Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance.

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Ginkgo biloba L. exocarp petroleum ether extract inhibits methicillin-resistant Staphylococcus aureus by modulating ion transport, virulence, and biofilm formation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.

Ca-doping interfacial engineering and glycolysis enable rapid charge separation for efficient phototherapy of MRSA-infected wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02 % is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.

Influence of chitosan and hydroxyethyl cellulose modifications towards the design of cross-linked double networks hydrogel for diabetic wound healing.

The wound dressings' lack of antioxidant and antibacterial properties, and delayed wound healing limit their use in wound treatment and management. Recent advances in dressing materials are aimed at improving the limitations discussed above. Therefore, the aim of this study includes the preparation and characterization of oxidized hydroxyethyl cellulose (OHEC) and ferulic acid-grafted chitosan (CS-FA) hydrogel loaded with green synthesized selenium nanoparticles (Se NPs) (OHEC-CS-FA-Se NPs named as nanohydrogel) for diabetic wound healing. The structure and properties of the hydrogel was characterized by FTIR, FE-SEM, HR-TEM, EDAX, UV-Vis spectrophotometry, XRD, DLS, zeta potential and rheological studies. The findings of these experiments demonstrate that nanohydrogel possesses a variety of outstanding qualities, including an optimal gel time, good swelling characteristics, a fair water retention rate, a good degradation rate, and strong mechanical stability. Nanohydrogel has been shown to have a synergistic impact by significantly increasing antioxidant activity by scavenging ABTS and DPPH radicals. The nanohydrogel's strong biocompatibility was confirmed by cytocompatibility testing using L929 mouse fibroblast cells. In addition, the wound healing potential of nanohydrogel was tested on L929 cells by an in vitro scratch assay and the nanohydrogel showed a wound closure rate of 100 % after 12 h. In addition to this study, nanohydrogel has demonstrated significant antimicrobial properties against human and wound infection causing pathogens such as Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. In the animal model, almost complete diabetic wound healing was achieved on day 14 after application of the nanohydrogel. The results obtained indicate that the multifunctional bioactive nature of OHEC-CS-FA-Se NPs showed exceptional antioxidant and antibacterial potential for the treatment of infected and chronic wounds.

Design of a Novel Lysine Isopeptide 1018KI11 with Potent Antimicrobial Activity as a Safe and Stable Food Preservative Candidate.

Antimicrobial peptides are potent food additive candidates, but most of them are sensitive to proteases, which limits their application. Therefore, we substituted arginine for lysine and introduced a lysine isopeptide bond to peptide IDR-1018 in order to improve its enzymatic stability. Subsequently, the protease stability and antimicrobial/antibiofilm activity of the novel peptides (1018K2-1018KI11) were investigated. The data revealed that the antienzymatic potential of 1018KI11 to bromelain and papain increased by 2-8 folds and 16 folds, respectively. The minimum inhibitory concentration (MIC) of 1018KI11 against methicillin-resistant Staphylococcus aureus (MRSA) ATCC43300 and Escherichia coli (E. coli) ATCC25922 was reduced 2-fold compared to 1018K11. Mechanism exploration suggested that 1018KI11 was more effective than 1018K11 in disrupting the cell barrier and damaging genomic DNA. Additionally, 1018KI11 at certain concentration conditions (2-64 µg/mL) reduced biofilm development of MRSA ATCC43300 by 4.9-85.9%. These data indicated that novel peptide 1018KI11 is a potential food preservative candidate.

Antimicrobial carbon dots/pectin-based hydrogel for promoting healing processes in multidrug-resistant bacteria-infected wounds.

Multidrug-resistant (MDR) bacterial infections have become a significant threat to global healthcare systems. Here, we developed a highly efficient antimicrobial hydrogel using environmentally friendly garlic carbon dots, pectin, and acrylic acid. The hydrogel had a porous three-dimensional network structure, which endowed it with good mechanical properties and compression recovery performance. The hydrogel could adhere closely to skin tissues and had an equilibrium swelling ratio of 6.21, indicating its potential as a wound dressing. In particular, the bactericidal efficacy following 24-h contact against two MDR bacteria could exceed 99.99 %. When the hydrogel was applied to epidermal wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) on mice, a remarkable healing rate of 93.29 % was observed after 10 days. This was better than the effectiveness of the traditionally used antibiotic kanamycin, which resulted in a healing rate of 70.36 %. In vitro cytotoxicity testing and hemolysis assay demonstrated a high biocompatibility. This was further proved by the in vivo assay where no toxic side effects were observed on the heart, liver, spleen, lung, or kidney of mice. This eco-friendly and easy-to-prepare food-inspired hydrogel provides an idea for the rational use of food and food by-products as a wound dressing to control MDR bacterial infections.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Capsicum annuum Oleoresin Nanoemulgel - Design Characterization and In vitro Investigation of Anticancer and Antimicrobial Activities.

BACKGROUND: The use of naturally occurring bioactive materials is getting great attention owing to their safety and environmental properties. Oily compounds, known as oleoresins, are expected to provide an important source for the natural products industry aiming to develop novel treatments for skin conditions. In this work, Capsicum annuum oleoresin nanoemulgel formulations have been prepared and investigated for their antibacterial and anticancer properties. METHODOLOGY: Several C. annuum oleoresin nanoemulgel formulations were prepared by incorporating a Carbopol 940 gel in a self-nanoemulsifying nanoemulsion consisting of C. annuum, tween 80, and span 80. The systems were characterized for particle size, polydispersity index (PDI), zeta potential, and rheology. The in vitro antimicrobial and cytotoxic activities of the optimum formulation were evaluated. RESULTS: The selected formulation is composed of 40% tween, 10% span 80, and 40% C. annuum oleoresin. This formulation produced a stable nanoemulsion with a narrow PDI value of 0.179 ± 0.08 and a droplet size of 104.0 ± 2.6 nm. Results of the in vitro antimicrobial studies indicated high potency of the systems against methicillin-resistant Staphylococcus aureus (MRSA) (zone of inhibition of 29 ± 1.9 mm), E. coli (33 ± 0.9 mm), K. pneumonia (30 ± 1.4 mm), and C. albicans (21 ± 1.5 mm), as compared to the reference antibiotic, ampicillin (18 ± 1.4 mm against K. pneumonia), and antifungal agent, fluconazole (12 ± 0.1 mm against C. albicans). Furthermore, cytotoxicity results, expressed as IC50 values, revealed that the oleoresin and its nanoemulgel had the best effects against the HepG2 cell line (IC50 value of 79.43 µg/mL for the nanoemulgel) and MCF7 (IC50 value of 57.54 µg/mL), and the most potent effect was found against 3T3 (IC50 value of 45.7 µg/m- L). On the other side, the system did not substantially exhibit activity against By-61 and Hela. CONCLUSION: C. annuum oleoresin and its nanoemulgel can be considered valuable sources for the discovery of new antibacterial, antifungal, and anticancer compounds in the pharmaceutical industry, especially due to their potent activity against various cancer cell lines as well as bacterial and fungal strains.

Antimicrobial photodynamic therapy with Brazilian green propolis controls intradermal infection induced by methicillin-resistant Staphylococcus aureus and modulates the inflammatory response in a murine model.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of skin and soft tissue infections worldwide. This microorganism has a wide range of antibiotics resistance, a fact that has made the treatment of infections caused by MRSA difficult. In this sense, antimicrobial photodynamic therapy (aPDT) with natural products has emerged as a good alternative in combating infections caused by antibiotic-resistant microorganisms. The objective of the present study was to evaluate the effects of aPDT with Brazilian green propolis against intradermal MRSA infection in a murine model. Initially, 24 Balb/c mice were infected intradermally in the ears with 1.5 × 108 colony-forming units of MRSA 43300. After infection, they were separated into 4 groups (6 animals per group) and treated with the vehicle, only Brazilian green propolis, only blue LED light or with the aPDT protocol (Brazilian green propolis + blue LED light). It was observed in this study that aPDT with Brazilian green propolis reduced the bacterial load at the site of infection. Furthermore, it was able to inhibit weight loss resulting from the infection, as well as modulate the inflammatory response through greater recruitment of polymorphonuclear cells/neutrophils to the infected tissue. Finally, aPDT induced an increase in the cytokines IL-17A and IL-12p70 in the draining retromaxillary lymph node. Thus, aPDT with Brazilian green propolis proved to be effective against intradermal MRSA infection in mice, reducing bacterial load and modulating the immune response in the animals. However, more studies are needed to assess whether such effects are repeated in humans.

Carriage of methicillin-resistant Staphylococcus aureus in children <6 years old: a retrospective follow-up study of the natural course and effectiveness of decolonization treatment.

BACKGROUND: Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach). OBJECTIVES: To investigate a wait-and-see approach in children 2-5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old. PATIENTS AND METHODS: In this retrospective follow-up study, we included MRSA carriers <6 years old in the Capital Region of Denmark from 2007 to 2021. Data were collected from laboratory information systems and electronic patient records. We divided children into age groups of <2 years or 2-5 years and decolonization treatment versus no treatment. Treatment was chlorhexidine body washes and nasal mupirocin, sometimes supplemented with systemic antibiotics. Children were followed until becoming MRSA free, or censoring. The probability of becoming MRSA free was investigated with Cox regression (higher HRs indicate faster decolonization). RESULTS: Of 348 included children, 226 were <2 years old [56/226 (25%) received treatment] and 122 were 2-5 years old [90/122 (74%) received treatment]. Multivariable analyses did not show a larger effect of decolonization treatment versus no treatment in <2-year-olds (HR 0.92, 95% CI 0.52-1.65) or 2-5-year-olds (HR 0.54, 95% CI 0.26-1.12). Without treatment, 2-5-year-olds tended to clear MRSA faster than <2-year-olds (HR 1.81, 95% CI 0.98-3.37). CONCLUSIONS: We did not find a larger effect of decolonization treatment versus no treatment in children <6 years old, and 2-5-year-olds tended to become MRSA free faster than <2-year-olds. These results support a wait-and-see approach for all children <6 years old, but further studies are needed.

Critical Evaluation of Green Synthesized Silver Nanoparticles-Kaempferol for Antibacterial Activity Against Methicillin-Resistant Staphylococcus aureus.

Introduction: This study aimed to characterize silver nanoparticles-kaempferol (AgNP-K) and its antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Green synthesis method was used to synthesize AgNP-K under the influence of temperature and different ratios of silver nitrate (AgNO3 and kaempferol). Methods: AgNP-K 1:1 was synthesized with 1 mM kaempferol, whereas AgNP-K 1:2 with 2 mM kaempferol. The characterization of AgNP-K 1:1 and AgNP-K 1:2 was performed using UV-visible spectroscopy (UV-Vis), Zetasizer, transmission electron microscopy (TEM), scanning electron microscopy-dispersive X-ray spectrometer (SEM-EDX), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. The antibacterial activities of five samples (AgNP-K 1:1, AgNP-K 1:2, commercial AgNPs, kaempferol, and vancomycin) at different concentrations (1.25, 2.5, 5, and 10 mg/mL) against MRSA were determined via disc diffusion assay (DDA), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) assay, and time-kill assay. Results: The presence of a dark brown colour in the solution indicated the formation of AgNP-K. The UV-visible absorption spectrum of the synthesized AgNP-K exhibited a broad peak at 447 nm. TEM, Zetasizer, and SEM-EDX results showed that the morphology and size of AgNP-K were nearly spherical in shape with 16.963 ± 6.0465 nm in size. XRD analysis confirmed that AgNP-K had a crystalline phase structure, while FTIR showed the absence of (-OH) group, indicating that kaempferol was successfully incorporated with silver. In DDA analysis, AgNP-K showed the largest inhibition zone (16.67 ± 1.19 mm) against MRSA as compared to kaempferol and commercial AgNPs. The MIC and MBC values for AgNP-K against MRSA were 1.25 and 2.50 mg/mL, respectively. The time-kill assay results showed that AgNP-K displayed bacteriostatic activity against MRSA. AgNP-K exhibited better antibacterial activity against MRSA when compared to commercial AgNPs or kaempferol alone.

Bacteriophage therapy for drug-resistant Staphylococcus aureus infections.

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.

Synthesis and characterization of marine seagrass (Cymodocea serrulata) mediated titanium dioxide nanoparticles for antibacterial, antibiofilm and antioxidant properties.

Cymodocea serrulata mediated titanium dioxide nanoparticles (TiO2 NPs) were successfully synthesized. The XRD pattern and FTIR spectra demonstrated the crystalline structure of TiO2 NPs and the presence of phenols, flavonoids and alkaloids in the extract. Further SEM revealed that TiO2 NPs has uniform structure and spherical in shape with their size ranged from 58 to 117 nm. Antibacterial activity of TiO2 NPs against methicillin-resistant Staphylococcus aureus (MRSA) and Vibrio cholerae (V. cholerae), provided the zone of inhibition of 33.9 ± 1.7 and 36.3 ± 1.9 mm, respectively at 100 µg/mL concentration. MIC of TiO2 NPs against MRSA and V. cholerae showed 84% and 87% inhibition at 180 µg/mL and 160 µg/mL respectively. Subsequently, the sub-MIC of V. cholerae demonstrated minimal or no impact on bacterial growth at concentration of 42.5 µg/mL concentration. In addition, TiO2 NPs exhibited their ability to inhibit the biofilm forming V. cholerae which caused distinct morphological and intercellular damages analysed using CLSM and TEM. The antioxidant properties of TiO2 NPs were demonstrated through TAA and DPPH assays and exposed its scavenging activity with IC50 value of 36.42 and 68.85 µg/mL which denotes its valuable antioxidant properties with potential health benefits. Importantly, the brine shrimp based lethality experiment yielded a low cytotoxic effect with 13% mortality at 100 µg/mL. In conclusion, the multifaceted attributes of C. serrulata mediated TiO2 NPs encompassed the antibacterial, antioxidant and anti-biofilm inhibition effects with low cytotoxicity in nature were highlighted in this study and proved the bioderived TiO2 NPs could be used as a promising agent for biomedical applications.

Mussel-inspired near-infrared light-responsive gelatin-based hydrogels for enhancing MRSA-infected wound healing.

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.

Biocompatible N-carbazoleacetic acid decorated CuxO nanoparticles as self-cascading platforms for synergistic single near-infrared triggered phototherapy treating microbial infections.

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.

Biomimetic ZrO2-modified seaweed residue with excellent fluorine/ bacteria removal and uranium extraction properties for wastewater purification.

Exploring and developing promising biomass composite membranes for the water purification and waste resource utilization is of great significance. The modification of biomass has always been a focus of research in its resource utilization. In this study, we successfully prepare a functional composite membrane, activated graphene oxide/seaweed residue-zirconium dioxide (GOSRZ), with fluoride removal, uranium extraction, and antibacterial activity by biomimetic mineralization of zirconium dioxide nanoparticles (ZrO2 NPs) on seaweed residue (SR) grafted with oxidized graphene (GO). The GOSRZ membrane exhibits highly efficient and specific adsorption of fluoride. For the fluoride concentrations in the range of 100-400 mg/L in water, the removal efficiency can reach over 99 %, even in the presence of interfering ions. Satisfactory extraction rates are also achieved for uranium by the GOSRZ membrane. Additionally, the antibacterial performance studies show that this composite membrane efficiently removes Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). The high adsorption of F- and U(VI) to the composite membrane is ascribed to the ionic exchange and coordination interactions, and its antibacterial activity is caused by the destruction of bacterial cell structure. The sustainability of the biomass composite membranes is further evaluated using the Sustainability Footprint method. This study provides a simple preparation method of biomass composite membrane, expands the water purification treatment technology, and offers valuable guidance for the resource utilization of seaweed waste and the removal of pollutants in wastewater.

Clinically Approved Ferric Maltol: A Potent Nanozyme with Added Effect for High-Efficient Catalytic Disinfection.

Nanozyme has been proven to be an attractive and promising candidate to alleviate the current pressing medical problems. However, the unknown clinical safety and limited function beyond the catalysis of the most reported nanozymes cannot promise an ideal therapeutic outcome in further clinical application. Herein, we find that ferric maltol (FM), a clinically approved iron supplement synthesized through a facile scalable method, exhibits excellent peroxidase-like activity than natural horseradish peroxidase-like (HRP) and commonly reported Fe-based nanozymes, and also shows high antibacterial performance for methicillin-resistant Staphylococcus aureus (MRSA) elimination (100%) and wound disinfection. In addition, with added effects inherited from contained maltol, FM can accelerate skin barrier recovery. Therefore, the exploration of FM as a safe and desired nanozyme provides a timely alternative to current antibiotic therapy against drug-resistant bacteria.

Hedscandines A-C, three undescribed indole alkaloids from Hedyotis scandens with their anti-MRSA activity.

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.

Combination antimicrobial therapy: in vitro synergistic effect of anti-staphylococcal drug oxacillin with antimicrobial peptide nisin against Staphylococcus epidermidis clinical isolates and Staphylococcus aureus biofilms.

The ability of Staphylococcus epidermidis and S. aureus to form strong biofilm on plastic devices makes them the major pathogens associated with device-related infections (DRIs). Biofilm-embedded bacteria are more resistant to antibiotics, making biofilm infections very difficult to effectively treat. Here, we evaluate the in vitro activities of anti-staphylococcal drug oxacillin and antimicrobial peptide nisin, alone and in combination, against methicillin-resistant S. epidermidis (MRSE) clinical isolates and the methicillin-resistant S. aureus ATCC 43,300. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) of oxacillin and nisin were determined using the microbroth dilution method. The anti-biofilm activities of oxacillin and nisin, alone or in combination, were evaluated. In addition, the effects of antimicrobial agents on the expression of icaA gene were examined by quantitative real-time PCR. MIC values for oxacillin and nisin ranged 4-8 µg/mL and 64-128 µg/mL, respectively. Oxacillin and nisin reduced biofilm biomass in all bacteria in a dose-dependent manner and this inhibitory effect was enhanced with combinatorial treatment. MBEC ranges for oxacillin and nisin were 2048-8192 µg/mL and 2048-4096 µg/mL, respectively. The addition of nisin significantly decreased the oxacillin MBECs from 8- to 32-fold in all bacteria. At the 1× MIC and 1/2× MIC, both oxacillin and nisin decreased significantly the expression of icaA gene in comparison with untreated control. When two antimicrobial agents were combined at 1/2× MIC concentration, the expression of icaA were significantly lower than when were used alone. Nisin/conventional oxacillin combination showed considerable anti-biofilm effects, including inhibition of biofilm formation, eradication of mature biofilm, and down-regulation of biofilm-related genes, proposing its applications for treating or preventing staphylococcal biofilm-associated infections, including device-related infections.