Multidrug-resistant Staphylococcus Aureus Research Articles

Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus

Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.

In silico Exploration of Essential Oil Constituents in Combating Multidrug-Resistant Staphylococcus aureus Infected Wounds

This research explores the multifaceted pharmacological actions of essential oils and its constituents, derived as secondary metabolites from aromatic plants, with a particular focus on their potent wound healing and antibacterial activities, elucidating their significance in therapeutic approach towards infected wounds. An in silico screening was carried out to identify the interaction between the bioactive essential oil contituents (EOC) such as cinnamaldehyde, citral, geraniol, linalool, and p-cymene, docked against various target proteins associated with antibiotic resistance and wound healing, including mec A (PDB ID- 4DK1), nor A (PDB ID- 7LO8), TGF- β1 (PDB ID- 1PY5), TGF- β2 (PDB ID- 1M9Z), VEGF (PDB ID-3QTK), GSK-3β (PDB ID-1Q5K) and MMP-9 (PDB ID-5UE4). The docking was done with AutoDock V 4.0 using five EOCs against seven receptors and the binding energy was gaged. The binding energy of EOCs were observed to be ranging from -5.3 kcal/mol to -2.55 kcal/mol. Notably, all the screened EOCs exhibited favourable binding affinity with GSK-3β, indicating their potential role in the inflammatory phase of wound healing. Additionally, towards antibiotic resistance, all EOC displayed adequate binding affinity with norA, suggesting their potential in modulating multidrug resistant efflux pumps. Compliance with Lipinski's rule, positions these EOC as promising candidates for drug development, particularly in the context of wound healing and antibiotic resistance. This study holds the promise of contributing novel insights to the field of wound care and combating antibiotic resistance, paving the way for innovative approaches in addressing the challenges posed by multi-drug resistant Staphylococcus aureus (MDRSA) infected wounds.

Antibiotic potentiating effect of Bauhinia purpurea L. against multidrug resistant Staphylococcus aureus.

Bauhinia purpurea L. is a medium-sized tree from the family Fabaceae. The plant is traditionally used as medicine by different tribes in Sikkim. The present study aimed to evaluate the modulation in minimum inhibitory concentration (MIC) of the bark methanol extract of Bauhinia purpurea L. against the clinical isolates of multidrug resistant Staphylococcus aureus. The synergistic activity of the test plant extract with different classes of antibiotics was also evaluated. The methanol extract of Bauhinia purpurea exhibited modulation by a 16-fold reduction in the MIC of clindamycin against both resistant and susceptible isolates, followed by penicillin and gentamicin, whereas a maximum of only a 4-fold MIC reduction was observed with ciprofloxacin. The lowest minimum inhibitory concentration and minimum bactericidal concentration showed by the plant extract was 0.48 and 0.97 mg/mL, respectively. The methanol extract of Bauhinia purpurea exhibited synergistic activity with penicillin, gentamicin, ciprofloxacin, and clindamycin against most of the tested isolates of multidrug-resistant Staphylococcus aureus (MDR-SA). Gas chromatography-mass spectrometry analysis of Bauhinia purpurea L. bark methanol extract revealed 16 phytocompounds. The results provide an insight into the potential antibacterial property of the plant extract in terms of its antibiotic MIC modulation and synergistic properties with the selected antibiotics. This is the first report of the antibiotic potentiation property of Bauhinia purpurea L., collected from Sikkim, India.

The functional small RNA interactome reveals targets for the vancomycin-responsive sRNA RsaOI in vancomycin-tolerant Staphylococcus aureus.

The emergence of multidrug-resistant Staphylococcus aureus (MRSA) is a major public health concern. Current treatment is dependent on the efficacy of last-line antibiotics like vancomycin. The most common cause of vancomycin treatment failure is strains with intermediate resistance or tolerance that arise through the acqusition of a diverse repertoire of point mutations. These strains have been shown to altered small RNA (sRNA) expression in response to antibiotic treatment. Here, we have used a technique termed RNase III-CLASH to capture sRNA interactions with their target mRNAs. To understand the function of these interactions, we have looked at RNA and protein abundance for mRNAs targeted by sRNAs. Messenger RNA and protein levels are generally well correlated and we use deviations from this correlation to infer post-transcriptional regulation and the function of individual sRNA-mRNA interactions. Using this approach we identify mRNA targets of the vancomycin-induced sRNA, RsaOI, that are repressed at the translational level. We find that RsaOI represses the cell wall autolysis Atl and carbon transporter HPr suggestion a link between vancomycin treatment and suppression of cell wall turnover and carbon metabolism.

Alkaloid rich hydroponic chili for AgNPs synthesis against multidrug resistant Staphylococcus aureus infected burn wounds

Hydroponic plant cultivation is expected to replace soil cultivation owing to an increased plant yield and rapid turnover. A number of medicinal plants have been successfully grown in hydroponic system. Effect of hydroponic cultivation on phytochemical content of medicinal plants needs to be investigated for efficient phytomedicine production. Herein, we quantify the bioactive compounds of medicinal importance in hydroponic and soil grown chili for green silver nanoparticles (AgNP) based formulation preparation. The end product has been evaluated as an alternate treatment for skin and soft tissue infections caused by Multidrug Resistant Staphylococcus aureus (MDRSA). Comparable phytochemical profile of soil grown chili extract (CESoil) and hydroponically grown chili extract (CEHydro) for increased production of plant sourced medicinally important compounds has been studied. Stable phytosynthesized CE NPs, confirmed by UV visible spectroscopy (UV) Fourier Transform Infrared (FTIR), Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM) analysis, showed enhanced anti-MDRSA activity in vitro with MIC and MBC at 0.312 and 0.625 mg/ml respectively. Hydrogel based CE NPs formulation successfully eliminated burn wound MDRSA infection in vivo while also regenerating the skin. Enhanced CE NPs activity in vitro and in vivo suggests their potential use in combating AMR infections that can further be evaluated in clinical trials.

Synthesis, characterization, radical scavenging properties of zinc oxide nanoparticles and inhibitory effect of ZnONPs-ciprofloxacin nanoconjugates on multidrug-resistant Staphylococcus aureus (MRSA) enzyme

The study determined the in vitro antioxidant potential of zinc oxide nanoparticles (ZnONPs) and inhibitory properties of ZnONPs-ciprofloxacin nanoconjugate on the activity of dehydrogenase enzyme from multi-drug resistant Staphylococcus aureus (MRSA). Rauwolfia vomitoria (SW) leaf extract was used for the synthesis of the ZnONPs. Volatile phytochemical constituents of the leaf extract were assessed using Gas Chromatography-Mass Spectrometry (GC–MS) which confirmed fifteen volatile phytochemicals with phytol (39.99 %) being the most abundant and the least being 4-hydoxy-3-methylacetophenone (0.85 %). The ZnONPs were characterized with UV–Vis spectroscopy, Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM), and Transmission Electrron Microscopy (TEM). The UV–Vis results showed maximum light absorption at a wavelength of 300 nm whereas EDS revealed 64.84 % Zn, 18.88 % O, and 16.28 % C. The microscopic studies gave agglomerated spherical zinc nanoparticles with average size of 99.02 nm. The free radical scavenging ability showed weaker properties for the ZnONPs compared to the control and the leaf extract. At 30 mg/mL, the nanoconjugates significantly (p < 0.05) recorded 100 % inhibition of the enzyme activities. The inhibitory properties of the antimicrobial agents indicated that ZnONPs-ciprofloxacin > ZnONPs > R. vomitoria leaf extract. The ZnONPs-ciprofloxacin nanoconjugate expressed mild dose–response inhibitory relationship (R2 = 0.66) against the MRSA dehydrogenase activity at the IC50 of 2.93 mg/mL.

Instant Protection Spray for Anti-Infection and Accelerated Healing of Empyrosis.

Distinct from common injuries, deep burns often require a chronic recovery cycle for healing and long-term antibiotic treatment to prevent infection. The rise of drug-resistant bacteria has caused antibiotics to no longer be perfect, and continuous drug use can easily lead to repeated infection and even death. Inspired by wild animals that chew plants to prevent wound infection, probiotic extracts with a structure similar to the tailspike of phage are obtained from Lactobacillus casei and combined with different flavones to design a series of nonantibiotic bactericides. These novel antibacterial agents are combined with a rapid gelation spray with a novel cross-angle layout to form an instant protection spray (IPS) and provide a physical and anti-infectious barrier for burns within 30 s. This IPS is able to sterilize 100.00% and 96.14% of multidrug-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, respectively. In addition, it is found to effectively reduce inflammation in MRSA-infected burns in rats and to promote tissue healing.

Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection

Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.

Synergistic action of endophytic fungi secondary metabolites against multidrug-resistant strains of Staphylococcus aureus

The global threat to treatment of infections associated with multidrug-resistant microorganisms as well as side effects associated with combination therapy calls for the urgent development of new medicines to address these challenges. Endophytic fungi are efficient bio synthesizers and offer a wide array of these reliable bioactive compounds. The present study is aimed at evaluating the effect of combined extracts of endophytic fungi isolated from the leaves of Musa paradisiaca against multidrug-resistant Staphylococcus aureus (MRSA) strains. Screening for multidrug resistance was carried out using the Kirby-Bauer disc diffusion assay followed by a preliminary assay of endophytic fungal extracts bioactivity using agar diffusion assay against selected MRSA. A synergistic study using checkerboard assay technique was performed, then extracts were subjected to quantitative evaluation of secondary metabolites using Gas Chromatography with Flame Ionization Detector. Axenic cultures of five endophytic fungi from M. paradisiaca (EMp1-Emp5) were isolated from the sampled leaves. All the endophytic fungal extracts inhibited the growth of all the multi-drug resistant Staphylococcus aureus at 0.5 mg/mL. Varying inhibition zones that were concentration-dependent were observed. The combined effects of EMp3 and EMp5 extracts at 9:1; 8:2; 4:6; 3:7; and 2:8 combination ratios produced synergistic effects against S. aureus (S18) with very low Fractional inhibitory Concentrations of 0.03:0.01, 0.01:0.01, 0.006:0.02, 0.01:0.04 and 0.01:0.1 mg/mL respectively. Several bioactive secondary metabolites such as anthocyanin, (-) epicatechin, naringenin, resveratrol, catechin, rutin, phenol were produced by the fungal endophytes. Our findings further affirm fungal endophytes associated with M. paradisiaca leaves as producers of natural antibacterial agents with synergistic potentials.

Analysis of the Responses to Pasteurization Temperatures of Methicillin Resistant Staphylococcus aureus Derived from Milk Items

Background and Aim: One of the leading causes of both community- and hospital-acquired infections is the superbug," multidrug-resistant Staphylococcus aureus (MRSA). Milk and dairy products seem to be highly vulnerable to a wide range of diseases. Therefore, we require processing procedures that both eliminate pathogens and lengthen the useful life of these products. The purpose of this study was to determine how susceptible MRSA isolates were to pasteurization temperatures after being recovered from dairy products.&#x0D; Materials and Methods: For the purpose of pasteurization, ten MRSA isolates were exposed to both a 63°C LTLT (low temperature, long time) therapy for 30 minutes and a 72°C HTST (high temperature, short time) treatment for 16 seconds.&#x0D; Results: The findings indicated that all isolates were killed by a pasteurization-like treatment at low temperature for a long time (63°C for 30 minutes), but that particular adaptable isolates could survive a pasteurization-like treatment at high temperature for a short time (72°C for 16 seconds), which may point to a time- and temperature-dependent variation in the thermal tolerance mechanism.&#x0D; Conclusion: The results showed that all isolates seemed extremely susceptible to damage from heat using LTLT pasteurization-like treatment (63°C for 30 minutes). Nevertheless, a particular number of these isolates succeeded in establishing colonies because they have quorum sensing structures that survive being handled by using heat damage at 72°C for 16 seconds. Pasteurized milk producers should be alerted to the fact that this microorganism has been found in contaminated milk since it compromises the product's safety and diminishes its value to consumers. As a result, it is strongly advised that manufacturers utilize varied temperatures for milk processing in order to remove the contaminating methicillin- and heat-resistant S. aureus (MHRSA).

Designing Alginate/Chitosan Nanoparticles Containing Echinacea angustifolia: A Novel Candidate For Combating Multidrug-resistant Staphylococcus aureus.

Nanoparticles (NPs) may help treat multidrug-resistant Staphylococcus aureus (MDR). This study prepared and evaluated chitosan/alginate-encapsulated Echinacea angustifolia extract against MDR strains. Evaluating synthesized NPs with SEM, DLS, and FTIR. Congo red agar and colorimetric plate techniques examined isolate biofilm formation. NP antibacterial power was assessed using well diffusion. Real-time PCR assessed biofilm-forming genes. MTT assessed the synthesized NPs' toxicity. According to DLS measurements, spherical E. angustifolia NPs had a diameter of 335.3 ± 1.43 nm. The PDI was 0.681, and the entrapment effectiveness (EE%) of the E. angustifolia extract reached 83.45 %. Synthesized NPs were most antimicrobial. S. aureus resistant to several treatments was 80 percent of 100 clinical samples. Biofilm production was linked to MDR in all strains. The ALG/CS-encapsulated extract had a 4 to 32-fold lower MIC than the free extract, which had no bactericidal action. They also significantly decreased the expression of genes involved in biofilm formation. E. angustifolia-encapsulated ALG/CS decreased IcaD, IcaA, and IcaC gene expression in all MDR strains (***p<0.001). Free extract, free NPs, and E. angustifolia-NPs had 57.5%, 85.5%, and 90.0% cell viability at 256 μg/ml. These discoveries could assist generate stable plant extracts by releasing natural-derived substances under controlled conditions.

Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment.

Long-term antibiotic use induces drug resistance in bacteria. This has given rise to the challenge of refractory infections, which have become a global health threat. Berberine (BBR) and tannic acid (TA) from plants exhibit promising antibacterial activities and may overcome antibiotic resistance. However, poor solubility and/or low penetration capability have limited their application. Carrier-free co-assembled nanocomposites composed entirely of BBR and TA exhibit improved or new properties and produce improved efficacy. Herein, we demonstrated that an ordered nanostructure could be spontaneously co-assembled by the solvent evaporation method using the two natural products. These co-assembled berberine-tannic acid nanoparticles (BBR-TA NPs) exhibited the best antibacterial effect compared with the corresponding physical mixture, pristine BBR, and some first-line antibiotics (benzylpenicillin potassium-BP and ciprofloxacin-Cip) against Staphylococcus aureus (S. aureus) and multidrug-resistant Staphylococcus aureus (MRSA). Even if the concentration of BBR-TA NPs was as low as 15.63 μg/mL, the antibacterial rate against S. aureus and MRSA was more than 80%. In addition to the synergistic effect of the two compounds, the antibacterial mechanism underlying the nanostructures was that they strongly adhered to the surface of the bacterial cell wall, thereby inducing cell membrane damage and intracellular ATP leakage. Furthermore, the in vivo wound healing effect of BBR-TA NPs was verified using an MRSA wound infection mouse model. The BBR-TA NPs achieved the best efficacy compared with BP and Cip. Moreover, cytotoxic and histopathological evaluations of mice revealed that the nanodrug had good biological safety. This facile and green co-assembly strategy for preparing nanoparticles provides a feasible reference for the clinical treatment of bacterial infection.

Prevalence, antimicrobial susceptibility pattern and multidrug resistance of methicillin-resistant Staphylococcus aureus isolated from clinical samples at a tertiary care teaching hospital: an observational, cross-sectional study from the Himalayan country, Nepal

ObjectiveWe sought to determine the prevalence and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the clinical samples at a tertiary care hospital in Nepal.MethodsCross-sectional, observational study design.Study...

Synergistic Interaction of Glycyrrhizin with Norfloxacin Displays ROS-Induced Bactericidal Activity against Multidrug-Resistant Staphylococcus aureus

Acquired bacterial resistance against several antibiotics has severely impaired the drug treatment regime. Multidrug-resistant Staphylococcus aureus (MDRSA) causes several life-threatening human pathologies. The introduction of novel antibiotics is a tedious process. Therefore, we have introduced glycyrrhizin (Gly) as a bioenhancer of norfloxacin (Nor), which showed synergistic interactions and a robust drug response. The drug resistance reversal potential of Gly against MDRSA was monitored. Gly and GlyNor (glycyrrhizin + norfloxacin) were used for spectrofluorometer and flow cytometry analysis for the measurement of free radicals and its effect upon cell membranes and macromolecules. Morphological analysis was carried out with the help of SEM. qRT-PCR analysis was conducted for gene regulation. Gly was observed to lower the MIC (minimum inhibitory concentration) of different groups of antibiotics up to 64-fold against MDRSA. GlyNor exerted oxidative stress, as evidenced by the measurement of reactive oxygen species (ROS) and their effect upon cell components. Gly and GlyNor showed membrane damage potential. The expression analysis of oxidative-related and MDR genes showed the up- and downregulation of these genes, respectively. GlyNor significantly lengthened post-antibiotic effects (PAE) and showed reduced mutation frequency rate (MFR). The synergistic bioenhancer properties of Gly with Nor and their enhanced ROS generation against MDRSA are reported for the first time in this study. Severe oxidative stress caused membrane damage, DNA fragmentation, transcriptional changes, and bacterial cell death. We strongly believe this could be a potential measure against rapidly evolving MDRSA.

Chemical profile and antibacterial activity of essential oil from ironwood (Eusideroxylon zwageri) sawdust

The current study describes for the first time the chemical compositions and antimicrobial activity of essential oils from ironwood sawdust (Eusideroxylon zwageri) obtained from Borneo Island. Fifteen terpene metabolites were identified by GC-MS of the ironwood sawdust essential oil extracted by steam distillation. (E)-β-Caryophyllene was the oil’s major compound (35.81 ± 0.25%), while its oxygenated derivative (caryophyllene oxide, 8.78 ± 0.08%) was the third biggest terpene. α-Copaene (13.05 ± 0.02%) was also observed in a significant amount together with other minor sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The oil also exhibited antibacterial activities against Gram-positive Multi-Drug Resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (strain ESBL) during a disc diffusion assay with inhibition zones of 6.13 ± 0.03 mm and 3.35 ± 0.05 mm, respectively.

Sulfonamide Porphyrins as Potent Photosensitizers against Multidrug-Resistant Staphylococcus aureus (MRSA): The Role of Co-Adjuvants.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 μM upon white light radiation with an irradiance of 25 mW cm-2 and a total light dose of 15 J cm-2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

Design and synthesis of novel anti-multidrug-resistant staphylococcus aureus derivatives of glycyrrhetinic acid by blocking arginine biosynthesis, metabolic and H2S biogenesis

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125–25 μM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 μM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 μM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.

Biomimetic Bacteriophage-Like Particles Formed from Probiotic Extracts and NO Donors for Eradicating Multidrug-Resistant Staphylococcus aureus.

Effectively clearing multidrug-resistant bacteria through nonantibiotic treatments is crucial for the recovery of infected tissues in favorable biological environments. Herein, a thermally responsive donor of cell-messenger nitric oxide (NO) is combined with extracts of food-grade Lactobacillus casei to form biomimetic phage-like microparticles with a tailspike structure. These particles can invade bacterial membranes and release NO to disrupt nitrogen and respiratory metabolisms, which initiates the programmed death of multidrug-resistant Staphylococcus aureus (MRSA) for inducing lysis, like the bacterial virus. Experiments suggest that these microparticles can also weaken bacterial toxicity and provide favorable conditions for cell proliferation because of the continuously released NO. By encapsulating these microparticles into graphene-oxide-doped polymers, a dual-mode antibacterial hydrogel (DMAH) can be constructed. In vivo results reveal that the DMAH achieves a long-time sterilization of MRSA with 99.84 ± 0.13% antibacterial rate in the dark because of the phage-like performance of the biomimetic microparticles. In its other antibacterial mode, DMAH subjected to 20min of near-infrared irradiation release NO, which, together with the photothermal effect, synergistically damages bacterial cell membranes to achieve very fast disinfection (97.13 ± 0.41% bactericidal rate). This multifunctional hydrogel can also significantly accelerate wound healing due to the phage-like particles.

Biogenic synthesis of CuO-NPs as nanotherapeutics approaches to overcome multidrug-resistant Staphylococcus aureus (MDRSA)

Due to the misuse of antibiotics, the multidrug-resistant Staphylococcus aureus (MDRSA) has caused serious infections and become more difficult to deal with. Here we propose to synthesise copper oxide nanoparticles (CuO-NPs) using a cell-free filter of Streptomyces rochei to enhance antibiotics activity against (MDRSA) and kill them. Characterisation of CuO-NPs using ultraviolet, dynamic light scattering, zeta potential, transmission electron microscopic (TEM), and X-ray diffraction, were investigated. The antibacterial action of the CuO-NPs was tested against standard strain and clinical isolates using the agar well diffusion method and the microdilution assay. The results showed the monodispersed spherical shape CuO-NPs with a mean diameter of 10.7 nm and were found to be active against (MDRSA). By a combination of CuO-NPs with different antibiotics, the highest synergistic effect was observed with cefoxitin, the minimum inhibitory concentration (MIC) was reduced to 6.5 for CuO-NPs, and 19.5 for cefoxitin. Time-kill assay showed the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h. The HFB-4 cells cultured in the presence of CuO-NPs showed normal morphology with 100% viability at 8 µg/ml. TEM showed that combination (1/4 MIC cefoxitin +1/16 MIC CuO-NPs) highly damages bacterial cells’ shape. The biosynthesis CuO-NPs showed antibacterial activity against S. aureus suggesting a promising alternative in clinical.

Injectable Carrier-Free Hydrogel Dressing with Anti-Multidrug-Resistant Staphylococcus aureus and Anti-Inflammatory Capabilities for Accelerated Wound Healing.

Antibacterial hydrogels have gradually become a powerful weapon to treat bacterially infected wounds and accelerate healing. In this paper, we designed a small-molecule self-healing antibacterial hydrogel containing 100% drug-loaded benzyl 3β-amino-11-oxo-olean-12-en-30-oate (GN-Bn), which was governed by π-π stacking, hydrogen bonding, and van der Waals forces. Due to the carrier-free design concept, the problems of interbatch variability during sample preparation and carrier-related toxicity can be effectively avoided. Moreover, the GN-Bn hydrogel exhibited promising antibacterial activities against multidrug-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of the GN-Bn hydrogel was 1.5625 nmol/mL, which was lower than those against clinical agents such as norfloxacin, penicillin, and tetracycline. This is attributed to its unique antibacterial mechanism that aims at killing bacteria or preventing their growth by regulating arginine biosynthesis and metabolism through both transcriptomic (RNA-seq) analysis and quantitative polymerase chain reaction (qPCR) analysis. In addition, the GN-Bn hydrogel can also inhibit proinflammatory cytokines (TNF-α, IL-1β, and IL-6) to promote wound healing. Collectively, the GN-Bn hydrogel elicited dual therapeutic effects on an MRSA-infected full-thickness skin wound model through its antibacterial and anti-inflammatory activities, which is attributed to the fact that the GN-Bn hydrogel has multiple advantages including sufficient mechanical stability, biocompatibility, and unique antibacterial mechanisms, making it significantly accelerate MRSA-infected full-thickness skin wound healing as a wound dressing. In a word, the GN-Bn antibacterial hydrogel dressing with an anti-inflammatory and antibacterial bifunctional material holds great potential in clinical application.