory action of ITC on the PBP2a. Conclusions: The integrated in vitro and in silico studies corroborate the potential of ITC as a promising developmental lead targeting PBP2a in MRSA. This study demonstrates the potential usage of rational drug design approaches in addressing therapeutic needs related to ABR. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article

As the most unstable crystalline form of calcium carbonate, vaterite is rarely found in nature due to being highly prone to phase transitions. However, its high specific surface area, excellent biocompatibility, and high solubility properties have led to a research boom and the following breakthroughs in the last two decades: (1) From primitive calculations and spectroscopic analyses to modern multidimensional research methods combining calculations and experiments, the crystal structure of vaterite has turned from early identifications in orthorhombic and hexagonal crystal systems to a complex polymorphic structure within the monoclinic crystal system. (2) The formation process of vaterite not only conforms to the classical crystal growth theory but also encompasses the nanoparticle aggregation theory, which incorporates the concepts of oriented nanoparticle assembly and mesoscale transformation. (3) Regardless of the conditions, the formation of vaterite depends on an excess of CO₃²⁻ relative to Ca²⁺, and its stability duration relates to preservation conditions. (4) Vaterite demonstrates significant value in biomedical applications—including bone repair scaffolds, targeted drug carriers, and antibacterial coating materials—leveraging its porous structure, high specific surface area, and exceptional biocompatibility. While it also shows utility in environmental pollutant adsorption and general coating technologies, the current research remains predominantly concentrated on its medical applications. Currently, the rapid transformation of vaterite presents the primary limitation for its industrial application. Future research should prioritize investigating its formation kinetics and stability. Full article

Vibrio parahaemolyticus is a pathogenic bacterium widely distributed in marine environments, posing significant threats to aquatic organisms and human health. The overuse and misuse of antibiotics has led to the development of multidrug- and pan-resistant V. parahaemolyticus strains. There is an urgent need for novel antibacterial therapies with innovative mechanisms of action. In this work, a genome-scale metabolic network model (GMSN) of V. parahaemolyticus, named VPA2061, was reconstructed to predict the metabolites that can be explored as potential drug targets for eliminating V. parahaemolyticus infections. The model comprises 2061 reactions and 1812 metabolites. Through essential metabolite analysis and pathogen–host association screening with VPA2061, 10 essential metabolites critical for the survival of V. parahaemolyticus were identified, which may serve as key candidates for developing new antimicrobial strategies. Additionally, 39 structural analogs were found for these essential metabolites. The molecular docking analysis of the essential metabolites and structural analogs further investigated the potential value of these metabolites for drug design. The GSMN reconstructed in this work provides a new tool for understanding the pathogenic mechanisms of V. parahaemolyticus. Furthermore, the analysis results regarding the essential metabolites hold profound implications for the development of novel antibacterial therapies for V. parahaemolyticus-related disease. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, wound healing, acne management, and cosmetic dermatology. Zeolites demonstrated broad-spectrum antibacterial and antifungal efficacy, enhanced antioxidant activity, and biocompatible drug delivery in various dermatological models. Formulations such as silver–sulfadiazine–zeolite composites, Zn–clinoptilolite for acne, and zeolite-integrated microneedles offer innovative avenues for targeted therapy. Zeolite-based systems represent a promising shift toward multifunctional, localized dermatologic treatments. However, further research into long-term safety, formulation optimization, and clinical validation is essential to transition these materials into mainstream therapeutic use. Full article

Pseudomonas aeruginosa biofilm formation is critical to antibiotic resistance and persistence. Targeting cyclic di-GMP (c-di-GMP) signaling, a master biofilm formation and virulence regulator, presents a promising strategy to combat resistant bacterial infections. Myricetin, a natural polyphenolic flavonoid with documented antimicrobial and anti-biofilm activities, may enhance antibiotic efficacy against Pseudomonas aeruginosa. This study evaluated the synergistic effects of myricetin combined with azithromycin, ciprofloxacin, or cefdinir against both standard and drug-resistant Pseudomonas aeruginosa strains. Antibacterial activity, biofilm disruption, and motility inhibition were experimentally assessed, while molecular dynamic (MD) simulations elucidated myricetin’s molecular mechanism of action. Our results suggested that myricetin synergistically potentiated all three antibiotics, reducing c-di-GMP synthesis by 28% (azithromycin), 57% (ciprofloxacin), and 30% (cefdinir). It enhanced bactericidal effects, suppressed biofilm formation, and impaired swimming, swarming, and twitching motility. Computational analyses revealed that myricetin binds allosterically to FimX very well, a key regulator in the c-di-GMP signaling pathway. Hence, myricetin may act as a c-di-GMP inhibitor, reversing biofilm-mediated resistance in Pseudomonas aeruginosa and augmenting antibiotic efficacy. This integrated experimental and computational approach provides a framework for developing anti-virulence and antibiotic combination therapies against recalcitrant Gram-negative pathogens. Full article

Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC₅₀ values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases. Full article

The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in the market. With the surge in the misuse of antibiotics, there was a drastic increase in the number of multidrug-resistant (MDR) and extensively drug-resistant bacterial strains, even to antibiotics like Methicillin and vancomycin, aggravating the healthcare scenario. The threat of MDR ESKAPE pathogens is particularly high in nosocomial infections, where biofilms formed by bacteria create a protective barrier that makes them highly resistant to antibiotics, complicating the treatment efforts. Scientists are looking at natural and sustainable solutions, as several studies have projected deaths contributed by drug-resistant bacteria to go beyond 50 million by 2050. Many plant-derived metabolites have shown excellent antibacterial and antibiofilm properties that can be tapped for combating superbugs. The present review explores the current status of various studies on antibacterial plant metabolites like alkaloids and flavonoids and their mechanisms in disrupting biofilms and killing bacteria by way of inhibiting key survival strategies of bacteria like motility, quorum-sensing, reactive oxygen species production, and adhesion. These mechanisms were found to be varied in Gram-positive, Gram-negative, and acid-fast bacteria like Mycobacterium tuberculosis, which will be discussed in detail. The successful tapping of the benefits of such plant-derived chemicals in combination with evolving techniques of nanotechnology and targeted drug delivery can go a long way in achieving the goal of One Health, which advocates the unity of multiple practices for the optimal health of people, animals, and the environment. Full article

Clostridioides difficile is a leading pathogen involved in healthcare-associated diarrhea. With its increasing incidence, mortality, and antibiotic resistance, there is an urgent need for novel therapeutic strategies to address the infection and prevent its recurrence. Gegen Qinlian Decoction (GQD) is a traditional Chinese medicine for the treatment of diarrhea, but its main active ingredient is not known. Therefore, in this study, we evaluated the biological activity of berberine (BER) and baicalein (BAI), key components of GQD, against C. difficile. Time–kill curves and scanning electron microscopy were employed to assess their effects on C. difficile growth, while Enzyme-Linked Immunosorbnent Assay (ELISA) and cytotoxicity assays were used to examine their impact on toxin production. We also employed Quantitative Reverse Transcription PCR (qRT-PCR) to examine how BER and BAI influenced the expression of toxin-associated genes. At sub-inhibitory concentrations, these compounds exerted antibacterial activity against C. difficile by disrupting the integrity of the cell membrane and cell wall. Furthermore, BER and BAI also suppressed toxin production, demonstrating effects comparable to those of vancomycin. This suppression likely resulted from their bactericidal activity and the inhibition of toxin gene expression. This study not only highlights the potential application of GQD in treating C. difficile infections but also offers promising options for developing drugs targeting the growth and virulence of this pathogen. C. difficile infection (CDI) is a leading cause of severe diarrhea, and its treatment remains challenging due to limited drug options and its high recurrence rate. BAI and BER, the main active components of the traditional Chinese medicinal formula GQD, inhibited the growth of C. difficile by disrupting its cellular structure and significantly reduced the production of toxins associated with disease severity. Furthermore, the effects of BAI and BER on C. difficile were comparable to those of conventional antibiotics, suggesting that these compounds could be potential alternative therapies for CDI. This study not only highlights the therapeutic potential of GQD in treating CDI but also provides a replicable research strategy for the development of novel anti-CDI agents. Full article

Nanotechnology has revolutionized dermocosmetic innovation by improving the stability, bioavailability, and efficacy of active ingredients. In this study, we developed and optimized a novel xanthan gum-based hydrogel containing quercetin-loaded chitosan lactate nanoparticles for antioxidant and antimicrobial skincare applications. Chitosan was converted to its lactate form to enhance water solubility and enable nanoparticle formation at physiological pH via ionic gelation with citric acid. The formulation was optimized using Box–Behnken response surface methodology to achieve minimal particle size and maximal zeta potential. The final gel was structured with xanthan gum as the gelling polymer, into which the optimized nanoparticles were incorporated to create a stable and bioactive hydrogel system. Encapsulation efficiency was measured separately to assess the effectiveness of drug loading. The optimized nanoparticles exhibited a mean diameter of 422.02 nm, a zeta potential of +29.49 mV, and a high quercetin encapsulation efficiency (76.9%), corresponding to the proportion of quercetin retained in the nanoparticle matrix relative to the total amount initially used in the formulation. Antioxidant assays (TAC, DPPH, and reducing power) confirmed superior radical-scavenging activity of the nanoformulation compared to the base hydrogel. Antibacterial tests showed strong inhibition against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, with MIC values comparable to streptomycin. Accelerated stability studies demonstrated excellent physicochemical and microbiological stability over 60 days. This natural, bioactive, and eco-friendly formulation represents a promising platform for next-generation cosmeceuticals targeting oxidative stress and skin-related pathogens. Full article

Kasugamycin (KSM) is easily affected by photolysis, acid–base destruction, and oxidative decomposition in the natural environment, leading to its poor durability and low effective utilization rate, which affects its control effect on plant bacterial diseases. Nanomaterials modified with environment-responsive agents enable the control of the release of pesticides through intelligently responding to external stimuli, thereby improving efficacy and reducing environmental impact. In this study, a pH-responsive controlled release system was constructed using zeolitic imidazolate frameworks (ZIF-93) for the sustained and targeted delivery of KSM. The synthesized KSM@ZIF-93 exhibited a diameter of 63.93 ± 11.19 nm with a drug loading capacity of 20.0%. Under acidic conditions mimicking bacterial infection sites, the Schiff base bonds and coordination bonds in ZIF-93 dissociated, triggering the simultaneous release of KSM and Zn²⁺, achieving a synergistic antibacterial effect. Light stability experiments revealed a 34.81% reduction in UV-induced degradation of KSM when encapsulated in ZIF-93. In vitro antimicrobial assays demonstrated that KSM@ZIF-93 completely inhibited Erwinia amylovora at 200 mg/L and had better antibacterial activity and persistence than KSM and ZIF-93. The field experiment and safety evaluation showed that the control effect of KSM@ZIF-93 on pear fire blight at the concentration of 200 mg/L was (75.19 ± 3.63)% and had no toxic effect on pollen germination. This pH-responsive system not only enhances the stability and bioavailability of KSM but also provides a targeted and environmentally compatible strategy for managing bacterial infections during the flowering period of pear trees. Full article

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

Chronic wounds, such as diabetic ulcers and pressure injuries, remain a major global health burden, affecting over 40 million people worldwide and imposing significant socioeconomic strain. Hydrogel-based wound dressings have gained clinical attention for their ability to maintain moisture, mimic the extracellular matrix, and support tissue regeneration. However, traditional hydrogels often lack the mechanical robustness, antimicrobial efficacy, and dynamic responsiveness needed to treat complex wound environments effectively. To address these limitations, nanohybrid hydrogels, composite systems that integrate functional nanomaterials into hydrogel matrices, have emerged as intelligent platforms for advanced wound care. These systems enable multifunctional therapeutic action, including antibacterial activity, antioxidant regulation, angiogenesis promotion, immune modulation, and stimuli-responsive drug delivery. This review synthesizes recent advances in nanohybrid hydrogel design, beginning with an overview of traditional polymeric systems and their constraints. We categorize functional mechanisms according to biological targets and classify nanohybrid architectures by material type, including metal-based nanoparticles, nanozymes, carbon-based nanomaterials, polymeric nanogels, and metal–organic frameworks. Representative studies are summarized in a comparative table, and challenges related to biosafety, clinical translation, and design optimization are discussed. Nanohybrid hydrogels represent a rapidly evolving frontier in wound care, offering bioresponsive, multifunctional platforms with the potential to transform chronic wound management. Full article