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Per- and poly-fluoroalkyl substances (PFAS) are an emerging class of persistent organic pollutants that are widespread in aquatic ecosystems and pose a serious threat to aquatic organisms. It is thus crucial to explore the toxicity mechanisms of PFAS to submerged macrophytes and biofilms. In this study, Vallisneria natans (V. natans) was exposed to environmentally relevant concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulphonate (PFOS). Results showed that PFAS induced the excessive production of reactive oxygen species, triggering antioxidant responses. V. natans exhibited an improved stress tolerance by altering the biosynthesis of several plant secondary metabolites and the histidine, arginine, proline pathways in response to PFAS exposure. Moreover, PIP1-1, PIP2-2, SLAH1 and SLAH2 genes were upregulated, indicating the activation of aquaporins and slow-type anion channels. The uptake of PFOA and PFOS by V. natans was 41.74 % and 52.31 %, respectively. Notably, PFAS bound to functional proteins (GSTF10), promoting the detoxification of plants. Exposure to PFAS also altered the structure of biofilms by inducing the synthesis of large amounts of polysaccharides and proteins. The diversity and richness of the microbial community within periphytic biofilms changed significantly. These results provide a comprehensive description of the responses of aquatic plants and periphytic biofilms to PFAS and the removal mechanism of PFAS, contributing to the environmental risk assessments and removal of PFAS in aquatic ecosystems., 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. Published by Elsevier B.V.)

In modern times, many antibiotics have become less effective as microorganisms develop resistance. Besides antibiotic resistance, another bacterial strategy that contributes to the capacity to withstand antimicrobials is biofilm formation. Because of these bacterial survival strategies, the desired response cannot be achieved with conventional treatment. Considering the limited discovery of new compounds, the most logical approach is to reconstruct existing antimicrobial molecules with nano-drug delivery systems. With this scientific approach, the aim of the study is to develop a novel nano-antibiotic hydrogel formulation containing silver nanoparticles, chitosan, and amoxicillin. Endodontic disease was used as a model of biofilm-mediated infection, and the antibacterial activity of nano-antibiotic hydrogel was evaluated with the E. faecalis standard bacterial strain. By adopting the Box-Behnken design for the optimisation of formulation variables, an innovative pharmaceutical formulation with antimicrobial and antibiofilm activity was successfully obtained. Further characterisation studies, including nanoparticle characterisation, in vitro cytotoxicity, and ex vivo activity studies, were carried out on dental samples using the optimised formulation. All results were compared with antimicrobial agents routinely used in endodontic treatment. The findings mainly conclude that the optimised nano-antibiotic hydrogel may be an alternative antimicrobial formulation since it is non-cytotoxic and exhibits high antibiofilm activity., 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 efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H 2 O 2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H 2 O 2 and Fc liberated Fe 3+ that was further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe 3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential., 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.)

Microplastics, pervasive contaminants from plastic, present significant challenges to wastewater treatment processes. This review critically examines the interactions between microplastics and biofilm-based treatment technologies, specifically focusing on the concepts of "biofilm on microplastics" and "microplastics in biofilm". It discusses the implications of these interactions in contaminant removal and process performance. Advanced characterization techniques, including morphological characterization, chemical composition analysis, and bio-information analysis, are assessed to elucidate the complex interplay between microplastics and biofilms within biofilters, biological aerated filters (BAFs), rotating biological contactors (RBCs), and moving bed biofilm reactors (MBBRs). This review synthesizes current research findings, highlighting that microplastics can either hinder or enhance the treatment processes, contingent on their concentration, physicochemical properties, and the specific biofilm technology employed. The insights gained from this review are essential for developing strategies to mitigate the adverse effects of microplastics and for optimizing the design and operation of wastewater treatment., 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.)

Rapid regeneration of the injured tissue or organs is necessary to achieve the usual functionalities of the damaged parts. However, bacterial infections delay the regeneration process, a severe challenge in the personalized healthcare sector. To overcome these challenges, 3D-printable multifunctional hydrogels of Zn/tannic acid-reinforced glycol functionalized chitosan for rapid wound healing were developed. Polyphenol strengthened intermolecular connections, while glutaraldehyde stabilized 3D-printed structures. The hydrogel exhibited enhanced viscoelasticity (G'; 1.96 × 10 4  Pa) and adhesiveness (210 kPa). The dual-crosslinked scaffolds showed remarkable antibacterial activity against Bacillus subtilis (∼81 %) and Escherichia coli (92.75 %). The hydrogels showed no adverse effects on human dermal fibroblasts (HDFs) and macrophages (RAW 264.7), indicating their superior biocompatibility. The Zn/TA-reinforced hydrogels accelerate M2 polarization of macrophages through the activation of anti-inflammatory transcription factors (Arg-1, VEGF, CD163, and IL-10), suggesting better immunomodulatory effects, which is favorable for rapid wound regeneration. Higher collagen deposition and rapid re-epithelialization occurred in scaffold-treated rat groups vis-à-vis controls, demonstrating superior wound healing. Taken together, the developed multifunctional hydrogels have great potential for rapidly regenerating bacteria-infected wounds in the personalized healthcare sector., Competing Interests: Declaration of competing interest The authors declare that no conflicts of financial interests or personal relationships have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although cobalt (Co) plays a significant role in the transition to low-carbon technologies, its environmental impact remains largely unknown. This study examines Co impacts on the prokaryotic communities within river biofilms to evaluate their potential use as bioindicators of Co contamination. To this end, biofilms were cultivated in artificial streams enriched with different environmental Co concentrations (0.1, 0.5, and 1 μM Co) over 28 days and examined for prokaryotic abundance and diversity via quantitative PCR and DNA-metabarcoding every 7 days. The prokaryotic community's resilience was further investigated after an additional 35 days without Co contamination. The prokaryotic communities were affected by 0.5 and 1 μM Co from the onset of biofilm colonization. The biofilm biomass was comparable between treatments, but the community composition differed. Control biofilms were dominated by Cyanobacteria and Planctomycetes, whereas Bacteroidetes dominated the Co-contaminated biofilms. Potential functional redundancy was observed through the implementation of carbon fixation alternatives by non-photosynthetic prokaryotes in biofilms exposed to high Co concentrations. No structural resilience was observed in the biofilms after 35 days without Co contamination. Measuring the prokaryotic community structural response using molecular approaches appears to be a promising method for assessing shifts in water quality owing to Co contamination., 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 B.V. All rights reserved.)

The biofilm-mediated implant infections pose a huge threat to human health. It is urgent to explore strategies to reverse this situation. Herein, we design 3-amino-1,2,4-triazole-5-thiol (ATT)-modified gold nanoclusters (AGNCs) to realize biofilm-targeting and near-infrared (NIR)-II light-responsive antibiofilm therapy. The AGNCs can interact with the bacterial extracellular DNA through the formation of hydrogen bonds between the amine groups on the ATT and the hydroxyl groups on the DNA. The AGNCs show photothermal properties even at a low power density (0.5 W/cm 2 ) for a short-time (5 min) irradiation, making them highly effective in eradicating the biofilm with a dispersion rate up to 90 %. In vivo infected catheter implantation model demonstrates an exceptional high ability of the AGNCs to eradicate approximately 90 % of the bacteria encased within the biofilms. Moreover, the AGNCs show no detectable toxicity or systemic effects in mice. Our study suggests the great potential of the AGNCs for long-term prevention and elimination of the biofilm-mediated 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 © 2024 Elsevier Inc. All rights reserved.)

The biofilm architecture is significantly influenced by external environmental conditions. Biofilms grown on drinking water distribution systems (DWDS) are exposed to environmental contaminants, including parabens, and disinfection strategies, such as chlorine. Although changes in biofilm density and culturability from chemical exposure are widely reported, little is known about the effects of parabens and chlorine on biofilm morphology and architecture. This is the first study evaluating architectural changes in Stenotrophomonas maltophilia colony biofilms (representatives of bacterial communities presented in DWDS) induced by the exposure to methylparaben (MP) at environmental (15 μg/L) and in-use (15 mg/L) concentrations, and chlorine at 5 mg/L, using widefield epi-fluorescence mesoscopy with Mesolens. The GFP fluorescence of colony biofilms allowed the visualization of internal structures and Nile Red fluorescence permitted the inspection of the distribution of lipids. Our data show that exposure to MP triggers physiological and morphological adaptation in mature colony biofilms by increasing the complexity of internal structures, which may confer protection to embedded cells from external chemical molecules. These architectural modifications include changes in lipid distribution as an adaptive response to MP exposure. Although chlorine exposure affected colony biofilm diameter and architecture, the colony roundness was completely affected by the simultaneous presence of MP and chlorine. This work is pioneer in using Mesolens to highlight the risks of exposure to emerging environmental contaminants (MP), by affecting the architecture of biofilms formed by drinking water (DW) bacteria, even when combined with routine disinfection strategies., 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. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Helicobacter pylori (H. pylori) infections are on the rise, presenting a significant global health challenge. Mass Galla chinesis et camelliae Fermentata (Chinese gall leaven, CGL), a traditional Chinese medicinal product made from the fermentation of Rhus chinensis Mill., is frequently employed to address digestive system ailments. Contemporary pharmacological research reveals that CGL exhibits anti-inflammatory, anti-diarrheal, and enzyme-inhibitory activities and holds potential as a treatment for H. pylori infections. However, the precise mechanisms underlying CGL's efficacy against H. pylori remain to be fully elucidated., Aim: The objective of the study is to evaluate CGL's ability to disrupt the H. pylori biofilm and to explore its synergistic potential with antibiotics in targeting the biofilm-efflux pump system, a mechanism implicated in bacterial resistance., Methords: The study determined the Minimum Inhibitory Concentration (MIC) of CGL and metronidazole against H. pylori and evaluated their effects on H. pylori biofilms using an in vitro model. Structural changes induced by drug interventions were compared to those in untreated and antibiotic-treated models through scanning electron microscopy and laser confocal microscopy. The accumulation of H33342 dye in planktonic and biofilm H. pylori before and after drug treatment was assessed to evaluate cell viability and biofilm disruption. The study also involved adding experimental drugs to a biofilm H. pylori medium containing D-glucose, measuring glucose concentrations post-intervention using the glucose oxidase method, and calculating changes in glucose uptake. Finally, the relative expression levels of several genes in planktonic and biofilm H. pylori treated with CGL alone or in combination with antibiotics were measured to understand the impact on the biofilm-efflux pump system., Results: Both CGL alone and in combination with metronidazole demonstrated effective disruption of H. pylori biofilms. The combination therapy was particularly effective in reducing the biofilm transfer-enhancing effect of metronidazole and decreasing SpoT expression in the 'SpoT-(p)ppGpp' pathway, especially in biofilms. It showed a greater inhibition of the 'σ54-gluP-sugar uptake' pathway, with significant reductions in rpoN and gluP expression under biofilm conditions compared to CGL or metronidazole alone. The treatment also suppressed H. pylori proliferation and may have altered glucose uptake mechanisms. Moreover, it significantly inhibited the 'hp0939/hp0497/hp0471-RND efflux pump' pathway, with a notable reduction in gene expression compared to the 1/2 MIC metronidazole treatment., Conclusion: This study demonstrates that CGL effectively hinders the development of drug resistance in H. pylori by targeting biofilm formation and critical molecular pathways associated with antibiotic resistance. The synergistic effect of combining CGL with metronidazole notably enhances biofilm disruption and inhibits the bacterium's metabolic and reparative mechanisms. Further in vivo studies are needed to confirm these results and to investigate additional mechanisms of CGL's action., 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 B.V. All rights reserved.)

Endowing titanium surfaces with multifunctional properties can reduce implant-related infections and enhance osseointegration. In this study, titanium dioxide nanotubes with strontium doping (STN) were first created on the titanium surface using anodic oxidation and hydrothermal synthesis techniques. Next, casein phosphopeptide (CCP) and an antimicrobial peptide (HHC36) were loaded into the STN with the aid of vacuum physical adsorption (STN-CP-H), giving the titanium surface a dual function of "antimicrobial-osteogenic". The surface of STN-CP-H has a suitable roughness and good hydrophilicity, which is conducive to osteoblasts. STN-CP-H had a 99 % antibacterial rate against S. aureus and E. coli and effectively prevented the growth of bacterial biofilm. Meanwhile, the antibacterial mechanism of STN-CP-H was initially explored with the help of transcriptome sequencing technology. STN-CP-H could greatly increase osteoblast adhesion, proliferation, and expression of osteogenic markers (alkaline phosphatase, runt-related transcription) when CCP and Sr worked together synergistically. In vivo, the STN-CP-H coating could effectively promote new osteogenesis around titanium implant bone and had no toxic effects on heart, liver, spleen, lung and kidney tissues. A potential anti-infection bone healing material, STN-CP-H bifunctional coating developed in this work efficiently inhibited bacterial infection of titanium implants and encouraged early osseointegration., 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.)

Reducing antibiotic levels in soil ecosystems is vital to curb the dissemination of antimicrobial resistance genes (ARGs) and mitigate global health threats. However, gaps persist in understanding how antibiotic resistome can be suppressed during antibiotic degradation. Herein, we investigate the efficacy of a biochar biofilm incorporating antibiotics-degrading bacterial strain (Arthrobacter sp. D2) to mitigate antibiotic resistome in non-manured and manure-amended soils with sulfadiazine (SDZ) and trimethoprim (TMP) contamination. Results show that biofilm enhanced SDZ degradation by 83.0% within three days and increased TMP attenuation by 55.4% over 60 days in non-manured soils. In the non-manured black soil, the relative abundance of ARGs increased initially after biofilm inoculation. However, by day 30, it decreased by 20.5% compared to the controls. Moreover, after 7 days, biofilm reduced TMP by 38.5% in manured soils and decreased the total ARG abundance by 19.0%. Thus, while SDZ degradation did not increase sulfonamide resistance genes, TMP dissipation led to a proliferation of insertion sequences and related TMP resistance genes. This study underscores the importance of antibiotic degradation in reducing related ARGs while cautioning against the potential proliferation and various ARGs transfer by resistant microorganisms., 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.)

Vibrio parahaemolyticus and microplastics are prevalent in the ocean. Bacteria attach onto plastic particles, forming harmful biofilms that collectively threaten bivalve health. This study investigates the interaction between polyamide microplastics (PA: particle size 38 ± 12 µm) and V. parahaemolyticus, as well as their combined impact on thick-shelled mussels (Mytilus coruscus). We introduced 10 11 CFU/L of V. parahaemolyticus into varying PA concentrations (0, 5, 50, and 500 particles/L) to observe growth over 14 h and biofilm formation after 48 h. Our findings indicate that microplastics suppress biofilm formation and virulence gene expression. Four treatments were established to monitor mussel responses: a control group without PA or V. parahaemolyticus; a group with 50 particles/L PA; a group with 10 11 CFU/L V. parahaemolyticus; and a co-exposure group with both 50 particles/L PA and 10 11 CFU/L V. parahaemolyticus, over a 14-day experiment. However, combined stress from microplastics and Vibrio led to immune dysregulation in mussels, resulting in intestinal damage and microbiome disruption. Notably, V. parahaemolyticus had a more severe impact on mussels than microplastics alone, yet their coexistence reduced some harmful effects. This study is the first to explore the interaction between microplastics and V. parahaemolyticus, providing important insights for ecological risk 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 © 2024 Elsevier B.V. All rights reserved.)

The rapid emergence and spread of multidrug-resistant (MDR) Gram-positive pathogens present a significant challenge to global healthcare. Methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern because of its high resistance to most antibiotics. Based on our previously reported chemical structure of compound 62, a series of novel derivatives were synthesized and evaluated for their antibacterial activities. We found that some of these derivatives displayed effective antibacterial activity against Gram-positive pathogens, with minimal cytotoxicity (CC 50 >100 μM) and hemolytic activity (HC 50 >200 μM). Among these derivatives, the minimum inhibitory concentration (MIC) of 62-7c against Gram-positive bacterial isolates ranged from 6.25 to 25 μM. This derivative also exhibited significant synergistic antibacterial effects with daptomycin both in vitro and in vivo, with an ability to eradicate planktonic and persister cells of MRSA. Additionally, 62-7c inhibited biofilm formation and eradicated mature biofilms of MRSA. Mechanistic studies revealed that 62-7c inhibited the YycG kinase activity and disrupted the cell membrane by binding to cardiolipin (CL), leading to cell death. Importantly, no development of drug resistance was observed even after 20 serial passages. Furthermore, 62-7c exhibited high biosafety and potent effectiveness in combating infections in both mouse pneumonia and mouse wound models infected with MRSA. Thus, our study revealed that 62-7c has the potential to serve as a novel antibacterial agent for treating MRSA 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 © 2024 Elsevier Masson SAS. All rights reserved.)

Aggregation is a crucial factor in bacterial biofilm formation, and comprehending its properties is vital for managing waterborne antibiotic-resistant bacteria. In this study, we examined Methicillin-resistant Staphylococcus aureus (MRSA) cell aggregation under varying conditions and assessed the inactivation efficiency of a novel disinfection method, micro-nano bubbles plasma-activated water via ultrasonic stirring cavitation (MPAW-US), on aggregated MRSA cells. Aggregation efficiency increased over time and at low salt concentrations but diminished at higher concentrations. Elevated MRSA cell aggregation in actual water samples represented significant real-life biohazard risks. Unlike conventional disinfection, MPAW-US treatment exhibited minimal change in the inactivation rate constant despite protective outer layers. Enhanced inactivation efficiency results from the synergistic effects of increased intracellular oxidative stress damage and extracellular substance disruption, triggered by ultrasound-activated micro-nano bubbles that improve PAW reactivity and applicability. This approach neither induced MRSA cross-resistance to unfavorable conditions nor increased toxicity or regrowth potential of aggregative MRSA, utilizing ATP levels as potential regrowth capability indicators. Ultimately, this energy-efficient disinfection technology functions effectively across diverse temperature ranges, showcasing exceptional sterilization and nutritional bean sprout production after cyclic filtering, thereby promoting wastewater sustainability amidst carbon emission concerns., 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 abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 μg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds 4h and 17e displayed excellent antibacterial activity against Gram-positive bacteria (MICs = 1-4 μg/mL) with weak hemolytic activity and good membrane selectivity. Additionally, compounds 4h and 17e had rapid bactericidal properties, low resistance frequency, good plasma stability, and strong capabilities of inhibiting and eliminating bacterial biofilms. Mechanistic studies revealed that compounds 4h and 17e could effectively disrupt the integrity of bacterial cell membranes, and accompanied by an increase in intracellular reactive oxygen species and the leakage of proteins and DNA, ultimately leading to bacterial death. Notably, compound 4h exhibited comparable in vivo antibacterial potency in a mouse septicemia model infected by Staphylococcus aureus ATCC43300, as compared to vancomycin. These findings indicated that 4h might be a promising antibacterial candidate to combat antimicrobial resistance., Competing Interests: Declaration of competing interest The authors declare that this study was carried out only with public funding. There is no funding or no agreement with commercial for profit firms., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Salmon aquaculture is the fastest growing food production system in the world. Deficiencies in the quality or safety of salmon can have global repercussions. Controlling food safety aspects during production is therefore essential. Here, we investigate the state of hygiene in a salmon processing plant using next generation sequencing and classical culture-dependent methods to characterize the surface microbiota before and after cleaning and disinfection (C&D) at ten surface sampling points. Total aerobic counts revealed an average reduction in the bacterial loads of 1.1 log CFU/cm 2 by C&D. The highest relative abundance in the core microbiota before C&D was assigned to Acinetobacter, Mycoplasmataceae, Pseudomonas and Enterobacteriaceae in descending order. After C&D, we observed a significant increase in the relative abundance of Pseudomonas (p < 0.05). However, variations were found between conveyors, processing machines and drains. To assess the efficacy of commercial disinfectants, we performed susceptibility assays using advanced robotic high-throughput technologies and included foodborne bacteria which may affect food safety and spoilage. These included 128 Pseudomonas isolates, 46 Aeromonas isolates and 59 Enterobacterales isolates sampled from the salmon processing plant. Generally, minimum inhibitory concentrations (MICs) of the disinfectants were below the user concentration recommended by the producer for most isolates. BacTiter-Glo biofilm assays revealed that 30 min exposure to six out of eight commercial disinfectants resulted in an average reduction of relative luminescence >95 % in 59 single-species biofilms selected for screening. However, disinfection alone may not always be sufficient to eradicate biofilms completely. C&D routines must therefore be continuously assessed to maintain food safety and quality. The results from this study can contribute to understand and improve the state of hygiene in salmon processing environments., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Biofilm formation in natural environments involving complex multi-structural arrangements hinders challenges in antimicrobial resistance. This study investigated the antimicrobial resistance potential of grapefruit seed extract (GSE) by examining the formation of mono-, dual-, and multi-species biofilms. We also explored the counterintuitive effect in response to GSE at various concentrations, including minimum inhibitory concentration (MIC) and sub-MIC (1/2 and 1/4 MIC). The results of the swimming and swarming motility tests revealed increased motility at the sub-MIC of GSE. The crystal violet assay demonstrated increased biofilm formation in multi-species biofilms, highlighting the synergistic effect of Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes. At the MIC concentration of GSE, field emission scanning electron microscopy (FE-SEM) revealed cell morphology damage, while sub-MIC increased biofilm formation and architectural complexity. Multi-species biofilms demonstrated greater biofilm-forming ability and antimicrobial resistance than mono-species biofilms, indicating synergistic interactions and enhanced resilience. These findings highlight the importance of understanding biofilm dynamics and antimicrobial resistance to ensure environmental safety., 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. Published by Elsevier B.V.)

Despite the measures employed, fracture-related infections remain a concern after fracture fixation worldwide. Recently, the role of tranexamic acid as a protective drug against postsurgical infections in joint replacement and orthopedic trauma surgery has been proposed, where tranexamic acid has been associated with less surgical wounds complications and infectious complications including periprosthetic joint infection. The mechanism through which tranexamic acid exerts a protective effect against peri-implant infection is still the subject of debate. Although some authors hypothesize an indirect effect inhibiting the formation of postoperative hematoma, there are several studies that show a direct antibacterial effect of the drug against the capacity of bacterial aggregation, even avoiding biofilm formation, favoring the immune response of the host and the action of antibiotics. The purpose of this narrative review is to show the current role of tranexamic acid in orthopedic trauma, specifically its relationship with the prevention of infections related to implants., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Soft tissue and bone infections continue to be a serious complication in orthopedic and trauma surgery. Both can lead to a high burden for the patients and the healthcare system. Musculoskeletal infections can be induced by intraoperative contamination, bacterial contamination of open wounds or hematogenous bacterial spread. During the recent decades, advances were achieved in the understanding of pathogenesis and antibiotic resistance. Despite some progress in the diagnosis and advancing of therapeutic concepts, groundbreaking successful improvement of treatment concepts is still missing. Current therapy concepts are based on the two pillars consisting of surgical debridement with joint or bone reconstruction as well as prolonged antibiotic therapy. An improved understanding of both host and pathogen-related factors leading to treatment failure is essential in musculoskeletal infections. Therefore, this review aims to give an overview of pathogen-related pathophysiology in musculoskeletal infections. It describes defense strategies of pathogens such as (1) biofilm, its development, characteristics, and treatment options. In addition, (2) characteristics of small colony variants and (3) intracellular bacteria are highlighted. Lastly (4) an outlook for potential and promising future therapeutic strategies is provided., 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. Published by Elsevier Ltd.)

Oral diseases are often associated with bacterial and fungal pathogens such as Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Candida albicans. This research explored a novel approach to addressing these pathogens by synthesizing zinc oxide nanoparticles (ZnO NPs) coated with rutin (RT), a plant-derived compound. The synthesized ZnO-RT NPs were comprehensively characterized using UV-Vis spectrophotometer, SEM, and EDAX techniques to confirm their structural composition. The antioxidant potential was assessed through free radical scavenging assays. Additionally, the antimicrobial activity of ZnO-RT NPs was evaluated using a zone of inhibition assay against oral pathogens. Molecular docking studies with the Autodock tool were performed to elucidate the interactions between RT and the receptors of oral pathogens. The findings demonstrated that ZnO-RT NPs exhibited robust free radical scavenging activity. Furthermore, they showed significant antimicrobial activity with a minimal inhibitory concentration of 40 μg/mL against oral pathogens. ZnO-RT NPs also displayed dose-dependent anticancer effects on human oral cancer cells at concentrations of 10, 20, 40, and 80 μg/mL. Mechanistic insights into the anticancer activity on KB cells revealed the upregulation of apoptotic genes. This study underscores the promising potential of ZnO-RT NPs for dental applications due to their strong antioxidant, anticancer, and antimicrobial properties. These nanoparticles offer a hopeful prospect for addressing oral pathogen challenges and enhancing overall oral health., (© 2024 Wiley Periodicals LLC.)

Chocolate is one of the most popular treats in the world. Debate over the potential benefits of its consumption has made chocolate a widely researched health topic. This article reviews the general health benefits of chocolate consumption, focusing on its involvement with the oral microbiota, caries development, and biofilm control, and discusses the potential negative consequences of excess chocolate consumption., Competing Interests: No conflicts of interest reported.

Biofilm formation on food packaging surfaces is a major issue in the industry, as it leads to contamination, reduces shelf life, and poses risks to human health. To mitigate these effects, developing smart coatings that can actively sense and combat microbial growth has become a critical research focus. This study is motivated by the need for intelligent packaging solutions that integrate antimicrobial agents and sensors for real-time contamination detection. It is hypothesized that combining conducting polymers (CPs) with nanomaterials can enhance antimicrobial efficacy while maintaining the mechanical integrity and environmental stability required for food packaging applications. Through the application of numerous technologies like surface modification, CP-nanoparticle integration, and multilayered coating, the antimicrobial performance and sensor capabilities of these materials were analyzed. Case studies showed a 90% inhibition of bacterial growth and a tenfold decrease in viable bacterial counts with AgNPs incorporation, extending strawberries' shelf life by 40% and maintaining fish freshness for an additional 5 days. Moreover, multilayered CP coatings in complex systems have been shown to reduce oxidative spoilage in nuts and dried fruits by up to 85%, while maintaining the quality of leafy greens for up to 3 weeks under suboptimal conditions. Environmental assessments indicated a 30% reduction in carbon footprint when CP coatings were combined with biodegradable polymers, contributing to a more transparent and reliable food supply chain. CP-based films integrated with intelligent sensors exhibit high sensitivity, detecting ammonia concentrations below 500 ppb, and offer significant selectivity for sensing hazardous gases. These findings indicate that CP-based smart coatings markedly enhance food safety and sustainability in packaging applications., (© 2024 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Background: Considering that antimicrobial resistance among oral pathogens is a significant concern in dental practice, with broader implications for overall health due to the oral microbiota serving as a reservoir for antibiotic resistance genes (ARGs), research into natural products is crucial for addressing this issue., Objective: This study aimed to evaluate tea tree oil (TTO) and chitosan (CH) performance against oral pathogens, including mixed-species biofilm, and its effects on bacteria growth, in addition to chemical characterization and cytotoxicity of TTO., Methods: Tea Tree Oil and low molecular weight chitosan were used in this study. The chemical composition of TTO was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). To evaluate TTO's antimicrobial properties, time-kill and cell viability assays were conducted. Additionally, minimum inhibitory concentration (MIC), minimum microbiocidal concentration (MMC), checkerboard, and biofilm assays were performed using TTO and CH alone and in combination., Results: TTO chromatography peaks found consistent with the standard ISO4730:2017 and literature. TTO and CH exhibited inhibitory activity against all tested microorganisms. The predominantly microbiostatic activity of TTO is probably related to terpinen-4-ol associated with terpinene. The oil at MIC value was able to delay the log phase of Aggregatibacter actinomycetemcomitans growth. Fibroblasts (L929) viability remained above 70 % during 24 h for TTO concentrations ranging from 0.5 to 0.0625 mg/ml. TTO-CH combination showed a synergistic activity (FIC = 0.5) against A. actinomycetemcomitans and Streptococcus sanguinis, at a concentration of 0,25MIC for both species. The compounds at MIC concentration inhibited both monospecies and mixed-species biofilms studied bacteria to the same extent as the azithromycin control., Conclusion: TTO and CH demonstrated efficacy in combating oral pathogens and TTO-CH combination offers a promising approach to confront microbial resistance in the oral environment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ana Carolina Morais Apolonio reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG- APQ-01165-22). If there are other authors, they 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.)

Today, many infections in plants are related to biofilm-developing bacteria. These infections can result in severe agricultural losses. Thus, this study aims to investigate the synergistic antibiofilm activity of Thymus vulgaris extract on the inherent antibacterial properties of ZnO nanoparticles against Erwinia amylovora and Pseudomonas syringae pv. syringae. Additionally, to gain insight into the molecular mechanisms of phytocompounds' antibacterial activity, the molecular interactions of T. vulgaris phytochemicals with the TolC protein and TonB-dependent siderophore receptor were investigated through in-silico studies. Green-synthesized ZnO NPs (ZnO@GS) and chemically synthesized ZnO (ZnO@CHS) were evaluated using XRD and SEM techniques, showing a crystalline structure for both powders with average sizes of 50, and 40 nm, respectively. According to FT-IR and EDS spectroscopy, ZnO@GS was covered with thyme extract. Based on the in vitro results, all samples of ZnO NPs exhibited considerable antibacterial activity against both bacteria. At the same time, thyme aqueous extract alone proved considerably less effective at all tested concentrations. Compared to ZnO@CHS and thyme extract, the antibacterial efficacy of ZnO@GS against E. amylovora (MIC = 512 μg/mL) and P. syringae pv. syringae (MIC = 256 μg/mL) was significantly improved upon surface covering with thyme phytocompounds. Moreover, their antibiofilm properties were enhanced by almost 20 % compared to ZnO@CHS. In addition, molecular docking investigations showed that most of the phytocompounds could form stable interactions with the TonB-dependent siderophore receptor (P. syringae) plug domain and the TolC (E. amylovora) external channel. In vitro and in silico studies demonstrate that using the green approach for synthesizing ZnO NPs via thyme extract can notably boost its antibacterial and antibiofilm effects on the tested phytopathogenic 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 © 2024 Elsevier Ltd. All rights reserved.)

The quorum-sensing (QS) system of Pseudomonas aeruginosa dominates the pathogenicity of the acute or chronic infection process. Hence, curbing the pathogenicity of P. aeruginosa by targeting QS system is an ideal strategy. This study aims to identify potential anti-virulence compounds that can effectively disrupt the QS system of P. aeruginosa using a combination of virtual screening and experimental validation techniques. We explored inhibitory effect of isovanillin obtained by virtual screening on P. aeruginosa QS regulated virulence factors extracellular protease, biofilm, and pyocyanin. Results displayed that isovanillin could inhibit the virulence phenotypes regulated by the las- and pqs-QS systems of P. aeruginosa. The synthesis of extracellular proteases, pyocyanin, and biofilm formation by P. aeruginosa were dramatically inhibited by sub-MICs doses of isovanillin. The results of RNA sequencing and quantitative PCR revealed that the QS-activated genes down-regulated by subinhibitory isovanillin in the transcriptional evels. Furthermore, the presence of isovanillin increased the susceptibility of drug-resistant P. aeruginosa to kanamycin, meropenem, and polymyxin B. Treatment of isovanillin as a monotherapy significantly decreased the mortality of C. elegans in P. aeruginosa PAO1 or UCBPP-PA14 (PA14) infection. Our study reported the anti-virulence activity of isovanillin against P. aeruginosa, and provided a structural foundation for developing anti-virulence drugs targeting the QS system of P. aeruginosa., Competing Interests: Declaration of competing interest The author asserts that the study was carried out without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as β-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with β-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 μg/ml) and β-Glucosidase (112.5 ± 17.6 μg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 μg/ml). Notably, treatment with β-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or β-glucosidase can be a potential strategy to improve the TB therapeutic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships with individual or other organization that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study presents the green synthesis and comprehensive characterization of platinum nanoparticles (PtNPs) using Desmostachya bipinnata (Db) extract, incorporated into two innovative mouthwash formulations (MW1 and MW2). UV-Vis spectroscopy confirmed the successful synthesis of PtNPs, with distinct absorption peaks between 250 and 600 nm. Fourier-transform infrared (FTIR) spectroscopy identified hydroxyl and carbonyl functional groups, critical for the bioreduction and stabilization of PtNPs. High-resolution transmission electron microscopy (HR-TEM) revealed uniformly dispersed, spherical nanoparticles with a size range of 10-20 nm, while dynamic light scattering (DLS) confirmed a hydrodynamic diameter of 10-30 nm and a low polydispersity index (PDI) of 0.238, indicating excellent stability. Both formulations exhibited robust antimicrobial, antibiofilm, and anti-plaque properties, with MW2 showing superior efficacy, particularly against Staphylococcus aureus and Escherichia coli, as well as a notable 70 % reduction in biofilm formation and a 60 % plaque reduction within 2 h of treatment. The study underscores the potential of Desmostachya bipinnata-derived PtNPs as a promising alternative to conventional mouthwash, offering enhanced antimicrobial efficacy, biofilm disruption, and plaque prevention, alongside excellent stability and biocompatibility for oral healthcare applications., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present study aimed to evaluate the anti-staphylococcal, antibiofilm, cytotoxicity and trypanocidal activity, mechanisms of parasite death and immunomodulatory effect of CrataBL encapsulated into liposomes (CrataBL-Lipo). CrataBL-Lipo were prepared by the freeze-thaw technique and characterized. Anti-staphylococcal and antibiofilm activities of CrataBL and CrataBL-Lipo were evaluated against standard and clinical strains of Staphylococcus aureus susceptible and resistant. Thus, broth microdilution method was performed to determine the Minimum Inhibitory Concentration (MIC). Antibiofilm activity at subinhibitory concentrations was evaluated using the crystal violet staining method. Cytotoxicity of CrataBL-Lipo was verified in L929 fibroblasts and J774A.1 macrophages by determining the inhibitory concentration necessary to kill 50 % of cells (IC 50 ). Trypanocidal activities of CrataBL-Lipo was evaluated in Trypanosoma cruzi and the efficacy was expressed as the concentration necessary to kill 50 % of parasites (EC 50 ). The mechanisms of parasite death and immunomodulatory effect of CrataBL-Lipo were evaluated using flow cytometry analysis. CrataBL-Lipo presented Ø of 101.9 ± 1.3 nm (PDI = 0.245), ζ of +33.8 ± 1.3 mV and %EE = 80 ± 0.84 %. CrataBL-Lipo presented anti-staphylococcal activity (MIC = 0.56 mg/mL to 0.72 mg/mL). CrataBL-Lipo inhibited 45.4 %-75.6 % of biofilm formation. No cytotoxicity of CrataBL-Lipo was found (IC 50  > 100 mg/L). CrataBL-Lipo presented EC 50 of 1.1 mg/L, presenting autophagy, apoptosis and necrosis as death profile. In addition, CrataBL-Lipo reduced the production of IL-10 and TNF-α levels, causing an immunomodulatory effect. CrataBL-Lipo has a therapeutic potential for the treatment of staphylococcal infections and Chagas disease exhibiting a high degree of selectivity for the microorganism, and immunomodulatory properties., 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.)

Objective: In recent years, significant progress has been made in the field of nanotechnology for the treatment and prevention of biofilm formation and Multidrug-resistant bacteria (MDR). MDR bacteria challenges is hazardous when microorganisms induce the formation of biofilms, which amplify resistance to antibiotics and promote the development of multidrug-resistant conditions. The unique physicochemical properties of certain nanomaterials make nanotechnology a promising option for combating MDR infections. Several studies have introduced nanomaterials with different antibacterial mechanisms that can effectively destroy MDR bacteria and their biofilms. This study reviews the research results, focusing on the various nanoparticle mechanisms that target bacterial structures., Method: To accomplish this study, we conducted investigations to gather articles and relevant studies from validated medical databases such as Scopus, PubMed, Google Scholar, and Web of Science. The selected publications from 2007 to 2023. In this review, we provide a brief overview of nanoparticles, their mechanisms, and how they function against the structure of bacteria. Furthermore, we discuss the recent advancements in using certain nanoparticles to combat infection-induced biofilms and complications caused by multidrug resistance., Finding: Our findings demonstrate that various nanoparticles have the potential to effectively overcome bacterial infectious diseases by targeting biofilms and antibiotic-resistant strains. Additionally, the development of a new drug delivery approach based on nanosystems shows promise in overcoming antibiotic resistance and biofilms., 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.)

Pseudomonas aeruginosa (P. aeruginosa), a Gram-negative opportunistic pathogen, poses significant treatment challenges due to its antibiotic resistance and biofilm formation. This study investigates the anti-bacterial and anti-biofilm activities of chemically synthesized selenium nanoparticles (SeNPs) against P. aeruginosa. SeNPs were synthesized using ascorbic acid as a reducing agent and characterized. Biofilm formation was quantified using a modified microtiter plate method, and the anti-biofilm efficacy of SeNPs was evaluated using confocal microscopy and SEM. The P. aeruginosa isolates exhibited high resistance to piperacillin-tazobactam (60 %) and ceftazidime (59 %). SeNPs demonstrated a round shape with a diameter of 15-18 nm. UV-Vis spectra showed a peak at 275 nm, and XRD analysis revealed crystalline peaks corresponding to selenium. The FTIR spectra confirmed the presence of various functional groups. SeNPs significantly reduced biofilm formation in a dose-dependent manner, with MIC50 and MIC90 values of 60 μg/mL and 80 μg/mL, respectively. Confocal microscopy and SEM analysis showed a notable decrease in biofilm thickness and bacterial adherence post-SeNPs treatment. These findings suggest that SeNPs could be a promising alternative or adjunctive treatment option for combating antibiotic-resistant P. aeruginosa infections. Further research is warranted to explore the clinical applications of SeNPs in treating biofilm-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 © 2024 Elsevier Ltd. All rights reserved.)

Gallibacterium anatis is a member of the Pasteurellaceae family and is an opportunistic pathogen that causes gallibacteriosis in chickens. Stress plays a relevant role in promoting the development of pathogenicity in G. anatis. Epinephrine (E) and norepinephrine (NE) are relevant to stress; however, their effects on G. anatis have not been elucidated. In this work, we evaluated the effects of E and NE on the growth, biofilm formation, expression of adhesins, and proteases of two G. anatis strains, namely, the hemolytic 12656-12 and the nonhemolytic F149 T biovars. E (10 μM/mL) and NE (30 and 50 μM/mL) increased the growth of G. anatis 12656-12 by 20 % and 25 %, respectively. E did not affect the growth of F149 T , whereas 40 μM/mL NE decreased bacterial growth by 25 %. E and NE at a dose of 30-50 μM/mL upregulated five fibrinogen adhesins in the 12565-12 strain, whereas no effect was observed in the F149 T strain. NE increased proteolytic activity in both strains, whereas E diminished proteolytic activity in the 12656-12 strain. E and NE reduced biofilm formation (30 %) and increased Congo red binding (15 %) in both strains. QseBC is the E and NE two-component detection system most common in bacteria. The qseC gene, which is the E and NE receptor in bacteria, was identified in the genomic DNA of the 12565-12 and F149 T G. anatis strains via PCR amplification. Our results suggest that QseC can detect host changes in E and NE concentrations and that catecholamines can modulate the expression of several virulence factors in G. anatis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Otitis externa is an inflammatory disease of the external ear canal of complex and multifactorial etiology associated with recurrent bacterial infection. This study aimed to assess the antimicrobial and antibiofilm activity of promethazine against bacterial isolates from dogs with otitis externa, as well as the effect of this compound on the dynamics of biofilm formation over 120 h. Planktonic bacterial susceptibility to promethazine was evaluated to determine the minimum inhibitory concentrations (MIC). The minimum biofilm eradication concentration (MBEC) was also determined by broth microdilution. To evaluate the effect on biofilm growth, promethazine was tested at three concentrations MIC, MIC/2 and MIC/8, with daily readings at 48, 72, 96 and 120 h. The MICs of promethazine ranged from 48.83 to 781.25 μg mL -1 . Promethazine significantly (P < 0.05) reduced mature biofilm biomass, with MBECs ranging from 48.8 to 6250 μg mL -1 and reduced (P < 0.01) biofilm formation for up to the 120-h, at concentrations corresponding to the MIC obtained against each isolate. Promethazine was effective against microorganisms associated with canine otitis externa. The data suggest that promethazine presents antimicrobial and antibiofilm activity and is a potential alternative to treat and prevent recurrent bacterial otitis in dogs. These results emphasize the importance of drug repurposing in veterinary otology as an alternative to reduce antimicrobial resistance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Debora Castelo-Branco reports financial support was provided by National Council for Scientific and Technological Development. Jose Sidrim reports financial support was provided by National Council for Scientific and Technological Development. None to declare. If there are other authors, they 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.)

Vibrio cholerae is an inherent inhabitant of aquatic ecosystems. The Indian state of West Bengal, especially the Gangetic delta region is the highest cholera affected region and is considered as the hub of Asiatic cholera. V. cholerae were isolated from publicly accessible wastewater of Midnapore, West Bengal, India. Serotyping determined all isolates to be of non-O1/non-O139 serogroups. Moderate biofilm-forming abilities were noticed in most of the isolates (74.7 %) while, high biofilm formation was recorded for only 6.3 % isolates and 19 % of isolates exhibited low/non-biofilm-forming abilities. PCR-based screening of crucial diguanylate cyclases (DGCs) involved in cyclic-di-GMP-mediated biofilm signaling was performed. cdgH and cdgM were the most abundant DGCs among 93.7 % and 91.5 % of isolates, respectively. Other important DGCs, i.e., cdgK, cdgA, cdgL, and vpvC were present in 84 %, 75.5 %, 72 % and 68 % of isolates, respectively. Besides, the non-O1/non-O139 isolates were screened for the occurrence of virulence factor encoding genes. Moreover, among these non-O1/non-O139 isolates, two strains (3.17 %) harbored both ctxA and ctxB genes, which encode the cholera toxin associated with epidemic cholera. ompU was the most prevalent virulence factor, present in 24.8 % of isolates. Other virulence factors like, zot and st were found in 4.7 % and 9.5 % of isolates. Genes encoding tcp and ace were found to be PCR-negative for the isolates. Additionally, crucial virulence factor regulators, toxT, toxR and hapR were found to be PCR-positive in all the isolates. Antibiotic resistance patterns displayed further vulnerabilities with decreased sensitivity towards commonly used antibiotics with multiple antibiotic resistance index ranging between 0.37 and 0.62. The presence of cholera toxin-encoding multi-drug resistant (MDR) V. cholerae strains in environmental settings is alarming. High occurrence of DGCs are considered to encourage further investigations to use them as alternative therapeutic targets against MDR cholera pathogen due to their unique presence in bacterial systems., 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.)

Multi-drug resistance is recognized as a significant worldwide public health concern in the current century. Biofilm formation further exacerbates bacterial resistance to antibacterial medications, host immunological responses, and phagocytosis, resulting in long-lasting chronic illnesses. Investigating natural resources is a very potent approach for developing alternative anti-infective medications to effectively control multi-drug resistant bacterial infections. In this study, a unique mushroom species namely Pleurotus platypus had been discovered from the Terai-Duars region of West Bengal, India. The myco-chemical profiling and preliminary chemical analysis of Pleurotus platypus methanolic extract determined the significant presence of metabolites belonging to several major chemical classes such as flavonoid, alkaloid, triterpenoid, polyphenol, benzoic acids, coumarin, flavone etc. Most intriguingly, the extract possessed effective antibacterial, antibiofilm and antivirulence properties against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus, one of the most notable drug-resistant opportunistic and nosocomial pathogens. Mechanistically, the mushroom extract enhanced the production of Reactive Oxygen Species (ROS) inside the targeted bacteria, causing alterations in membrane potential, damage to the cellular membrane and further release of intracellular DNA, destined to cell death. Moreover, the methanolic extract reported the eradication of pre-existing biofilms from the urinary catheter surface, hinting towards its future application in the related field. To summarize, Pleurotus platypus methanolic extract could be an excellent alternative antibacterial and antibiofilm therapeutic candidate for the effective management of Staphylococcus infections with improved outcome., 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.)

Objectives: Photodynamic inactivation (PDI) is a powerful technique for eradicating microorganisms, and our group previously demonstrated its effectiveness against planktonic cultures of Staphylococcus aureus bacteria using 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and visible light irradiation. However, biofilms exhibit a lower sensitivity to PDI, mainly due to limited penetration of the photosensitizer (PS). In the context of emerging antibacterial strategies, near-infrared treatments (NIRTs) have shown promise, especially for combating resistant strains. NIRT can act either through photon absorption by water, causing a thermal effect on bacteria, or by specific chromophores without a significant temperature increase. Our objective was to enhance biofilm sensitivity to TAPP-PDI by pretreatment with NIRT. This combined approach aims to disrupt biofilms and increase the efficacy of TAPP-PDI against bacterial biofilms., Materials and Methods: In vitro biofilm models of S. aureus RN6390 were utilized. NIRTs involved a 980 nm laser (continuous mode, 7.5 W/cm 2 , 30 s, totaling 225 J/cm 2 ) post-TAPP exposure to enhance photosensitizer accumulation. Subsequent visible light irradiation at 180 J/cm 2 was employed to perform PDI. Colony-forming unit counts evaluated the synergistic effect on bacterial viability. Scanning electron microscopy visualized the architectural changes in the biofilm structure. TAPP was extracted from bacteria to estimate the impact of NIRT on biofilm penetration., Results: Using in vitro biofilm models, NIRT application following biofilm exposure to TAPP increased PS accumulation per bacteria. Under these conditions, NIRT induced a transient increase in the temperature of PBS to 46.0 ± 2.6°C (ΔT = 21.5°C). Following exposure to visible light, a synergistic effect emerged, yielding a substantial 4.4 ± 0.1-log CFU reduction. In contrast, the PDI and NIRT treatments individually caused a decrease in viability of 0.9 ± 0.1 and 0.8 ± 0.2-log respectively. Interestingly, preheating TAPP-PBS to 46°C had no significant impact on TAPP-PDI efficacy, suggesting the involvement of thermal and nonthermal effects of NIR action. In addition to the enhanced TAPP penetration, NIRT dispersed the biofilms and induced clefts in the biofilm matrix., Conclusion: Our findings suggest that NIR irradiation serves as a complementary treatment to PDI. This combined strategy reduces bacterial numbers at lower PS concentrations than standalone PDI treatment, highlighting its potential as an effective and resource-efficient antibacterial approach., (© 2024 Wiley Periodicals LLC.)

Staphylococcus aureus is widely distributed in environment and can cause various human infection and food poisoning cases. Also, this pathogen is a typical biofilm former, which further complicates its pathogenicity. Antibiotics have been widely used to eliminate pathogenic bacteria, but their indiscriminate use has also led to the widespread emergence of drug-resistant bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA). In this study, the effect of antibiotics on biofilm formation of MRSA strains 875 and 184 was explored. Firstly, MRSA 875 belongs to SCCmec type IV, ST239, carrying the atl, icaA, icaD, icaBC, and aap genes, and MRSA 184 belongs to SCCmec type II, ST5, carrying the atl, icaD, icaBC, aap, and agr genes. Then, a total of 8 antibiotics have been selected, including kanamycin, gentamycin, cipprofloxacin, erythromycin, meropenem, penicillin G, tetracycline, vancomycin. Minimum inhibitory concentrations (MICs) of each antibiotic were determined, and MIC of MRSA 875 and 184 to kanamycin/gentamicin are 2048/64 μg/mL and 2048/4 μg/mL, respectively. A total of 10 concentrations, ranging from 1/128 to 4 MIC with 2-fold, were used to study biofilm formation. Biofilm biomass and viability were determined during different phases, including initial adhesion (8 h), proliferation (16 h), accumulation (24 h) and maturation (48 h). Importantly, kanamycin at specific concentrations showed significant promotion of biofilm biomass and biofilm viability, with none of such observation acquired from other antibiotics. This study provides scientific basis and new research ideas for the quality control technology of microorganisms and safety prevention of MRSA., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biofouling is the undesirable accumulation of living organisms and their metabolites on submerged surfaces. Biofouling begins with adhesion of biomacromolecules and/or microorganisms and can lead to the subsequent formation of biofilms that are predominantly regulated by chemical signals, such as cyclic dinucleotides and quorum-sensing molecules. Biofilms typically release chemical cues that recruit or repel other invertebrate larvae and algal spores. As such, harnessing the biochemical mechanisms involved is a promising avenue for controlling biofouling. Here, we discuss how chemical signaling affects biofilm formation and dispersion in model species. We also examine how this translates to marine biofouling. Both inductive and inhibitory effects of chemical cues from biofilms on macrofouling are also discussed. Finally, we outline promising mitigation strategies by targeting chemical signaling to foster biofilm dispersion or inhibit biofouling., (© 2024. Springer Nature America, Inc.)

In the present study, we investigated the anti-biofilm effect of urinary catheters fabricated with biogenic nanoparticles synthesized from metabolites of Justicia adhatoda under in vitro conditions against human pathogenic bacteria. Silver nanoparticles were synthesized in the reaction mixture composed of 2 % w/v of 0.1 M of precursor (silver nitrate) and 0.2 g of the metabolites obtained from ethanolic extract of Justicia adhatoda. Characterization of the nanoparticles was done by UV visible spectroscopy, fourier infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X ray diffraction (XRD) to confirm the structural and functional properties. Primary conformation of nanoparticles synthesis by UV visible spectroscopy revealed the notable absorption spectra at 425 nm with a wavelength shift around 450 nm, likely due to surface plasmon resonance excitation. SEM analysis showed spherical, monodisperse, nano scale particles with a size range of 50-60 nm. Crystaline phase of the synthesized nanoparticles was confirmed by x ray diffraction studies which showed the distinct peaks at (2θ) 27.90, 32.20, 46.30, 54.40, and 67.40, corresponding to (111), (200), (220), (222), and (311) planes of nano scale silver. The biocompatibility of these nanoparticles was assessed through zebrafish embryonic toxicity study which showed more than 90 % of embryos were alive and healthy. No marked changes on the blood cells also confirmed best hemocompatibility of the nanoparticles. Synthesized nanoparticles thus obtained were fabricated on the urinary catheter and the fabrication was confirmed by FTIR and SEM analysis. Notable changes in the absorption peaks, uniform coating and embedding of silver nanoparticles studied by FTIR and SEM analysis confirmed the fabrication of silver nanoparticles. The coated catheters demonstrated significant antibacterial activity against pathogenic bacterial strains, including E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Anti-biofilm studies, conducted using a modified microtiter plate crystal violet assay, revealed effective inhibition of both bacterial adhesion and biofilm development. 85 % of biofilm inhibition was recorded against both the tested strains. The coating method presented in this study shows promise for enhancing infection resistance in commonly used medical devices like urinary catheters, thus addressing device-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 © 2024 Elsevier Ltd. All rights reserved.)

Biofilm-mediated Salmonella enterica serovar Typhi (Salmonella Ser. Typhi) infections are a growing global health issue due to the formation of antibiotic resistance. The study aimed to discover some of the druggable target proteins of Salmonella Ser. Typhi biofilm and antibiofilm enzyme to prevent Salmonella Ser. Typhi biofilm-mediated infection. Enzymatic therapy has demonstrated effective therapeutic results against bacterial infections due to its specificity and high binding capacity to the target. Therefore, this study focused on the computational interaction between the cellulase enzyme and Salmonella Ser. Typhi biofilm targets proteins with help of the various computational experiments such as ADMET (absorption, distribution, metabolism, excretion, and toxicity), protein-protein interactions, MMGBSA, etc. Further, in vitro validations of the typhoidal biofilm and cellulose presence in Salmonella Ser. Typhi biofilm was conducted using Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy, and Raman analysis. Additionally, a minimum biofilm inhibitory concentration assay for cellulase was conducted and find out the optimized cellulase concentration which showed its inhibitory effect on the Salmonella Ser. Typhi. The cellulase antibiofilm effect was analyzed with the help of SEM analysis. Further, the cellulose content in Salmonella Ser. Typhi was quantified before and after treatment of cellulase enzyme. As a result, 58.82 % cellulose content was decreased due to cellulase treatment in Salmonella Ser. Typhi. From the seven selected typhoidal biofilm regulatory proteins of Salmonella Ser. Typhi, we identified only five potential druggable targets: BcsA, CsgE, OmpR, CsgF, and CsgD. The BcsA protein is responsible for cellulose production in Salmonella Ser. Typhi biofilm. Consequently, cellulose worked as a fascinating drug target in Salmonella Ser. Typhi biofilm. Therefore, we used cellulase as a potential antibiofilm enzyme for target-based disruption of biofilm. The cellulase showed a high binding affinity with all five identified target proteins [BcsA(-205.62 kcal/mol) > CsgE(-108.20 kcal/mol) > OmpR(-107.58 kcal/mol) > CsgF(-73.74 kcal/mol) > CsgD(-66.61 kcal/mol)] in the protein-protein interaction analysis. Our computational analysis suggests that the cellulase enzyme may be used as a potential antibiofilm enzyme against Salmonella Ser. Typhi biofilm., 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.)

Objective: This work aimed to evaluate the in vitro effect of zinc oxide-eugenol paste (ZOE) on planktonic aggregates (EfPA) and biofilm (EfBio) of Enterococcus faecalis, focusing on their morphological aspects observed and analyzed using atomic force microscopy (AFM)., Design: The eugenol and paste were characterized by Gas Chromatography coupled with Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FTIR), respectively. The effect of ZOE on EfPA and EfBio was evaluated by a direct-contact test through colony counting and crystal violet staining protocol. AFM images of untreated and treated EfPA and EfBio growth on bovine dentin were obtained to analyze the morphological damage caused by the treatments., Results: The characterization showed high purity in the eugenol composition and chemical interaction between the components of the paste. A bactericidal effect on aggregates was observed after 6 h of exposure, and on biofilm after 24 h of treatment (p < 0.001). A disruptive effect on the biofilm was also evident. AFM images revealed the formation of EfPA, with a notable presence of an exopolysaccharide matrix. After 6 h of ZOE treatment, there was a significant increase in the size and surface roughness profile of treated cells (p < 0.05). Loss of typical cell morphology was observed after 24 h. The effect on the biofilm showed a tendency towards a less condensed biofilm pattern in the treated group, with no differences in surface roughness., Conclusion: ZOE presents bactericidal action on EfPA and EfBio, promoting significant morphological changes after treatment, especially in the aggregates., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Foodborne pathogens continue to challenge public health due to their ability to cause severe illness and their increasing resistance to current antimicrobial treatments. Listeria monocytogenes is a resilient foodborne pathogen that poses significant risks to vulnerable populations, leading to severe infections and high hospitalization rates. The emergence of antimicrobial-resistant (AMR) strains of L. monocytogenes underscores the need for novel therapeutic strategies. In this study, we investigated the antimicrobial efficacy of the (2E)-3-(3,5-dibromo-2-hydroxylphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (DK06) against multidrug-resistant L. monocytogenes. DK06 exhibited a significant dose-dependent inhibition of L. monocytogenes growth, achieving a maximum inhibition of 92.9 % at 320 μM. Molecular docking and dynamics simulations revealed high binding affinities for key virulence proteins PlcB and ArgA, with stable protein-ligand interactions. DK06 also disrupted biofilm formation at sub-MIC levels, reducing extracellular polymeric substances (EPS) and biofilm mass, as observed by scanning electron microscopy (SEM) analysis. Furthermore, DK06 downregulated the expression of virulence genes (plcB, argA, and hly) and decreased hemolytic activity. In vivo zebrafish studies confirmed the safety of DK06 up to 80 μM, demonstrating its efficacy in reducing mortality and oxidative stress associated with L. monocytogenes infection. DK06 also attenuated inflammation by downregulating key inflammatory markers (tnfa, il1b, il6, and nfkb). These findings indicate that DK06 is a promising multi-target inhibitor with potential application in treating infections and combating antimicrobial 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 © 2024 Elsevier Ltd. All rights reserved.)

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin -12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use., 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.)

With the alarming rise of antibiotic-resistant bacteria, novel antibacterial substances are urgently needed for controlling and treating multidrug-resistant bacterial infections. Edwardsiella piscicida is an important zoonotic enteric pathogen, that can cause systemic hemorrhagic septicemia in fish. Carvacrol, a major terpene of oregano essential oil, has a wide range of antibacterial activities. This study aimed to analyze the effect of carvacrol on the growth and virulence of E. piscicida in vitro. The minimum inhibitory concentration (MIC) of carvacrol against E. piscicida was 125 μg/mL. The sub-inhibitory concentrations of carvacrol significantly decreased the biofilm formation of E. piscicida in a dose dependent manner, whereas increased the hemolytic activity with a negative correlation. The quantitative real-time PCR results showed that carvacrol at sub-MICs downregulated the expression of related virulence genes, including flagellum (fimA, fliC, flgN), hemolysins (ethA, ethB), quorum sensing systems (luxR, qseB), T3SS (esrB, esrC) and T6SS (evpB, evpC). Moreover, carvacrol (≤1/8 MIC) reduced the cytotoxicity, adherence and internalization activities of E. piscicida to the EPC cells. In vivo trial, the diet mixed with carvacrol increased the survival of zebrafish infected with E. piscicida. Overall, these findings suggested that carvacrol might be a promising therapeutic agent against E. piscicida infection in aquaculture., 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.)

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The spread of bacterial resistance has become a significant public health concern, resulting in increased healthcare costs, mortality, and morbidity. Phytochemicals such as Eugenol, the major component of Indian clove and cinnamon essential oils, have attracted attention due to their antimicrobial potential. Thus, this systematic review aims to analyze the existing literature on the antibacterial potential of Eugenol concerning its activity against biofilms, bacterial communication systems (quorum sensing - QS), and associated virulence factors. For this, four databases were systematically searched to retrieve articles published between 2010 and 2023. Fourteen articles were selected based on eligibility criteria and the evaluation of antibacterial activity through minimum inhibitory concentration (MIC) assays, biofilm studies, and assessment of virulence factors. The results revealed that Eugenol has the potential to act as an antimicrobial, antibiofilm, anti-virulence, and anti-QS agent against a variety of bacterial strains associated with chronic, dental, and foodborne infections, including resistant strains, particularly those in the ESKAPE group (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and clinical isolates. Furthermore, Eugenol effectively targets key genes involved in bacterial virulence regulation, biofilm, and QS, as supported by data from multiple assays and research techniques. This review suggests Eugenol's antibacterial activity against biofilm and virulence factors likely stems from its influence on different QS systems. Finally, Eugenol holds promise as a potential candidate for combating resistant bacterial infections, serving as an anti-biofilm agent in medical devices and hospital surfaces, as well as in the food industry, as a toothpaste additive, and as a molecule for the development of new therapeutic agents with the potential to inhibit bacterial virulence, QS systems and avoiding bacterial 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 © 2024 Elsevier Ltd. All rights reserved.)

Medical device-associated infections are a pervasive global healthcare concern, often leading to severe complications. Bacterial biofilms that form on indwelling medical devices, such as catheters, are significant contributors to infections like bloodstream and urinary tract infections. This study addresses the challenge of biofilms on medical devices by introducing a portable antimicrobial catheter insert (PACI) designed to be efficient, biocompatible, and anti-infective. The PACI utilizes nitric oxide (NO), known for its potent antimicrobial properties, to deter bacterial adhesion and biofilm formation. To achieve this, a photoinitiated NO donor, S-nitroso-N-acetylpenicillamine (SNAP), is covalently linked to a polydimethylsiloxane (PDMS) polymer. This design allows for higher NO loading for long-term impact and prevents premature donor leaching, a common challenge with SNAP-blended polymers. The SNAP-PDMS material was applied to a side-glowing fiber optic and connected to a wearable light module emitting 450 nm light, creating a functional antimicrobial insert. Activation of the fiber optic, accomplished with a one-click mechanism, enables real-time NO release, maintaining controlled NO levels for a minimum of 24  hours. The therapeutic levels of NO released via photocatalysis from the PACI demonstrated remarkable efficacy, with >90 % reduction in bacterial viability against S. aureus, S. epidermidis, and P. mirabilis without any cytotoxic impact on mammalian cells. This study underscores the potential of the NO-releasing insert in clinical settings, providing a portable and adaptable solution for preventing catheter-associated infections., Competing Interests: Declaration of competing interest Dr. Elizabeth J. Brisbois is the founder of a startup company involved in exploring the possibility of using nitric oxide-releasing materials for medical applications., (Copyright © 2024. Published by Elsevier B.V.)

Candida auris has emerged as a major multidrug-resistant nosocomial pathogen. The organism exhibits a persistent colonising phenotype, and causes recalcitrant infections often strongly linked to biofilm formation. Alternate strategies are urgently needed to combat this yeast and its biofilm-associated phenotype. This work aimed to evaluate the efficacy of select staphylococcal phenol soluble modulins (PSMs), namely, a truncated version of Staphylococcus aureus PSMα2 shortened by two amino acids at the N-terminal (SaΔ1Δ2PSMα2) and Staphylococcus epidermidis PSMδ against C. auris in vitro and in vivo. The antifungal and antibiofilm activity was tested by broth microdilution and XTT dye reduction assay. Combination effect with antifungal drugs was determined by fractional inhibitory concentration test. The efficacy of combination therapy using SaΔ1Δ2PSMα2 with amphotericin B or caspofungin was evaluated in murine model of C. auris catheter-associated infection. Based on antifungal activity, antibiofilm activity and cytotoxicity data, SaΔ1Δ2PSMα2 exhibited promising activity against C. auris biofilms. Nearly 50 % inhibition in biofilm formation was noted with 0.5-2 μM of the peptide against multiple clinical and C. auris colonizing isolates. It was synergistic with amphotericin B (ΣFIC = 0.281) and caspofungin (ΣFIC = 0.047) in vitro, and improved the activity of voriconazole in voriconazole-resistant C. auris. Combination therapy using amphotericin B or caspofungin (1 μg/ml) with SaΔ1Δ2PSMα2 resulted in 99.5 % reduction in C. auris biofilm in murine model, even when the peptide was used at a concentration that was neither fungicidal nor antibiofilm (0.125 μM; ≈0.26 μg/ml). The study provides insight into the potential utility of SaΔ1Δ2PSMα2-antifungal drug combination against C. auris biofilm-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 © 2024 Elsevier Ltd. All rights reserved.)

Methicillin-Resistant Staphylococcus aureus forming into biofilms can trigger chronic inflammation and disrupt skin wound healing processes. Prolonged and excessive use of antibiotics can expedite the development of resistance, primarily because of their limited ability to penetrate microbial membranes and biofilms, especially antibiotics with intracellular drug targets. Herein, we devise a strategy in which virus-inspired nanoparticles control the release of antibiotics through rapid penetration into both bacterial cells and biofilms, thereby combating antimicrobial-resistant infections and promoting skin wound healing. Lipid-based nanoparticles based on stearamine and cholesterol were designed to mimic viral highly ordered nanostructures. To mimic the arginine-rich fragments in viral protein transduction domains, the primary amines on the surface of the lipid-based nanoparticles were exchanged by guanidine segments. Levofloxacin, an antibiotic that inhibits DNA replication, was chosen as the model drug to be incorporated into nanoparticles. Hyaluronic acid was coated on the surface of nanoparticles acting as a capping agent to achieve bacterial-specific degradation and guanidine explosion in the bacterial microenvironment. Our virus-inspired nanoparticles displayed long-acting antibacterial effects and powerful biofilm elimination to overcome antimicrobial-resistant infections and promote skin wound healing. This work demonstrates the ability of virus-inspired nanoparticles to achieve a dual penetration of microbial cell membranes and biofilm structures to address antimicrobial-resistant infections and trigger skin wound healing., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: We aimed to evaluate the effectiveness of alternating magnetic fields (AMF) combined with antibiotics in reducing Staphylococcus aureus biofilm on metal implants in a large animal model, compared to antibiotics alone., Methods: Metal plates were inoculated with a clinical MRSA strain and then implanted into thirty-three ewes divided into three groups: positive control, linezolid only, and a combination of linezolid and AMF. Animals had either titanium or cobalt-chrome plates and were sacrificed at 5 or 21 days post-implantation. Blood and tissue samples were collected at various time points post-AMF treatment., Results: In vivo efficacy studies demonstrated significant biofilm reduction on titanium and cobalt-chrome implants with AMF-linezolid combination treatment compared to controls. Significant bacterial reductions were also observed in surrounding tissues and bones. Cytokine analysis showed improved inflammatory responses with combination therapy, and histopathology confirmed reduced inflammation, necrosis, and bacterial presence, especially at 5 days post-implantation., Conclusions: This study demonstrates that combining AMF with antibiotics significantly reduces biofilm-associated infections on metal implants in a large animal model. Numerical simulations confirmed targeted heating, and in vivo results showed substantial bacterial load reduction and reduced inflammatory response. These findings support the potential of AMF as a non-invasive treatment for prosthetic joint infections., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.E.G. and R.C. are inventors of the AMF device and are employees and/or consultants for Solenic Medical. D.E.G. and R.C. own stock in Solenic Medical. I.A.S., J.T., and B.P. are employees of Solenic Medical. Remaining authors do not have any competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)