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Both bacteria-infection and excessive inflammation delay the wound healing process and even create non-healing wound, thus it is highly desirable to endow the wound dressing with bactericidal and anti-oxidation properties. Herein an antibacterial and antioxidation hydrogel based on Carbomer 940 (CBM) and hydroxypropyl methyl cellulose (HPMC) loaded with tea polyphenols (TP) and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The hydrogel killed 99.9 % of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at 10 7  CFU mL -1 , and showed strong antioxidation against H 2 O 2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) radicals without noticeable cytotoxicity in vitro. The CBM/HPMC/HBPL/TP hydrogel significantly shortened the inflammatory period of the MRSA-infected full-thickness skin wound of rats in vivo, with 2 orders of lower MRSA colonies compared with the blank control, and promoted the wound closure especially at the earlier stage. The inflammation was suppressed and the vascularization was promoted significantly as well, resulting in reduced pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-10 (IL-10)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

This research work reports the time evolution of the electrical properties of gram-positive and gram-negative bacteria in aqueous suspensions with methyl violet and Lugol; measurements of galvanostatic electrical impedance spectra were made in a frequency range of 10Hz to 100kHz. The magnitude of the impedance as a function of frequency for methicillin-resistant strains, Staphylococcus aureus (gram-positive), and Escherichia coli O157: H7 (gram-negative) in the presence of methyl violet and Lugol, showed that both strains exhibited a progressive decrease in the magnitude of the electrical impedance with an increasing bacterial population; however, the variation in the magnitude rate of the impedance over time is completely different between the gram-positive and gram-negative strains. The results suggest that the time evolution of the electrical impedance spectra can be used to differentiate Staphylococcus aureus from Escherichia coli bacteria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Herein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (MBEC) and minimum biofilm inhibition concentration (MBIC) assays. The compounds displayed antibiofilm properties and represent intriguing scaffolds for further optimization and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Three undescribed (1-3) and nine known (4-12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 μg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 μg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (K D  = 1.72 μM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thiomersal (TM) is an excellent preservative that is used in a wide variety of products, like pharmaceuticals, cosmetics, and vaccines, etc. Its usage has been in decline because of safety concerns. Since vaccine production is on the rise, its use may increase further in low-income and developing countries, as a cost-effective vaccine preservative. Further, Thiomersal is still being used as an essential component in various pharmaceutical preparations. In this light, the present study addresses its mechanism of toxicity in zebrafish and unveils a novel strategy for lessening its negative effects by conjugating cysteine to it, while retaining its antibacterial efficacy. We show that the mitochondrial membrane potential is destabilised by TM, leading to the induction of apoptosis. Interestingly, TM-cysteine conjugate (at a ratio of 1:1) showed no toxicity in zebrafish, whereas TM alone was highly toxic. Importantly, assaying for the bactericidal activity, tested using Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA), revealed that the conjugate retains the antibacterial activity, demonstrating that the TM-cysteine conjugate is a safer alternative to TM as a vaccine preservative, and in all the other products that still use TM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Nanoparticle (NP) conjugation with various biomolecules is one of the most promising approaches for targeting Methicillin-resistant Staphylococcus aureus (MRSA). In this study, berberine (BER) was conjugated with gold nanoparticles (AuNPs) to enhance its antibacterial activity against MRSA. Chemically synthesized AuNPs were characterized by UV-vis spectroscopy, size distribution and Field Emission-Scanning Electron Microscope (FE-SEM) analysis. Berberine was conjugated with AuNPs and the conjugants were characterized using UV-vis spectroscopy and Fourier Transform Infrared (FTIR). The cytotoxicity of free and conjugated BER was also investigated. Comparative studies were conducted based on the Minimum Inhibitory Concentration (MIC) and anti-biofilm activities of conjugants and free BER against MRSA isolates. To verify cell membrane disruption and intracellular imbalance following treatment exposure, reactive oxygen species (ROS) and live-dead staining experiments were performed. In vivo antibacterial efficacy of treated groups was also assessed in a BALB/c mouse-infected skin model. DLS measurement, FE-SEM, and UV-vis spectroscopy confirmed the synthesis of AuNPs with a narrow size distribution of 49.38 nm and a zeta potential of -31.9 mV. The results from UV-vis spectroscopy and FTIR provided support for the functionalization of AuNPs by BER functional groups. The In vitro antibacterial results demonstrated that the conjugated BER exhibited a lower MIC value against MRSA (109.5 μg/ml) compared to free BER (165 μg/ml). Free and conjugated BER, at their MIC concentrations, demonstrated anti-biofilm activity, resulting in biofilm eradication of 13.9 and 22.33 %, respectively. The highest level of ROS production (93 %) was associated with the conjugated BER at a concentration of 27.37 μg/ml. This finding indicates a disruption in cell membrane integrity and a reduction in bacterial viability, as demonstrated by ROS and live/dead staining assays. The cytotoxicity study on the mouse L929 fibroblast cell line revealed approximately 100 % cell viability when exposed to free or conjugated BER at their MIC concentration. This result indicates the biosafety of both of the compounds. The in vivo study in the infected skin model groups treated with conjugated and free BER revealed MRSA survival rate of 2.7 % and 26 %, respectively. These findings suggest that conjugated BER could be an effective nanoformulation candidate with a potential role in managing MRSA associated infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ceftobiprole (CBP) is an anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin with a wide spectrum of activity. We aimed to describe our experience of real-life use of CBP for the treatment of severe infections of critically ill patients with multiple infected sites and related trough CBP concentrations. We performed a retrospective, observational, monocentric study in our intensive care unit (ICU) that included all patients treated with CBP for documented infections between January 2016 and December 2021. We collected demographic, clinical, and microbiological data. When available, we report the CBP trough concentrations. The primary endpoint was clinical cure at the end of treatment. The secondary endpoints were in-hospital mortality and documentation of the carriage of multidrug-resistant (MDR) bacteria not present before CBP treatment. Between January 2016 and December 2021, 47 patients were treated in the ICU with CBP. The main indication for treatment was pneumonia (51%) and most patients presented with associated bacteremia (72%). All infections were polymicrobial. A clinical cure was achieved for nearly 80% of the patients. Only five patients presented new carriage of MDR bacteria. In-hospital mortality was 32%. Out of 21 strains of Enterobacterales for which the MIC was available, 33% were considered to be resistant to CBP according to the EUCAST 2023 clinical breakpoint. Trough CBP concentrations were reported for 16 patients. In our real-life experience, treatment of ICU patients with CBP for polymicrobial severe infections resulted in most cases in a clinical cure. Monitoring of trough concentrations is critical, especially in cases of high MIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The current study was conducted to evaluate the effectiveness of geraniol nanophytosomes in accelerating the healing process of wounds infected with Methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model. The physicochemical properties confirmed physical properties and successful synthesis of the nanophytosomes. Wounds were induced and mice (n = 90) were treated with a base ointment (negative control group) and/or mupirocin (positive control) and also formulations prepared from geraniol (GNL), geraniol nanophytosomes (NPhs-GNL), and PVA/NPhs-GNL. Wound contraction, total bacterial count, pathological parameters and the expressions of bFGF, CD31 and COL1A were also assessed. The results showed that topical administration of mupirocin and PVA/NPhs/GNL increased wound contraction, fibroblast and epithelization and also the expressions of bFGF, CD31 and COL1A while decreased the expression of total bacterial count and edema compared with negative control mice (P = 0.001). The results also showed that PVA/NPhs-GNL and mupirocin could compete and PVA/NPhs-GNL formulation was safe. In conclusion, the prepared formulations accelerated the wound healing process by modulation in proliferative genes. Geraniol nanophytosomes loaded into PVA could improve the healing in infected full-thickness wounds healing process and can be used for the treatment of infected wounds after future clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Sonodynamic inactivation (SDI) of pathogens has an important advantage when compared to optical excitation-based protocols due to the deeper penetration of ultrasound (US) excitation in biological media or animal tissue. Sonosensitizers (SS) are compounds or systems that upon US stimulation in the therapeutic window (frequency = 0.8-3 MHz and intensity < 3 W/cm 2 ) can induce damage to vital components of pathogenic microorganisms. Herein, we report the synthesis and application of conjugated polymer nanoparticles (CPNs) as an efficient SS in SDI of methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Candida tropicalis. A frequent problem in the design and testing of new SS for SDI is the lack of proper sonoreactor characterization which leads to reproducibility concerns. To address this issue, we performed dosimetry experiments in our setup. This enables the validation of our results by other researchers and facilitates meaningful comparisons with different SDI systems in future studies. On a different note, it is generally accepted that the mechanisms of action underlying SS-mediated SDI involve the production of reactive oxygen species (ROS). In an attempt to establish the nature of the cytotoxic species involved in our CPNs-based SDI protocol, we demonstrated that singlet oxygen ( 1 O 2 ) does not play a major role in the observed sonoinduced killing effect. SDI experiments in planktonic cultures of optimally growing pathogens using CPNs result in a germicide effect on the studied pathogenic microorganisms. The implementation of SDI protocols using CPNs was further tested in mature biofilms of a MRSA resulting in ∼40 % reduction of biomass and ∼70 % reduction of cellular viability. Overall, these results highlight the unique and unexplored capacity of CPNs to act as sonosensitizers opening new possibilities in the design and application of novel inactivation protocols against morbific microbes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The rapid spread of Methicillin-resistant Staphylococcus aureus (MRSA) and its difficult-to-treat skin and filmsy diseases are making MRSA a threat to human life. The most dangerous feature is the fast emergence of MRSA resistance to all recognized antibiotics, including vancomycin. The creation of novel, effective, and non-toxic drug candidates to combat MRSA isolates is urgently required. Fluorine containing small molecules have taken a centre stage in the field of drug development. Over the last 50 years, there have been a growing number of fluorinated compounds that have been approved since the clinical usage of fluorinated corticosteroids in the 1950 s and fluoroquinolones in the 1980 s. Due to its advantages in terms of potency and ADME (absorption, distribution, metabolism, and excretion), fluoro-pharmaceuticals have been regarded as a potent and useful tool in the rational drug design method. The flexible bioactive fluorinated azoles are ideal candidates for the development of new antibiotics. This review summarizes the decade developments of fluorinated azole derivatives with a wide antibacterial activity against diverged MRSA strains. In specific, we correlated the efficacy of structurally varied fluorinated azole analogues including thiazole, benzimidazole, oxadiazole and pyrazole against MRSA and discussed different angles of structure-activity relationship (SAR)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale: Respiratory culture screening is mandatory for all potential lung transplant donors. There is limited evidence on the significance of donor multidrug-resistant (MDR) bacteria on transplant outcomes. Establishing the safety of allografts colonized with MDR bacteria has implications for widening an already limited donor pool., Objectives: We aimed to describe the prevalence of respiratory MDR bacteria among our donor population and to test for associations with posttransplant outcomes., Methods: This retrospective observational study included all adult patients who underwent lung-only transplantation for the first time at King Faisal Specialist Hospital & Research Centre in Riyadh from January 2015 through May 2022. The study evaluated donor bronchoalveolar lavage and bronchial swab cultures., Main Results: Sixty-seven of 181 donors (37%) had respiratory MDR bacteria, most commonly MDR Acinetobacter baumannii (n = 24), methicillin-resistant Staphylococcus aureus (n = 18), MDR Klebsiella pneumoniae (n = 8), MDR Pseudomonas aeruginosa (n = 7), and Stenotrophomonas maltophilia (n = 6). Donor respiratory MDR bacteria were not significantly associated with allograft survival or chronic lung allograft dysfunction (CLAD) in adjusted hazard models. Sensitivity analyses revealed an increased risk for 90-day mortality among recipients of allografts with MDR Klebsiella pneumoniae (n = 6 with strains resistant to a carbapenem and n = 2 resistant to a third-generation cephalosporin only) compared to those receiving culture-negative allografts (25.0% versus 11.1%, p = 0.04). MDR Klebsiella pneumoniae (aHR 3.31, 95%CI 0.95-11.56) and Stenotrophomonas maltophilia (aHR 5.35, 95%CI 1.26-22.77) were associated with an increased risk for CLAD compared to negative cultures., Conclusion: Our data suggest the potential safety of using lung allografts with MDR bacteria in the setting of appropriate prophylaxis; however, caution should be exercised in the case of MDR Klebsiella pneumoniae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This paper aimed to evaluate the effects of the COVID-19 pandemic on prescription rates and antibiotic resistance in a university hospital. A retrospective study was conducted on the medical records of patients admitted to the Bihor Emergency Clinical County Hospital in Romania in 2019 (pre-pandemic) and 2021 (during the pandemic period). We evaluated the antibiotic consumption index (ACI) and susceptibility rates. The overall percentage of antibiotic prescribing increased in 2021, while the total number of patients decreased. Genito-urinary, digestive, respiratory infections, heart diseases and wounds were the most common conditions for antibiotic prescriptions, but the number of them decreased in 2021. There was a decrease in the proportion of antibiotics from the Watch and Reserve class and an increase in the proportion of antibiotics from the Access class. Antibiotic use has been reduced despite an increase in the number of patients, with a high consumption in the Watch group in the ICU wards. By contrast, surgical wards had the highest rate of antibiotic prescriptions, but a decrease in the number of patients. The patients who were administered antibiotics were hospitalized for diagnoses other than COVID-19. Almost all prescribed antibiotics displayed decreasing sensitivity rates. The number of isolated ESKAPE pathogens, except for Staphylococcus aureus methicillin-resistant strains, were increased. Strategies to control antibiotic prescriptions and the spread of resistant pathogens should be improved. [ABSTRACT FROM AUTHOR]

Objective: A growing number of studies have demonstrated the antimicrobial activity of natural products against multidrug-resistant bacteria. This study aimed to apply scientometric method to explore the current status and future trends in this field. Methods: All relevant original articles and reviews for the period 1997-2021 were retrieved from the Web of Science Core Collection database. VOSviewer, a scientometric software, and an online bibliometric analysis platform were used to conduct visualization study. Results: A total of 1,267 papers were included, including 1,005 original articles and 262 reviews. The United States and India made the largest contribution in this field. The University of Dschang from Cameroon produced the most publications. Coutinho HDM, Kuete V, and Gibbons S were key researchers, as they published a great many articles and were co-cited in numerous publications. Frontiers in Microbiology and Antimicrobial Agents and Chemotherapy were the most influential journals with the highest number of publications and co-citations, respectively. "Medicinal plants", "methicillin-resistant Staphylococcus aureus", "biofilm", "minimum inhibitory concentration", and "efflux pumps" were the most frequently used keywords, so these terms are presumed to be the current hot topics. All the included keywords could be roughly divided into four major themes, of which the theme of "natural product development approach" had attracted much attention in recent years. Furthermore, "Pseudomonas aeruginosa", "nanoparticles", "green synthesis", "antimicrobial peptides", "antibiofilm", "biosynthetic gene clusters", and "molecular dynamics simulation" had the latest average appearance year, indicating that these topics may become the research hot spots in the coming years. Conclusion: This study performed a scientometric analysis of the antibacterial activity of natural products against multidrug-resistant bacteria from a holistic perspective. It is hoped to provide novel and useful data for scientific research, and help researchers to explore this field more intuitively and effectively. [ABSTRACT FROM AUTHOR]

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Ethnopharmacological Relevance: Atractylodis Rhizoma is extensively employed in Traditional Chinese Medicine for the treatment of skin and gastrointestinal ailments. Its active components have been proven to demonstrate numerous beneficial properties, including antibacterial, antiviral, anti-inflammatory, anti-tumor, and anti-ulcer activities. Furthermore, the volatile oil from Atractylodis Rhizoma (VOAR) has been reported to effectively inhibit and eradicate pathogens such as Staphylococcus aureus, Escherichia coli and Candida albicans. Of particular concern is Staphylococcus pseudintermedius, the predominant pathogen responsible for canine pyoderma, whose increasing antimicrobial resistance poses a serious public health threat. VOAR merits further investigation regarding its antibacterial potential against Staphylococcus pseudintermedius., Aim of the Study: The study aims to verify the in vitro antibacterial activity of VOAR against Staphylococcus pseudintermedius. And a superficial skin infection model in mice was established to assess the in vivo therapeutic effect of VOAR., Materials and Methods: Thirty strains of S. pseudintermedius were isolated from dogs with pyoderma, and the drug resistance was analyzed by disc diffusion method. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of VOAR were determined through the broth dilution method. The growth curve of bacteria in a culture medium containing VOAR was monitored using a UV spectrophotometer. Scanning electron microscopy was employed to observe the effects of VOAR on the microstructure of S. pseudintermedius. The impact of VOAR on the antibiotic resistance of S. pseudintermedius was assessed using the disc diffusion method. Twenty mice were randomly divided into four groups: the control group, the physiological saline group, the VOAR group, and the amikacin group. With the exception of the control group, the skin barrier of mice was disrupted by tap stripping, and the mice were subsequently inoculated with S. pseudintermedius to establish a superficial skin infection model. The modeled mice were treated with normal saline, VOAR, and amikacin for 5 days. Following the treatment period, the therapeutic effect of each group was evaluated based on the measures of body weight, skin symptoms, tissue bacterial load, tissue IL-6 content, and histopathological changes., Results: The MIC and MBC of VOAR against 30 clinical isolates of S. pseudintermedius were found to be 0.005425% and 0.016875%, respectively. VOAR could exhibit the ability to delay the entry of bacteria into the logarithmic growth phase, disrupt the bacterial structure, and enhance the antibacterial zone in conjunction with antibiotic drugs. In the superficial skin infection model mice, VOAR significantly reduced the scores for skin redness (P < 0.0001), scab formation (P < 0.0001), and wrinkles (P < 0.0001). Moreover, VOAR markedly reduced the bacterial load (P < 0.001) and IL-6 content (P < 0.0001) in the skin tissues of mice. Histopathological observations revealed that the full-layer skin structure in the VOAR group was more complete, with clearer skin layers, and showed significant improvement in inflammatory cell infiltration and fibroblast proliferation compared to other groups., Conclusion: The results demonstrate that VOAR effectively inhibits and eradicates Staphylococcus pseudintermedius in vitro while also enhancing the pathogen's sensitivity to antibiotics. Moreover, VOAR exhibits a pronounced therapeutic effect in the superficial skin infection model mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Erythrodermic psoriasis (EP) is a severe and rare condition characterized by prominent erythema and scaling over 75 % of the body surface area. Unlike psoriasis vulgaris (PV), EP carries high risk of systemic involvement, including superficial skin infections and sepsis, particularly those caused by Staphylococcus aureus., Objective: To explore the microecological characteristics of EP and detect the levels of antimicrobial peptides (AMPs) in both skin and serum of EP patients., Methods: In this study, skin microbiomes of 10 EP patients were analyzed through 16S rRNA gene sequencing. The expressions of AMPs, Interleukin-4/13 (IL-4/13), Interleukin-17 (IL-17) and Interferon-γ (IFN-γ) in skin were detected via immunohistochemical staining and serum levels of AMP were evaluated by ELISA. We also enrolled 10 AD and 10 PV patients as controls., Results: EP patients retained rich microbial diversity, dominated by S. aureus. The AMPs of hBD2, LL-37, and RNase7 in EP keratinocytes were significantly lower than those in PV, but higher than those in AD. The expression levels of IL-4, IL-13 and IFN-γ in lesions are similar between EP and AD, but quite different from PV. What's more, the serum AMP levels in EP were similar to those in PV while significantly lower than in AD., Conclusion: We found EP patients have a rich microbial diversity dominated by S. aureus in lesions, while lower serum and skin AMPs expressions, which may account for the increased incidence of S. aureus cutaneous infections and sepsis in EP patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Infections caused by drug-resistant bacteria have become a new challenge in infection treatment, gravely endangering public health. Chloramphenicol (CL) is a well-known antibiotic which has lost its efficacy due to bacterial resistance. To address this issue, herein we report the design, synthesis and biological evaluations of novel triphenylphosphonium chloramphenicol conjugates (TPP + -CL). Study results indicated that compounds 39 and 42 possessed remarkable antibacterial effects against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 2 μg/mL, while CL was inactive to the tested MRSA strains. In addition, these conjugates exhibited rapid bactericidal properties and low toxicity, and did not readily induced bacterial resistance, obviously outperforming the parent drug CL. In a mouse model infected with a clinically isolated MRSA strain, compound 39 at a dose of 20 mg/kg exhibited a comparable or even better in vivo anti-MRSA efficacy than the golden standard drug vancomycin, while no toxicity was observed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The emergence and increasing prevalence of multidrug-resistant (MDR) bacteria have posed an urgent demand for novel antibacterial drugs. Currently, antimicrobial peptides (AMPs), potential novel antimicrobial agents with rare antimicrobial resistance, represent an available strategy to combat MDR bacterial infections but suffer the limitation of protease degradation. In this study, we developed a highly effective method for optimizing the stability of AMPs by introducing fluorinated sulfono-γ-AApeptides, and successfully synthesized novel Feleucin-K3-analogs. The results demonstrated that the incorporation of fluorinated sulfono-γ-AA into Feleucin-K3 effectively improved stability and afforded optimal peptides, such as CF 3 -K11, which exhibited 8-9 times longer half-lives than Feleucin-K3. Moreover, CF 3 -K11 displayed potent antimicrobial activity against clinically isolated Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), excellent biosafety, low resistance propensity, and possessed powerful antimicrobial efficacy for both local skin infection and pneumonia infection. The optimal CF 3 -K11 exhibited strong therapeutic potential and offered a superior approach for treating MDR bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and -25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. STATEMENT OF SIGNIFICANCE: Bacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Vancomycin is a widely used antibiotic for the treatment of gram-positive bacterial infections, especially for methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to a small therapeutic range and large inter-patient variability, therapeutic drug monitoring (TDM) of vancomycin is required to minimize toxicity and maximize treatment efficacy. Venous blood sampling is mostly applied for TDM of vancomycin, although this widely used sampling method is more invasive compared to less painful alternatives, such as the dried blood spot (DBS) method, which can be performed at home., Method: We developed an UPLC-MS/MS method for the quantification of vancomycin and creatinine in DBS. A fast sample preparation and short analysis run time of 5.2 min were applied, which makes this method highly suitable for clinical settings. Validation was performed according to international (FDA and EMA) guidelines., Results: The validated concentration range was found linear for creatinine from 41.8 µmol/L to 722 µmol/L and for vancomycin from 3.8 mg/L to 76.6 mg/L (r 2  > 0.990) and the inaccuracies, imprecisions, hematocrit effects, and recoveries were < 15 % for both compounds. No significant carryover effect was observed., Conclusion: Hence, we successfully validated a quantification method for the simultaneous determination of creatinine and vancomycin in DBS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Carex baccans, known as Shan-Bai-Zi or Ye-Gao-Liang in China, is a traditional medicinal herb used by several ethnic groups in Yunnan Province. It is utilized for the treatment of wound infections, ulcers, and dysentery. However, there is currently a dearth of research reports on its antimicrobial potential., Aim of the Study: The substance basis of the antimicrobial activity of C. baccans will be unveiled, and the in vitro and in vivo antibacterial activities against multidrug-resistant bacteria of its major active compounds, as well as their preliminary mechanisms of action, will be investigated., Materials and Methods: An antibacterial bioactivity-guided isolation method was used to isolate and identify the active compound curcusinol from C. baccans. UPLC-DAD-MS was employed for the quantitative analysis of curcusinol. The antibacterial activity, resistance profile, synergistic effects, anti-biofilm activity, and potential mechanisms of action of curcusinol against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and other multidrug-resistant bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii) were investigated using various methods, including the broth microdilution method, scanning electron microscopy, time kill assay, multi-generational resistance induction assay, checkerboard synergy assay, anti-biofilm assay, and metabolomics. Furthermore, the therapeutic efficacy of curcusinol was assessed in vivo by establishing an animal skin wound infection model of MRSA., Results: Curcusinol was isolated from the fruit of C. baccans, which accounts for 3.1% of the dry weight of the fruit. Curcusinol exhibited significant bactericidal and anti-biofilm activities against antibiotic-resistant Gram-positive bacteria in vitro. Furthermore, curcusinol acted as an antibiotic adjuvant to enhance the activity of various commonly used antibiotics against both Gram-positive and Gram-negative antibiotic-resistant bacteria without cytotoxicity to mammalian cells (A549 and RAW264.7) at 64 μM. Moreover, curcusinol affected arginine biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism significantly in MRSA cells under stress. Additionally, curcusinol effectively treated MRSA-infected mouse skin wounds and accelerated wound healing in vivo., Conclusions: The results of this study not only support the traditional uses of C. baccans but also demonstrate that its major active compound, curcusinol, is an effective plant-derived bactericidal agent and antibacterial adjuvant with potential applications in the treatment of skin infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bacterial infections typically invade the living tissue of wounds, thereby aggravating the inflammatory response, delaying wound healing, or causing further complications. In this paper, the antibacterial hydrogel (PNVBA) with antifreezing and antidrying properties was prepared by a two-step method using N -isopropylacrylamide (NIPAM), 1-butyl-3-vinylimidazolium bromide (VBIMBr), and 3-acrylamidophenylboronic acid (AAPBA). PNVBA hydrogels exhibited a high adsorption capacity of 280 mg·g -1 for bovine serum albumin (BSA) and can adhere to the surface of different materials through ion-dipole or hydrogen-bonding interactions. Meanwhile, the PNVBA hydrogels exhibited high viscoelasticity and good adhesion after freezing at -20 °C or heating at 70 °C for 24 h with a sterilizing rate of up to 98% against multidrug-resistant (MDR) Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, a survival rate of up to 90% after incubation with L929 cells over 24 h was observed. Therefore, this inherent antibacterial hydrogel can be used as an excellent alternative material for wound dressings.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents. Inspired by our recent report on the antibacterial activity of etrasimod, an immunomodulating drug candidate, we prepared a series of etrasimod derivatives by varying substituents on the phenyl ring, altering the central tricyclic aromatic ring, and modifying the carboxyl group. From this series of compounds, indole derivative 24f was identified as the most potent antibacterial compound, with the minimum inhibitory concentration (MIC) values between 2.5 and 10 μM against various Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), S. epidermidis and enterococci. Moreover, 24f exhibited rapid bactericidal activity against S. aureus, low toxicity and hemolytic activity, and a synergistic effect with gentamicin against S. aureus, MRSA, and Enterococcus faecalis. Furthermore, it was shown that neither etrasimod nor 24f affects S. aureus cell membranes. Importantly, 24f did not induce resistance in S. aureus, representing a significant improvement compared to etrasimod. Finally, the antibacterial activity of etrasimod and 24f against S. aureus and MRSA was confirmed in vivo in a Caenorhabditis elegans infection model. Taken together, our study highlights the value of etrasimod and its derivatives as potential antibacterial candidates for combating infections caused by Gram-positive bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The characteristics of biofilms have exacerbated the issue of clinical antibiotic resistance, rendering it a pressing challenge in need of resolution. The combination of biofilm-dispersing agents and antibiotics can eliminate biofilms and promote healing synergistically in infected wounds. In this study, we developed a novel nanocomposite hydrogel (NC gel) comprised of the poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG) based bioadhesive nanoparticles (BNPs) and a hydrophilic carboxymethyl chitosan (CS) network. The NC gel was designed to co-deliver two biofilm-dispersing agents (an NO-donor SNO, and an α-amylase Am) and an antibiotic, cefepime (Cef), utilizing a synergistic anti-biofilm mechanism in which Am loosens the matrix structure and NO promotes the release of biofilm bacteria via quorum sensing, and Cef kills bacteria. The drug-loaded NC gel (SNO/BNP/CS@Am-Cef) demonstrated sustained drug release, minimal cytotoxicity, and increased drug-bacterial interactions at the site of infection. When applied to mice infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vivo, SNO/BNP/CS@Am-Cef enhanced biofilm elimination and promoted wound healing compared to traditional antibiotic treatments. Our work demonstrates the feasibility of the co-delivery of biofilm-dispersing agents and antibiotics using the NC gel and presents a promising approach for the polytherapy of bacterial biofilm-related infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Mec A, as a representative gene mediating resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA), allows a new genetic analysis for the detection of MRSA. Here, a sensitive, prompt, and visual colorimetry is reported to detect the Mec A gene based on toehold-mediated strand displacement (TMSD) and the enrichment effect of graphene oxide (GO). The Mec A triggers to generate the profuse amount of signal units of single-stranded DNA (SG) composed of a long single-stranded base tail and a base head: the tail can be adsorbed and enriched on the surface of GO; the head can form a G quadruplex structure to exert catalytic function towards 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid). Therefore, through the enrichment effect of GO, the signal units SG reflects different degrees of signal amplification on different substrates (such as aqueous solution or filter membrane). This strategy demonstrates a broad linear working range from 100 pM to 1.5 nM (solution) and 1 pM to 1 nM (filter membrane), with a low detection limit of 39.53 pM (solution) and 333 fM (filter membrane). Analytical performance in real samples suggests that this developed colorimetry is endowed with immense potential for clinical detection applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Staphylococcus aureus (S. aureus) as a major pathogen is implicated in a wide range of foodborne and hospital-acquired infections, its methicillin resistant variants contribute to the spread of β-lactam antibiotic resistance. It is essentially important to destroy these pathogens, their resistance genes and the antibiotics in wastewaters. For this purpose reactions of reactive radicals (advanced oxidation processes), first of all hydroxyl radicals ( • OH), are suggested. Here the radiolysis of water supplied these radicals. In the experiments B.01755 oxacillin sensitive and B.02174 resistant S. aureus strains were used to study their behaviorr in suspensions under the effect of irradiation in presence and absence of oxacillin. Oxacillin inactivation depended on concentration of the antibiotic used (0.042 and 1 g dm -3 ), higher concentration required a higher dose. When 10 6 -10 9  CFU cm -3  S. aureus suspensions were irradiated with γ-radiation the bacteria were inactivated at low absorbed doses: 4 orders of magnitude decrease ocurred in the number of culturable cells at ∼0.6 kGy dose. Both cell membrane and DNA suffered considerable damages during irradiation. Due to the membrane damage the cells could not be stained, and the DNA content of cells in several days period was released into the solution. In DNA damage the oxacillin resistance mecA gene was also modified, it did not multiply in PCR test. These findings are important from the point of view of applying irradiation technology to stop the spread of antibiotic resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1 H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The expeditious healing of chronic wounds with bacterial infections poses a formidable challenge in clinical practice because of the persistent bacterial presence, excessive inflammation, and the accumulation of reactive oxygen species (ROS) in clinical practice. Thus, in this study, natural antimicrobial material microneedles (MNs) with multifunctional properties were prepared by adding peony leaf extract (PLE) into a matrix of methacrylated Bletilla striata polysaccharide (BSPMA) and methacrylated chitosan (CSMA) via cross-linking under ultra-violet light to accelerate the rapid healing of chronic wounds with bacterial infections. Results showed that BCP-MNs effectively inhibited the growth of Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) by disrupting bacterial cell membranes and accelerated the healing of infected wounds by enhancing cell migration, epidermal regeneration, pro-collagen deposition, and angiogenesis and reducing inflammation. Furthermore, BCP-MNs not only possessed good mechanical properties, stability, and biocompatibility but also showed potent antioxidant effects to eliminate excessive ROS accumulation in the wound bed. In conclusion, BCP-MNs possess multifunctional wound-healing properties and can serve as excellent wound dressing in to treat infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities., Method: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached., Results: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia., Conclusions: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

It is unclear whether anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs should be uniformly administered to patients with pneumonia when MRSA is isolated from respiratory specimens. A systematic review was conducted to evaluate the efficacy of the uniform administration of anti-MRSA drugs. Two researchers independently searched the literature as of December 2022, extracted relevant papers, and performed a meta-analysis. The outcomes were mortality and adverse events. No applicable randomized controlled trials were found during the study period, but four observational studies were extracted. The relative risk of mortality in the anti-MRSA group was 1.67 [95% confidence interval 0.65-4.30], which did not differ significantly from the non-administered group. Further investigation into the background of patients demonstrated that anti-MRSA drugs were administered to groups in which only MRSA was cultured. However, the pneumonia severity index did not differ from that in the non-treated group. No studies of adverse events were found. Our review did not find a beneficial contribution to mortality from uniform anti-MRSA medication to patients with pneumonia when MRSA was isolated from respiratory specimens. Factors determining risk-based individualized treatment should be validated as the future question., Competing Interests: Declaration of competing interest There are no COIs related to the present study, but Masafumi Seki declares the following COIs related to MRSA pneumonia: payment or honoraria for lectures from Pfizer Inc., Kyorin Pharmaceutical Co., Ltd., Shionogi Co., Ltd., MSD Co., Ltd, Daiichi Sankyo Co., Ltd., Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Asymptomatically nasal colonization by Staphylococcus aureus is a well-established risk factor for S. aureus infections. The aimed of the study was to identify the prevalence and factors associated with nasal carriage of S. aureus and Methicillin-resistant S. aureus (MRSA) from individuals residing in one Brazilian nursing home (NH). Three time-separate nasal swab collections were obtained from the elderly enrolled. The S. aureus isolates identified were submitted to Antimicrobial Susceptibility test (AST). The study showed a high prevalence of S. aureus (n = 9; 60%) and MRSA (n = 4; 26.7%) among elderly. Resistance to erythromycin was the most detected. S. aureus or MRSA colonization could not be associated to the data collected on demographics, personal habits, and medical history of the participants. Despite the small number of individuals enrolled, our study can contribute to improve the control of S. aureus and MRSA dissemination within the community, especially among the most vulnerable like the elderly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Light-triggered treatment approach has been regarded as an effective option for sterilization due to noninvasiveness, limited drug resistance, and minimized adverse effects. Herein, we designed and synthesized a functionalized cationic polymer, CR-PQAC, with croconaine bridging agent and quaternary ammonium groups for photothermal enhanced antimicrobial therapy under near-infrared irradiation. The quaternary ammonium group on the pendent chain endowing CR-PQAC the ability to effectively bind to bacteria. The CR-PQAC could self-assembles into micellar nanoparticles in aqueous solution, which exhibited strong absorption in the near-infrared (NIR) region, excellent photostability, and photothermal conversion efficiency of up to 43.8 %. Notably, the CR-PQAC nanoparticles presented remarkable antibacterial activity against both methicillin-resistant Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria with 808 nm laser irradiation. Moreover, the developed CR-PQAC has negligible dark cytotoxicity and good hemolytic compatibility against mammalian cells. Both in vitro and in vivo studies have demonstrated that the desirable antibacterial efficacy of CR-PQAC was obtained. Therefore, the proposed CR-PQAC may be a promising antimicrobial agent for NIR-enhanced killing bacterial., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H 2 S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with keratitis produces substantial amounts of phenol-soluble modulin α (PSMα). However, the role of PSMα in S. aureus keratitis remains unclear. We observed that PSMα-producing and PSMα-deficient strains could infect the cornea in our experimental mouse keratitis model; however, only the PSMα-producing strain delayed epithelial wound healing and induced stromal inflammation. PSMα induced damage to the epithelium, the release of alarmins IL-1α and IL-36α, and the expression of inflammatory chemokines by resident corneal cells in the mouse corneal organ culture. The IL-36 (but not IL-1) receptor antagonist attenuated mouse keratitis induced by PSMα-containing bacterial culture supernatants, as well as by infection with PSMα-producing S. aureus, suggesting that the corneal inflammations were dependent on IL-36. Recombinant PSMα elicited IL-36-dependent corneal inflammation in mice. Thus, PSMα and the subsequently released IL-36 are critical factors triggering inflammation during S. aureus keratitis., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Hydrogels made with depolymerized guar gum, oxidized with theoretical oxidation degrees of 20, 35 and 50 %, were obtained via Schiff's base reaction with N-succinyl chitosan. The materials obtained were subjected to characterization by FT-IR, rheology, swelling, degradation, and morphology. Additionally, their gelation time categorized all three hydrogels as injectable. The materials' swelling degrees in Phosphate-Buffered Saline (PBS) were in the range of 26-35 g of fluid/g gel and their pore size distribution was heterogeneous, with pores varying from 67 to 93 μm. All hydrogels degraded in PBS solution, but maintained around 40 % of their initial mass after 28 days, which was more than enough time for wound healing. The biomaterials were also flexible, self-repairing, adhesive and cytocompatible and presented intrinsic actions, regardless of the presence of additives or antibiotics, against gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli). However, the most pronounced bactericidal effect was against resistant Staphylococcus aureus - MRSA. In vivo assays, performed with 50 % oxidized gum gel, demonstrated that this material exerted anti-inflammatory effects, accelerating the healing process and restoring tissues by approximately 99 % within 14 days. In conclusion, these hydrogels have unique characteristics, making them excellent candidates for wound-healing dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Modification surface of chitosan nanoparticles using ZnO nanoparticles is important interest in drug delivery because of the beneficial properties. In this study, we proposed a chitosan/ZnO nanocomposite for the targeted delivery of antibacterial peptide (LL37). Synthesized LL37-loaded chitosan/ZnO nanocomposite (CS/ZnO/LL37-NCs) was based on the ionotropic gelation method. The antibacterial activity of the synthesized platform versus Methicillin-resistant Staphylococcus aureus (MRSA) was determined by the microdilution method in 10 mM sodium phosphate buffer. The biofilm formation inhibitory was also evaluated using microtiter plate method. In addition, the ability of CS/ZnO/LL37-NCs on the icaA gene expression level was assessed by the Real-Time PCR. The loading and release investigations confirmed the suitability of CS/ZnO-NCs for LL37 encapsulation. Results showed 6 log 10 CFU/ml reduction in MRSA treated with the CS/ZnO/LL37-NPs. Moreover, CS/ZnO/LL37-NCs showed 81 % biofilm formation inhibition than LL37 alone. Also, icaA gene expression decreased 1-fold in the face of CS/ZnO/LL37-NCs. In conclusion, the modification surface of chitosan nanoparticles with ZnO nanoparticles is a suitable chemical platform for the delivery of LL37 that could be used as a promising nanocarrier for enhancing the delivery of antibacterial peptide and improving the antibacterial activity of LL37., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)