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Chronic periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. The underlying pathogenesis often involves the formation of bacterial biofilm that protects the pathogen from both host immune responses and antibiotics. The gold standard treatment requires implant removal, a procedure that carries associated morbidity and mortality risks. Strategies to preserve the implant while treating PJI are desperately needed. Our group has developed an anti-biofilm treatment, PhotothermAA gel, which has shown complete eradication of 2-week-old mature biofilm in vitro. In this study, we tested the anti-biofilm efficacy and safety of PhotothermAA in vivo when combined with debridement, antibiotics and implant retention (DAIR) in a rabbit model of knee PJI. New Zealand white rabbits (n = 21) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) after capsule closure. At 2 weeks, rabbits underwent sham surgery (n = 6), DAIR (n = 6), or PhotothermAA with DAIR (n = 9) and were sacrificed 2 weeks later to measure implant biofilm burden, soft-tissue infection, and tissue necrosis. The combination of anti-biofilm PhotothermAA with DAIR significantly decreased implant biofilm coverage via scanning electron microscopy compared to DAIR alone (1.8 versus 81.0%; P <.0001). Periprosthetic soft-tissue cultures were significantly decreased in the PhotothermAA with DAIR treatment group (log reduction: Sham 1.6, DAIR 2.0, combination 5.6; P <.0001). Treatment-associated necrosis was absent via gross histology of tissue adjacent to the treatment area (P =.715). The addition of an anti-biofilm solution like PhotothermAA as a supplement to current treatments that allow implant retention may prove useful in PJI treatment. [ABSTRACT FROM AUTHOR]

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G–) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G– bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria. Schematic illustration of TPI-CysHHC10 comprising AMPs and AIE photosensitizer as a photoactivatable, broad-spectrum, antibacterial agent for combating biofilms. [Display omitted] [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are promising alternatives to antibiotics to treat bacterial and fungal infections, especially drug-resistant clinical pathogens. Antimicrobial peptides (AMPs) were synthesized and antimicrobial activity was assayed. The antibacterial mechanism, ATP production, ROS generation and molecular mechanism were determined. Biofilm inhibition assay was performed in planktonic bacterial cells and biofilm degradation assay was performed using mature biofilm. The synthesized AMP2 was subjected to in vitro and in vivo analysis to analyze the safety. The synthesized peptides AMP1, AMP2, AMP3 and AMP4 exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria. The MIC values ranged from 1.5 ± 0.25–12.5 ± 1.25 µM and the MFC values range from 2.25 ± 0.12–25 ± 1.25 µM. F. solani showed fewer MFC values than other fungal strains. Time kill assay was performed and the AMP2 killed about 70 % of Acinetobacter baumannii at 1 × MIC concentration within 10 min incubation and killed 97 % of bacteria at 1 × MBC concentration within 15 min. The antimicrobial peptide AMP2 was highly effective against planktonic A. baumannii and L. monocytogenes. The tested AMP2 showed less toxicity to cell lines and Zebrafish. Antimicrobial peptides have potential antimicrobial properties against Gram-positive and Gram-negative bacteria. The in silico studies of these antimicrobial peptides are useful for eradicating drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

• Multidrug resistance in important food pathogens abounds. • Antimicrobial potential of extracts of Loxostylis alata was explored. • L. alata reduced bacterial cell attachment and biofilm biomass. • Anti-biofilm activity is an alternative mechanism to overcome bacterial infection. Bacterial biofilms pose health challenges both in clinical environments and the food industry. Major foodborne bacterial pathogens form biofilms on surfaces and persist, causing infections in humans that may be difficult to treat. Conventional use of antibiotics is fast becoming ineffective due to emerging resistance of pathogens to antibiotics. Previous studies have demonstrated the antimicrobial potential of Loxostylis alata A. Spreng. ex Rchb. extracts against a range of bacterial pathogens. The inhibitory effects of methanol and aqueous extracts of L. alata and an antibacterial compound (5-demethyl sinensetin) isolated from the leaves on the growth and development of microbial biofilms was investigated against clinical isolates of Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and reference strains of Bacillus cereus, Salmonella Enteritidis and Salmonella Typhimurium using the crystal violet (CV) assay. The Kirby-Bauer disk diffusion method was utilized to determine antibiotic susceptibility and resistance profiles of the four clinical and three reference isolates. E. cloacae was resistant to tetracycline and doxycycline and P. mirabilis was resistant to colistin while E. coli and K. pneumoniae were pan-susceptible to all the antibiotics screened. The hot water extract reduced biofilm adhesion from 7% to >50% for the clinical isolates and the ATCC strains, except for S. Typhimurium. The methanol extract inhibited the growth of preformed biofilms of S. Enteritidis and S. Typhimurium by >50% and also reduced the biofilm biomass in S. Enteritidis and E. coli by >50%. The plant extracts and compound were able to reduce initial cell attachment and biofilm biomass, although inhibition of growth in a preformed biofilm was not attained. [ABSTRACT FROM AUTHOR]

In the present study, the antibacterial and anti-biofilm activity of selenium nanoparticles (SeNPs) produced by Bacillus subtilis BSN313 was investigated. Agar diffusion and microdilution methods did not reveal significant antibacterial activity of SeNPs against P. aeruginosa ATCC 9027, S. typhi ATCC 14028, and S. aureus ATCC 25923 due to the larger size of SeNPs and higher electrophoretic mobility, zeta potential, and/or poor diffusion properties in agar solids. Therefore, the agar overlay method was introduced, and significant antibacterial activity was observed with this method at concentrations (SeNPs) of 200 µg/mL, 150 µg/mL, and 150 µg/mL against P. aeruginosa ATCC 9027, S. typhi ATCC 14028, and S. aureus ATCC 25923, respectively. Atomic force spectroscopy (AFM) results, elucidated the disintegrating effect of SeNPs against Gram-negative (P. aeruginosa ATCC 9027) and Gram-positive (S. aureus ATCC 25923) pathogens. The disintegrating effect of SeNPs was caused by the destruction of the bacterial cell (biofilm producing) by rupturing the cell membrane. The hydrophobicity and zeta potential of the planktonic and biofilm populations were measured. Higher values of hydrophobicity and zeta potential heterogeneity were found for the biofilm population than for the planktonic population. The SeNPs showed significant anti-biofilm activity against biofilm-producing pathogenic strains. The ability of SeNPs to disperse biofilms was greatest at a concentration of 700 µg/mL within 15 min against P. aeruginosa ATCC 9027 (85.7%), S. typhi ATCC 14028 (89.6%), and S. aureus ATCC 25923 (78.3%). While the positive control (ascorbic acid, 32 µg/mL) showed an average dispersion of 95.1% against the biofilms of the strains studied within 90 min. Based on these results, we propose SeNPs as suitable candidates for the treatment of biofilm-producing pathogens. [Display omitted] • Antibacterial and anti-biofilm activities of selenium nanoparticles produced by Bacillus subtilis BSN313. • Agar overlay method, was used for significant antibacterial activity. • Atomic force spectroscopy, elucidated the disintegrative effect of SeNPs against bacteria. • Higher zeta potential values were recorded in biofilm populations as compared to planktonic. • Biogenic SeNPs can be recommended against biofilm producing pathogens in therapeutic and food industries. [ABSTRACT FROM AUTHOR]

• Selected plant extracts had activity against MDR Staphylococcus aureus mastitis isolates. • Kalanchoe gunniae was antibacterial with low cytotoxicity (selectivity index 25). • K. gunniae inhibited biofilm development but could not eradicate pre-formed biofilm. • K. gunniae had anti-quorum sensing activity and is a candidate for future studies. Mastitis is a painful inflammatory condition, commonly resulting from infections caused by Staphylococcus aureus and other pathogens. In this study, antimicrobial, anti-biofilm and anti-quorum sensing activities of selected plants were investigated against Staphylococcus aureus isolates from clinical cases of bovine mastitis. Acetone and ethanol extracts of 15 plants were initially screened for their antimicrobial activities against the commercially available reference strain S. aureus ATCC 29213. Maytenus undata, Maurocenia frangula, Kalanchoe gunniae and Bryophyllum pinnatum had good activities and extracts were tested against six multi-drug resistant S. aureus strains isolated from clinical bovine mastitis cases. The four plants were further analysed for cytotoxicity and anti-quorum sensing activities. Two of the plants with good results were assessed further for anti-biofilm activity. Minimum inhibitory concentration (MIC) values of the extracts against S. aureus isolates ranged from 0.02 to 0.63 mg/mL. Kalanchoe gunniae extracts were the least cytotoxic with extremely promising selectivity index (SI) values ranging from 12 to 25. Significant inhibition of biofilm development against S. aureus mastitis isolates was observed, but extracts were not able to eradicate pre-formed biofilms. Kalanchoe gunniae extracts had the best anti-quorum sensing activity with minimum quorum sensing inhibition concentration (MQSIC) and MIC values of 0.04 mg/mL and 0.63 mg/mL respectively against Chromobacterium violaceum ATCC 12472. Therefore, K. gunniae holds potential for development of a preventative treatment against bovine mastitis. [ABSTRACT FROM AUTHOR]

X-ray, anti-biofilm, DNA cytotoxicity, computational chemistry and molecular docking studies of o-vanillin Schiff base derivative and its copper complex. [Display omitted] A novel Schiff base derivative, (E)-N'-(2-hydroxy-3-methoxybenzylidene)-2-phenylacetohydrazide (HMPH, H 2 L), and its Cu(II) complex were synthesized through the direct condensation of o-vanillin with phenylacetichydrazide in ethanol under reflux conditions. The synthesized ligand was identified using elemental analysis, Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis.) spectroscopy. The structures of HMPH (C 16 H 16 N 2 O 3) 2 and its Cu(II) complex [Cu(L)(H 2 O)] · H 2 O (C 16 H 16 N 2 CuO 4 ·H 2 O) were analysed by single crystal X-ray diffraction technique. The X-ray diffraction results showed that HMPH crystallised in an orthorhombic Pca 2 1 space group with a Z value of 8, while [Cu(L)(H 2 O)] · H 2 O crystallised in a monoclinic C 2/c space group with the same z value. The Cu(II) ion is coordinated to the acetohydrazide ligands via hydrazone nitrogen, aceto oxygen (N(2) and O(1)) and hydroxyl O(2) atoms. In addition to the single crystal structures of HMPH and [Cu(L)(H 2 O)] · H 2 O , the optimised molecular structures, molecular electrostatic potential meps, molecular orbital energy values, and interactions between DNA bases and molecular structures are determined by DFT/B3LYP/6-311G(d, p) for HMPH and DFT/B3LYP/LanL2DZ for [Cu(L)(H 2 O)] · H 2 O. The copper complex was found to be more potent than the organic ligand in terms of antimicrobial activity, with a strong anti-biofilm effect even at low MIC values. The cytotoxicity of the synthesized compounds was investigated on MDA-MB-231 cell lines. The [Cu(L)(H 2 O)] · H 2 O complex was found to be more lethal than the HMPH ligand. Furthermore, molecular docking studies of HMPH and [Cu(L)(H 2 O)] · H 2 O with P. aeruginosa ATCC27853 (PDB ID: 6P8U) were presented to explain the observed antibacterial activity and the mechanism-of-action. [ABSTRACT FROM AUTHOR]

Vibrio parahaemolyticus can enhance bacterial resistance to disinfectants and antimicrobials by forming biofilms. The development of new natural antimicrobials is essential for the control of biofilm-related contamination and infection. In this paper, we preliminarily explored the inhibitory activity of Sargassum muticum extracts (HA-PTs) against the biofilm of V. parahaemolyticus. HA-PTs exerted anti-biofilm activity by destroying the integrity of the cell membrane, curbing the motility of single and colonial bacteria, hindering the synthesis of polysaccharide intercellular adhesion, inhibiting the secretion of extracellular DNA, and reducing the metabolic activity of biofilms. Furthermore, experiments on four free radicals (DPPH•, •OH, ABTS+•, and O 2 −•) scavenging activity and total antioxidant capacity (FRAP method and phenanthroline method) demonstrated that HA-PTs have strong reducing properties and can capture a variety of free radicals, which in turn prevents them from participating in oxidative reactions. When HA-PTs were applied to Chinese shrimp infected with V. parahaemolyticus , it could prolong their shelf life by controlling the pH rise caused by protein degradation, inhibiting the bacterial proliferation, reducing the content of total volatile basic nitrogen produced by protein degradation, and reducing the accumulation of thiobarbiturates caused by oxidative deterioration of fats. • It is the first report to analyze the anti-biofilm mechanism of HA-PTs against V.P. • HA-PTs can affect the cell membrane integrity and normal physiological activities. • HA-PTs have great free radical scavenging activity and total antioxidant capacity. • HA-PTs can extend the shelf life of infected shrimp from less than 2 days–6 days. [ABSTRACT FROM AUTHOR]

A novel strategy that has emerged in recent years involves the use of aerogels for anti-inflammatory treatment, which has been extensively studied for its powerful application prospects in wound healing, diabetic complications, and tissue regeneration. However, the therapeutic efficacy of aerogels alone is compromised due to bacterial infections at the wound site. Therefore, it is necessary to incorporate effective antibacterial systems onto the aerogels to enhance their efficacy against bacterial infections. For instance, the design of cascade reactions targeting specific disease biomarkers for diagnostic and therapeutic purposes holds promise for enhancing treatment efficacy and precision. In this study, we successfully achieved the immobilization of glucose oxidase within an aerogel prepared from nanozymes, demonstrating remarkable catalytic activity and high-temperature stability. The cascade catalytic system comprising nanozymes and glucose oxidase was applied to combat Methicillin-resistant Staphylococcus aureus (MASR) bacterial infections, exhibiting effective biofilm removal capabilities. In therapeutic experiments on ulcerated wounds in diabetic mice, the cascade catalytic system demonstrated outstanding efficacy with excellent biocompatibility. The therapeutic effects were primarily manifested in the rapid clearance of biofilms formed by MASR, achieved by locally depleting glucose in the wound area, thereby promoting the healing process of ulcerated wounds. [ABSTRACT FROM AUTHOR]

Wild plants provide important bioactive compounds, and their analysis relies heavily on selecting the right extraction techniques and solvents. This study was conducted to determine the phenolic content and biopharmaceutical potential of four different extracts (ethyl acetate, ethanol, 70% ethanol, and water) from the aerial parts of wild plant Tordylium apulum L. The biochemical profile of the extract was screened using high performance liquid chromatography -mass spectrometry (HPLC-MS) analysis. The total phenolic and flavonoid content was examined using the Folin-Ciocalteu assay and the aluminium trichloride assay, respectively. The antioxidant activity was evaluated through several tests, including 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum (PBD), and metal chelating activity (MCA). Five types of enzyme inhibition activity were tested against acetylcholinesterase (AChE), butrylcholinesterase (BChE), tyrosinase, α- amylase, and α -glucosidase. Additionally, For the first time, the inhibitory activity of T. apulum extract against human carbonic anhydrase isoenzymes I and II (hCA-I and hCA-II) was evaluated. Fifty-five compounds for negative ionization mode, and twenty-eight compounds for positive ionization mode were recorded in HPLC-MS analysis and they were polyphenolic, flavonoids, carbohydrates, sugar alcohol and amino acids. These results indicate that different solvents extract varying levels of antioxidants from T. apulum , with ethanol and water extracts generally exhibiting superior antioxidant activities. The ethanol extract of T. apulum exhibited the maximum contents of total phenolics measuring 33.71 mg gallic acid equivalent (GAE)/g. The ethanol extract exhibited the highest inhibition of AChE with 2.28 mg galanthamine equivalent (GALAE)/g. The ethyl acetate and ethanol extracts also showed the highest hCA-I and hCA-II inhibition potential, respectively. The ethanol-water and water extracts acted on the biofilm of E. coli (49.93% and 45.22%, respectively), and the biofilm of P. aeruginosa (50.68% and 44.46%, respectively). The extracts were tested on different cell lines for cytotoxic potentials and in particular the water extract induced the apoptotic pathways in cervical cancer (HELA) cell lines. In conclusion, T. apulum exhibit multidirectional biological properties and it could be considered as a versatile agent for the development of health-promoting applications. [ABSTRACT FROM AUTHOR]

In recent years, photodynamic therapy (PDT) or chemodynamic therapy (CDT) based on the antimicrobial property or anti-biofilm property of reactive oxygen species (ROS) have been widely recognized for their low susceptibility to microbial resistance. However, due to the complication of the three-dimensional structure of the biofilm at the wound site and the high quenching rate of common ROS, the treatment with traditional ROS could not achieve satisfactory wound healing effects. Here, Na 2 S 2 O 8 @ZIF-67/GOx nanoparticles (NZG NPs) were prepared as a new high-toxic ROS nanogenerator for application of biofilm-infecting wound healing with the assistance of glucose oxidase (GOx) for amplified CDT and immune activation. When the NZG NPs entered the biofilm, Co-based metal organic frame (ZIF-67) ruptured in the acidic microenvironment, which induced the release of GOx and the production of gluconic acid and H 2 O 2 , further promoting the decrease of pH of the biofilm microenvironment and in turn accelerating the cleavage of ZIF-67 and the release of Na 2 S 2 O 8. Then, S 2 O 8 2− could gradually transformed into high-toxic sulfate radical (SO 4 −), part of which further produced OH in situ with H 2 O, thereby inhibiting the proliferation of bacteria and biofilms. Interestingly, these two types of ROS not only caused direct damage to the biofilm, but also activated the immune system of the wound site as well as the body more effectively, which also played an indirect role in promoting biofilm destruction and wound healing. In vitro and in vivo results showed that, as a new high-toxic ROS nanogenerator, the NZG NPs supply amplified chemodynamic therapy and immune activation to destroy biofilms, but also achieve effective wound healing without causing bacterial tolerance, which provides a new strategy for the development of biofilm-infecting wound healing. Na 2 S 2 O 8 @ZIF-67/GOx nanoparticles (NZG NPs) were prepared as a new high-toxic ROS nanogenerator for application of biofilm-infecting wound healing through combination of amplified CDT and immune activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Carvacrol is a natural low-cost compound derived from oregano which presents anti-bacterial properties against both Gram-positive and Gram-negative bacteria. In this work, carvacrol-loaded PLA scaffolds were fabricated by 3D printing as platforms to support bone tissue regeneration while preventing biofilm development. Scaffolds were printed with or without a perimeter (lateral wall) mimicking the cortical structure of bone tissue to further evaluate if the lateral interconnectivity could affect the biological or antimicrobial properties of the scaffolds. Carvacrol incorporation was performed by loading either the PLA filament prior to 3D printing or the already printed PLA scaffold. The loading method determined carvacrol localization in the scaffolds and its release profile. Biphasic profiles were recorded in all cases, but scaffolds loaded post-printed released carvacrol much faster, with 50–80% released in the first day, compared to those containing carvacrol in PLA filament before printing which sustained the release for several weeks. The presence or absence of the perimeter did not affect the release rate, but total amount released. Tissue integration and vascularization of carvacrol-loaded scaffolds were evaluated in a chorioallantoic membrane model (CAM) using a novel quantitative micro-computed tomography (micro-CT) analysis approach. The obtained results confirmed the CAM tissue ingrowth and new vessel formation within the porous structure of the scaffolds after 7 days of incubation, without leading to hemorrhagic or cytotoxic effects. The absence of lateral wall facilitated lateral integration of the scaffolds in the host tissue, although increased the anisotropy of the mechanical properties. Scaffolds loaded with carvacrol post-printing showed antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa as observed in a decrease in CFU counting after biofilm detachment, changes in metabolic heat measured by calorimetry, and increased contact killing efficiency. In summary, this work demonstrated the feasibility of tuning carvacrol release rate and the amount released from PLA scaffolds to achieve antibiofilm protection without altering angiogenesis, which was mostly dependent on the perimeter density of the scaffolds. [Display omitted] [ABSTRACT FROM AUTHOR]

The current study aimed to screen bacteriocin producing LAB from different dairy products and evaluation of their biological properties. Initially, 12 (4-chess, 4-curd, and 4-yohurt) LAB species were isolated and only 4 isolates alone were selected based on their clear yellow halo zone around the colonies in the selective medium. The selected 4 isolates were identified based on their morphological and biochemical characteristics. Among them, the strain CH3 have showed better antimicrobial effects on selected human pathogens. The isolated strain CH3 were further identified as Lactococcus lactis strain CH3 (MZ636710) by SEM imaging and 16 s rRNA molecular sequencing. Bacteriocin was extracted from L. lactis strain CH3 and partially purified using 60 % ammonium sulphate and then completely purified by G-50 column chromatography. The purified bacteriocin showed a specific activity of 5859.37 AU/mg in 24.7 % of recovery and 10.9-fold purification. The molecular weight of bacteriocin was 3.5 kDa as observed in SDS-PAGE. The bacteriocin showed sensitivity to proteolytic enzymes and resistance to high temperature, wide range of pH, organic solvents and detergents. FT-IR spectral studies of bacteriocin detected the existence of OH/NH-stretching, CH, and C O C and C O bonds. NMR spectrum showed one doublet and 4 various singlet peaks at different ppm, indicating the occurrence of six amino acids in the structure of purified bacteriocin. The purified bacteriocin have shown stronger antimicrobial and anti-biofilm activity against selected human pathogens at 100 μg/mL. SEM showed the evidence of structural deformation and loss of membrane integrity of bacterial cells treated with bacteriocin. Bacteriocin exhibited greater DPPH radical scavenging potential with an EC 50 value of 12.5 μg/mL. Bacteriocin have not shown significant toxicity on normal human dermal fibroblast (NHDF) cells (83.2 % at 100 μg/ mL). Furthermore, in silico studies using molecular modeling and docking were performed to know the proteins involved in antimicrobial action. The results suggests that bacteriocin could be an alternative to combat AMR pathogens and more suitable for food and dairy industries to preserve food without contamination. • Isolated and identified bacteriocin producing Lactococcus lactis strain CH3. • Structural characterization of bacteriocin were done by FTIR, NMR, and SDS-PAGE. • Bacteriocin have exhibited significant antimicrobial, anti-biofilm and DPPH radical scavenging effects. • Bacteriocin have shown no toxicity on NHDF cells. • In silico studies confirmed that bacteriocin had greater biological properties. [ABSTRACT FROM AUTHOR]

Biofilm formation on biological and material surfaces represents a heavy health and economic burden for both patient and society. To contrast this phenomenon, medical devices combining antibacterial and pro-wound healing abilities are a promising strategy. In the present work, Xanthan gum/Guar gum (XG/GG)-based scaffolds were tuned with thymol and Zn2+ to obtain wound dressings that combine antibacterial and antibiofilm properties and favour the healing process. The tuning process preserved the 3D extrusion-based printability of the XG/GG ink. Scaffolds swelling profile was assessed in PBS pH 7.4, and the resistance to compressive forces was studied using a texturometer. The scaffolds microarchitectures were analyzed by SEM, while ATR-FTIR spotlighted the chemical modifications of the customized materials. Thymol and Zn2+ release was analyzed in biologically relevant media, showing a burst release in the first hours. The antibacterial properties were confirmed against S. aureus , P. aeruginosa , and S. epidermidis by isothermal microcalorimetry and biofilm viable cell counting. Incorporation of hydroxypropyl-β-cyclodextrin (HPβCD) improved thymol loading (7- and 14-times higher thymol content) and enhanced the antimicrobial and antioxidant performances of the dressing, while the presence of Zn2+ strongly potentiated the antimicrobial activity, showing a potent antibiofilm response in both Gram-positive and Gram-negative strains of clinical concern. The thymol and Zn2+ combination led to a reduction of 99.95 %, 99.99 %, and 98.26 %, of biofilm formation against S. aureus , P. aeruginosa , and S. epidermidis , respectively. Furthermore, the scaffolds demonstrated good hemocompatibility, cytocompatibility, tissue integration and pro-angiogenic features in an in ovo CAM model. [ABSTRACT FROM AUTHOR]

Dental biofilms, impacting around 80% of the global population, are a significant issue causing serious dental disorders like periodontitis, which has links to autoimmune diseases such as rheumatoid arthritis. Traditional biofilm management methods, including mechanical removal and chemical agents, often fail to completely eradicate biofilms, allowing oral infections to persist. Nanotechnology offers innovative solutions for medication delivery and biofilm disruption, presenting new opportunities for antimicrobial surfaces and healthcare equipment development. This paper explores advancements in nanotechnology-based strategies to combat dental biofilms, primarily formed by Lactobacillus species, Actinomyces species, and Streptococcus mutans , and examines the composition and characteristics of dental biofilms. The green synthesis of nanoparticles using plant-based ingredients demonstrates significant antibacterial activity against biofilm-associated pathogens. Additionally, the paper investigates the potential of various metal oxide-based nanoparticles, such as titanium, zinc, and silver, in dental treatments to inhibit biofilm formation and enhance oral health. The stages of dental biofilm formation are outlined, highlighting the risks of untreated biofilms, including systemic health implications. This review underscores the promise of nanodrugs in preventing dental biofilms and improving the efficacy of dental procedures. It delves into cutting-edge nanotechnological approaches, emphasizing the novel use of nanoparticles like gold, silver, and antimicrobial peptides, and their unique mechanisms for disrupting biofilm formation and enhancing dental treatments. The review also covers recent advancements in nanotechnology, offering innovative and more effective solutions for targeted dental care strategies, potentially revolutionizing the approach to managing dental biofilms and promoting better oral health outcomes. [Display omitted] • Nanotechnology offers innovative drug delivery system for targeted and controlled release of antimicrobials in the oral cavity. • Green synthesis nanoparticles prepared in the budget friendly way. • Optimized drug delivery systems and conducted clinical trials validated the efficacy and safety of these nanodrug approaches in dental care. [ABSTRACT FROM AUTHOR]

• The hydroethanolic stem bark extract of Treculia africana Decne showed. • Moderate antibacterial activity. • Substantial efflux pump and biofilm inhibitory effects. • Synergistic and additive effects with standard antibiotics. Antimicrobial resistance (AMR) poses a serious threat to humans in all countries of the world. This study investigated the antibacterial, anti-biofilm formation, efflux pump inhibition and resistance modulatory effects of hydroethanolic stem bark extract of Treculia africana Decne (Moraceae) so as to assess its usefulness in the fight against drug-resistant pathogens. Preliminary phytochemical screening of Treculia africana stem bark extract (TASBE) revealed the presence of saponins, glycosides, tannins, triterpenoids and coumarins. The TASBE demonstrated moderate antibacterial activity (MIC = 125 – 500 µg/mL) towards Gram-negative bacteria whilst it showed no activity (MIC > 500 µg/mL) against Gram-positive bacterial species at the highest dose used (500 µg/mL). The extract also exhibited effects against two mycobacterial species, M. aurum (MIC = 500 µg/mL) and M. smegmatis (MIC > 500 µg/mL). Furthermore, the extract exerted potent anti-biofilm formation activity in both M. aurum and M. smegmatis with percentage biofilm inhibition of 56.70 70 ± ± 2.31 % and 59.10 10 ± ± 2.89 % respectively. Additionally, substantial efflux pump inhibitory effects were demonstrated in both M. aurum and M. smegmatis. A combination of the extract with ciprofloxacin exhibited synergistic effect against P. aeruginosa and P. mirabilis and additive effect against E. coli whilst their effect on K. pneumoniae was indifferent. Similarly, TASBE with rifampicin exhibited synergistic activity towards M. smegmatis whilst the effect towards M. aurum was indifferent. This study provides data that could be used to support the traditional use of T. africana in treating gastrointestinal and respiratory tract infections and demonstrates the potential of the extract as a source of novel compounds for tackling antimicrobial resistance. [ABSTRACT FROM AUTHOR]

[Display omitted] Although inhalation powder aerosols of antibiotics have been used to treat respiratory infections caused by Pseudomonas aeruginosa, biofilms are difficult to clear. Ciprofloxacin and D-amino acids (D-Met, D-Trp and D-Phe) were shown to facilitate P. aeruginosa biofilm removal. Spray dried powders for inhalation tend to be amorphous, hence unstable to moisture which causes deterioration in the aerosol performance. Hydrophobic L-amino acids such as leucine can impart moisture protection. In this study, we hypothesized that co-spray dried formulations of ciprofloxacin and hydrophobic D-amino acids will offer the combined benefits of both anti-biofilm and moisture protection properties. Of the three D-amino acids tested, D-Met and D-Trp (at 5 mM) but not D-Phe reduced clinical isolate P. aeruginosa biofilm loads and the extent of biofilm clearance was further enhanced in the presence of ciprofloxacin. Subsequently, ciprofloxacin was spray dried alone or in combination with 30% (w/w) D-Met or D-Trp. The biological and physicochemical properties of the powders were assessed, including the minimum inhibitory concentration, anti-biofilm activity, particle size distribution and morphology, solid-state properties, water sorption, and aerosol performance. The spray dried combination powders were physically stable and inhalable with fine particle fraction (<5 µm) values of 50–57% when aerosolized. The powders exhibited enhanced anti-biofilm activity compared with ciprofloxacin alone. The presence of D-amino acids provided moisture protection, with the recrystallization event shifting from 50% RH to 80% RH in powders containing D-Trp. In conclusion, the use of D-amino acids (D-Met or D-Trp) is an attractive formulation strategy which offers dual benefits of anti-biofilm effect and moisture protection. [ABSTRACT FROM AUTHOR]

A common reason for dental composite restoration failure is recurrent caries at the margins. Our objectives were to: (1) develop a novel low-shrinkage-stress, antibacterial and remineralizing resin composite; (2) evaluate the effects of dimethylaminohexadecyl methacrylate (DMAHDM) on mechanical properties, biofilm inhibition, calcium (Ca) and phosphate (P) ion release, degree of conversion, and shrinkage stress on the new low-shrinkage-stress resin composite for the first time. The resin consisted of urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE) with high resistance to salivary hydrolytic degradation. Composites were made with 0%–8% of DMAHDM for antibacterial activity, and 20% of nanoparticles of amorphous calcium phosphate (NACP) for remineralization. Mechanical properties and Streptococcus mutans biofilm growth on composites were assessed. Ca and P ion releases, degree of conversion and shrinkage stress were evaluated. Adding 2–5% DMAHDM and 20% NACP into the low-shrinkage-stress composite did not compromise the mechanical properties (p > 0.05). The incorporation of DMAHDM greatly reduced S. mutans biofilm colony-forming units by 2–5 log and lactic acid production by 7 folds, compared to a commercial composite (p < 0.05). Adding 5% DMAHDM did not compromise the Ca and P ion release. The low-shrinkage-stress composite maintained a high degree of conversion of approximately 70%, while reducing the shrinkage stress by 37%, compared to a commercial control (p < 0.05). The bioactive low-shrinkage-stress composite reduced the polymerization shrinkage stress, without compromising other properties. Increasing the DMAHDM content increased the antibacterial effect in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Infections on the wound surface are the major problem in restricting the healing process. To reduce the transmission and treat the infection, we have developed 0.05% and 0.1% octenidine dihydrochloride (Ocd) incorporated chitosan (Cs) based flexible bandages. Ocd is extensively used skin antiseptic for its mode of action over a broad spectrum of antimicrobial activity. The prepared antiseptic Cs-Ocd bandage was characterized using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). In addition, swelling, degradation, cytocompability, antibacterial, and anti-biofilm property of the developed bandages were studied. This highly porous nature of Cs-Ocd bandage showed enhanced swelling property, slow degradation profile and controlled release of Ocd. The prepared antiseptic bandage exhibited synergistic effect showing good hemostatic potential with Cs, excellent antimicrobial and anti-biofilm activity with Ocd against Staphylococcus aureus (S. aureus) and Candida auris (C. auris). Thus, the developed Cs-Ocd bandage can be used as potential antiseptic bandage for skin infections. [ABSTRACT FROM AUTHOR]

The utilization of medicinal plants and their drugs have the advantage of reducing side effects compared with manufactured antimicrobials. Artificial drugs have unpleasant side effects, further, the number of drug resistant pathogens is increasing, thus huge challenge for control of resistant pathogens. Therefore, the current research explores the potential of partially purified bioactive compounds from Dodonaea viscosa against certain human pathogens. Healthy leaves of D. viscosa (L.) were collected, extracted and optimized with different solvents. Preliminary phytochemical screening of the extracts was done and antibacterial activities were tested against human pathogens. The active crude extract was further purified by column chromatography and the homogeneity was confirmed by thin layer chromatography (TLC). The partially purified compounds were screened further for antibacterial, antibiofilm and anticancer activities. The crude ethanol extract of D. viscosa leaves showed the presence of phytochemical like tannins, alkaloids, flavanoids, terpenoids, glycosides, steroids and phenols. Ethanol extract exhibited the maximum zone of inhibition (11 mm) against S. agalactiae , B. cereus , S. typhi and E. coli at 15 mg when compared with other bacteria. Column chromatography fractions Dv12 and Dv20 exhibited the maximum zone of inhibition against B. cereus. 1000 μg of Dv12 partially purified compound against streptococcus isolates in glass test tube showed biofilm inhibition range of 34.4%–63.1%. Whereas B. cereus, S. aureus, S. typhi , and K. pneumoniae showed 31.1%–53.6% biofilm inhibition compared to curcumin control. Active fractions of Dv12 and Dv20 increased concentration confirmed that the gradual decrease in cell density and possesses growth inhibition towards A 549 human lung adenocarcinoma cells. We have extracted the bioactive compounds from D. viscosa (L.) leaves and tested the activity of a partially purified compound against human pathogenic bacteria, biofilm formation and cytotoxicity against A 549 human lung adenocarcinoma cells. The purified bioactive compounds might be used as therapeutic agents against different microbial infections such as skin infection, throat infection and other infectious diseases. [ABSTRACT FROM AUTHOR]

Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound site, hydrogels can lose their structural and functional integrity. To overcome this and to effectively seal the wound and control infection, an in-situ silver nanoparticles (AgNps) incorporated N , O -carboxymethyl chitosan (N , O -CMC) based self-healing hydrogel using ethylenediaminetetraacetic acid-ferric ion (EDTA: Fe3+) complex was developed. The prepared N , O -CMC/AgNps hydrogel was characterized using FTIR, SEM, and TEM. The developed N , O -CMC/AgNps hydrogel was found to be adhesive, injectable, conductive, bio-compatible, and showed antibacterial activity against ATCC and clinical strains of E. coli , K. pneumonia , P. aeruginosa , S. aureus and MRSA. N , O -CMC/AgNps hydrogel also showed anti-biofilm activity against S. aureus , E. coli , and P. aeruginosa (ATCC strains). This developed antibacterial and self-healing N , O -CMC/AgNps hydrogel can be used in the treatment of infected wounds. [ABSTRACT FROM AUTHOR]

Chronic infections caused by the pathogenic biofilms on implantable medical devices pose an increasing challenge. To combat long-term biofilm-associated infections, we developed a novel dual-functional polymer coating with antibacterial and antifouling properties. The coating consists of N-vinylpyrrolidone (NVP) and 3-(acrylamido)phenylboronic acid (APBA) copolymer brushes, which bind to curcumin (Cur) as antibacterial molecules through acid-responsive boronate ester bonds. In this surface design, the hydrophilic poly (N-vinylpyrrolidone) (PVP) component improved antifouling performance and effectively prevented bacterial adhesion and aggregation during the initial phases. The poly (3-(acrylamido) phenylboronic acid) (PAPBA, abbreviated PB) component provided binding sites for Cur by forming acid-responsive boronate ester bonds. When fewer bacteria overcame the anti-adhesion barrier and colonized, the surface responded to the decreased microenvironmental pH by breaking the boronate ester bonds and releasing curcumin. This responsive mechanism enabled Cur to interfere with biofilm formation and provide a multilayer anti-biofilm protection system. The coating showed excellent antibacterial properties against Escherichia coli and Staphylococcus aureus , preventing biofilm formation for up to 7 days. The coating also inhibited protein adsorption and platelet adhesion significantly. This coating also exhibited high biocompatibility with animal erythrocytes and pre-osteoblasts. This research offers a promising approach for developing novel smart anti-biofilm coating materials. [Display omitted] • An acid-responsive curcumin macromolecular polymer coating was developed. • Curcumin and poly (NVP-co-APBA) brushes were linked by dynamic covalent bond. • The coating exhibited excellent antibacterial and anti-biofilm ability. • The coating reduced protein and platelet adhesion with high biocompatibility. • The coating provided a smart anti-biofilm protection system for implantable devices. [ABSTRACT FROM AUTHOR]

Microbial infections are considered common and dangerous for humans among other infections; therefore the synthesis of high efficacy antimicrobial and anti-biofilm composites is continuous to fight microbial resistance. In our study, a new and novel tertiary composite (TC) was synthesized, it composed of TEMPO cellulose (TOC), chitosan, starch, and myco-synthesized Se-NPs. Myco-synthesized Se-NPs and TC were fully characterized using UV, FT-IR, XRD, SEM with EDX, particle distribution, and mapping. The antimicrobial and anti-biofilm properties of selenium nanoparticles (Se-NPs) were effectively established for Pseudomonas aeruginosa and Staphylococcus aureus biofilms. The possible impact of myco-synthesized novel cellulose-based selenium nanoparticles tertiary composite on the biofilm formation of P. aeruginosa , S. aureus , and Candida albicans was evaluated in this study. TC exhibited constant biofilm inhibition against P. aeruginosa , S. aureus , and C. albicans , while the results obtained from cytotoxicity of Se-NPs and TC showed that, alteration occurred in the normal cell line of lung fibroblast cells (Wi-38) was shown as loss of their typical cell shape, granulation, loss of monolayer, shrinking or rounding of Wi-38 cell with an IC 50 value of where 461 and 550 ppm respectively. • Novel tertial composite based on TEMPO cellulose, chitosan, starch and biosynthesized selenium nanoparticles was synthesized. • This composite was fully characterized using UV, FT-IR, XRD, SEM with EDX, particle distribution and mapping. • This promising composite exhibited potential anti-biofilm activity which produced by microbes. [ABSTRACT FROM AUTHOR]

• Extracts of different parts of Gomphrena celosioides showed promising antibacterial activity against selected β-lactamase producing uropathogens. • Extracts from Gomphrena celosioides exhibited concentration and time-dependent patterns of antibacterial activity. • Hot water extracts from Gomphrena celosioides exhibited potent anti-biofilm activity. • All extracts tested showed a relatively safe margin in the cytotoxicity assay, indicating that pharmacological activity displayed was not as a result of toxicity. Gomphrena celosioides Mart is used traditionally for the treatment of urinary tract infections (UTIs) and related diseases in Asia and Africa. The study evaluated the antibacterial and anti-biofilm potentials of G. celosioides against β-lactamase producing Escherichia coli, Klebsiella pneumoniae , and Staphylococcus aureus. The leaves, twigs, flowers and a combination of all plant parts of G. celosioides were extracted with hot water and acetone. Antibacterial activity was investigated through spectrophotometric and p -iodonitrotetrazolium chloride colorimetric methods. The crystal violet staining method was employed to determine the biofilm inhibition ability of the extracts. Safety levels of the extracts was evaluated against Vero monkey kidney cells through the MTT colorimetric assay. No antibacterial activity was displayed by any of the water extracts against tested organisms. However, all acetone extracts showed good antibacterial activity with minimum inhibitory concentrations (MICs) from 0.04 to 0.31 mg/mL. This corresponded to minimum percentage bacteriostatic activity ranging from 50.5 to 90%, showing a dose dependent pattern. All extracts including the water extracts, which did not show any sign of antibacterial activity at the highest concentration tested, showed promising anti-biofilm activity above 50% against all strains at the planktonic and biofilm formation stages. However, activity exhibited by the acetone extracts against E. coli at 0 and 24 h was weak. The tested MICs of acetone extracts including ciprofloxacin in the proliferation assay were more active against the organisms at 24 h except for S. aureus where all samples were more active at 18 h. A selectivity index between 0.61 and 4.75 showed that the extracts are relatively safe. Following the promising biological activity observed in this study, future studies such as identification of active constituents, mechanisms of action and in vivo evaluations are required. [ABSTRACT FROM AUTHOR]

Vibrio parahaemolyticus is a major seafood-borne pathogen causing significant economic losses in aquaculture systems. Therefore, application of phage encoded enzymes, particularly endolysin, as a new strategy for effective biocontrol and therapeutic agent against bacterial diseases. In the present study, we synthesized endolysin gene (Vplys60) of bacteriophage qdv001 and biochemically characterized by expressing in Pichia pastoris X-33. In addition to, we also investigated the anti-biofilm and anti-vibriosis activity of Pichia -expressing Vplys60 against vibrio challenged in vivo aquaculture model, Artemia franciscana. The result indicated that the predicted molecular size of Pichia expressed Vplys60 was approximately 28 kDa as verified by SDS-PAGE and zymogram. Vplys60 manifested stable activity over broad range of pH (6–10), temperatures (37–75 °C) and salinity (100–600 mM NaCl). Biochemical and in silico analysis revealed that addition of calcium ion (Ca2+) enhanced the lytic activity of Vplys60 whereas other metal ions inhibited the activity. Additionally, calcium-dependent Vplys60 has showed a strong amidase activity by cleaving the peptidoglycan of V. parahaemolyticus. Our data also showed that Vplys60 (75 μg/ml) significantly inhibits biofilm formation (91.6%) and significantly reduced the bacterial population. The in vivo challenge study showed enhanced survival rate in combination with reduced vibrio load in Artemia after administration of Pichia -expressing Vplys60. • Phage-derived enzybiotic (Vplys60) was successfully expressed in methylotrophic yeast, Pichia pastoris X-33. • In silico and biochemical characterization of Vplys60 revealed Ca2+ is an essential metal ion for its lytic activity. • Functional analysis of purified Vplys60 exhibited amidase activity. • Vplys60 (75 μg/ml) efficiently disrupted biofilm formation by Vibrio parahaemolyticus MTCC-451. • Pichia-expressing Vplys60 was enhanced survival rate and reduced Vibrio load in Artemia franciscana. [ABSTRACT FROM AUTHOR]

Outbreaks of multidrug-resistant bacteria are increasingly reported at the clinical setting. The antimicrobial, anti-biofilm, anti-quorum sensing, and anti-oxidant activities of four essential oils extracted from Cinnamomum verum , Origanum majorana, Thymus vulgaris, and Eugenia caryophyllata against Gram-positive and Gram-negative multidrug-resistant bacteria were evaluated in vitro. This study was conducted on 105 multidrug resistant clinical strains. Inhibition diameter zone, minimum inhibitory concentration, and minimum bactericide concentration of the oils were determined using agar disc diffusion method and microdilution. The ability of the 4 essential oils to inhibit the production of bacterial biofilms was tested on polystyrene plates, as well as their inhibitory effect on the production of violacein by Chromobacterium violaceum CV026. The anti-oxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl scavenging method. Essential oils of Cinnamomum verum , Thymus vulgaris and Eugenia caryophyllata showed an important antibacterial activity. The inhibition diameter zone was higher than 20 mm for 90.24 %, 85.71 % and 60.95 % of strains respectively. These essential oils have a remarkable anti-biofilm and anti-quorum sensing activities against almost all the species studied. Clove extract revealed the highest anti-oxidant activity (Pourcentage of inhibtion of DPPH = 90.3 %). These results supported the use of the 4 essential oils as alternative or complementary agents to treat infections caused by multidrug-resistant bacteria, and to prevent biofilm formation and quorum sensing signaling. They might be used as a safe anti-oxidants instead of harmful artificial ones. [ABSTRACT FROM AUTHOR]

Hereunder, we pioneered the synthesis of Copper Oxide nanoparticles (CuO NPs) utilizing Tragacanth gum (TG). The NPs were characterized using advanced techniques and assessed for different pharmaceutical and environmental perspectives. The successful formation of a colloidal NPs solution was confirmed by the appearance of a distinct black color and a distinct peak at 260 nm in UV–Visible spectrophotometry. The FTIR analysis unveiled a spectrum of functional groups responsible for the reduction and stabilization of CuO NPs. Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) revealed size of NPs as 36.24 nm and 28 ± 04 nm respectively. Energy Dispersive X-ray (EDX) Analysis indicated weight percentages of 70.38 % for Cu and 18.88 % for O, with corresponding atomic percentages. The X-ray Diffraction (XRD) analysis revealed the orthorhombic crystal structure of the prepared CuO NPs. Antimicrobial assessments through disc-diffusion assays demonstrated significant zones of inhibition (ZOI) against gram-positive bacterial strains (Bacillus Halodurans and Micrococcus leutus) and a gram-negative bacterial strain (E. coli). Against the fungal strain Aspergillus niger , a ZOI of 18.5 ± 0.31 mm was observed. The NPs exhibited remarkable antioxidant potential determined through 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and H 2 O 2 scavenging assays. At a concentration of 3 mg/mL, the NPs demonstrated biofilm inhibition rates of 96 %, 90 %, 89.60 %, and 72.10 % against Micrococcus luteus , Bacillus halodurans , MRSA and E.coli respectively. Furthermore, the CuO NPs showed a high photocatalytic potential towards the degradation of safranin dye under sunlight irradiation. In conclusion, the findings underline the promising multifunctional properties of TG-based CuO NPs for different practical applications. [ABSTRACT FROM AUTHOR]

• PEG/Cu-COF showed self-cascade reaction capable of depleting GSH and generating H 2 O 2. • PEG/Cu-COF were designed to responsive for exogenous and endogenous stimuli. • PEG/Cu-COF release Cu2+ and promote angiogenesis. • The approach enable the modality cotherapy through the "one-size-fits-all" strategy. Skin wound healing, particularly diabetic wound healing, is a common clinical challenge. Reducing bacterial infection and promoting angiogenesis are key strategies for diabetic wound healing. In this study, we construct the porphyrin-based Cu-covalent organic frameworks (Cu-COF) through a Schiff base condensation reaction, and then functionalize Cu-COF with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE), denoted as PEG/Cu-COF, for enhancing diabetic wound healing. PEG/Cu-COF exhibits dual enzymatic properties (glutathione (GSH) oxidase-like and peroxidase (POD)-like nanozymes), facilitating the depletion of GSH and the generation of reactive oxygen species (ROS) through a self-cascading enzymatic reaction, thereby leading to chemodynamic therapy (CDT). Density functional theory (DFT) calculations are employed to investigate the catalytic mechanism and the results reveal that Cu-COF exhibits higher catalytic activity for POD. Moreover, porphyrin-based COF generates singlet oxygen and localize heating under white light and near-infrared irradiation, respectively. Both in vitro and in vivo experiments demonstrate that PEG/Cu-COF exhibits multimodal synergistic sterilization and promotes angiogenesis, collagen deposition, and re-epithelialization during diabetic wound healing. This work highlights the potential utilization of PEG/Cu-COF for self-supplying hydrogen peroxide (H 2 O 2) and amplifying self-cascade reactions to address the limitations of enzymatic treatment, while the synergistic effect of phototherapy improves sterilization and minimizes side effects in vivo. [ABSTRACT FROM AUTHOR]

Mono or dual chitosan oligosaccharide lactate (COL)-conjugated pluronic F127 polymers, FCOL1 and FCOL2 were prepared, self-assembled to form micelles, and loaded with gatifloxacin. The Gati@FCOL1/Gati@FCOL2 micelles preparation process was optimized by QbD analysis. Micelles were characterized thoroughly for size, CMC, drug compatibility, and viscosity by GPC, DLS, SEM, IR, DSC, and XRD. The micelles exhibited good cellular uptake in both monolayers and spheroids of HCEC. The antibacterial and anti-biofilm activities of the micelles were evaluated on P. aeruginosa and S. aureus. The anti-quorum sensing activity was explored in P. aeruginosa by analyzing micelles' ability to produce virulence factors, including AHLs, pyocyanin, and the motility behavior of the organism. Gati@FCOL2 Ms was mucoadhesive, cornea-penetrant, antibacterial, and inhibited the biofilm formation by P. aeruginosa and S. aureus significantly more than Gati@FCOL1. A significant reduction in bacterial load in mice cornea was observed after Gati@FCOL2 Ms-treatment to the P. aeruginosa -induced bacterial keratitis-infected mice. [Display omitted] [ABSTRACT FROM AUTHOR]

The formation of biofilm is one of the important factors for bacteria to develop drug-resistant. A series of halogenated-pyrroles or pyrazoles containing thiazole groups as antibacterial agents were designed and synthesized to target biofilms. Among them, compound 8c showed antibacterial activity against various Gram-positive bacteria, particularly against vancomycin-resistant Enterococcus faecalis (MIC ≤0.125 μg/mL). Additionally, this compound significantly inhibited biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa at sub-MIC doses. Furthermore, compound 8c exhibited significantly lower mammalian cell toxicity compared to pyrrolomycin C and its hepatic microsomal metabolic stability in various species was also evaluated. Further experiment on the infection model of Galleria mellonella proved that the compound was effective in vivo. [Display omitted] • Thiazolyl-halogenated pyrroles or pyrazoles were synthesized for the first time and displayed good antibacterial activity. • Compound 8c , 9b , 10a and 10b effectively inhibited staphylococcal and Pseudomonas aeruginosa biofilm formation at sub-MICs. • Compound 8c showed acceptable PK property, reduced toxicity and effective in vivo activity on Galleria mellonella model. [ABSTRACT FROM AUTHOR]

Proteus mirabilis is known to cause Catheter-associated urinary tract infections (CAUTIs), which exhibit virulence factors linked to forming biofilms. Aptamers have recently been explored as potential anti-biofilm agents. This study demonstrates the anti-biofilm activity of aptamer (PmA2G02) targeting P. mirabilis 1429T, a pathogenic bacteria known to cause Catheter-associated urinary tract infections (CAUTIs). The studied aptamer inhibited biofilm formation, swarming motility, and cell viability at a concentration of 3 μM. The study also showed that the PmA2G02 had a binding affinity towards fimbrial outer membrane usher protein (PMI1466), flagellin protein (PMI1619), and regulator of swarming behavior (rsbA), which are responsible for adhesion, motility, and quorum sensing, respectively. Crystal violet assay, SEM, and confocal imaging confirmed the effectiveness of the PmA2G02 as an anti-biofilm agent. Moreover, as verified by qPCR, the expression levels of fimD , fliC2 , and rsbA were significantly reduced compared to the untreated group. This study suggests that aptamer may be a potential alternative to traditional antibiotics for the treatment of CAUTIs caused by P. mirabilis. These findings shed light on the mechanisms by which the aptamer inhibits biofilm formation. [ABSTRACT FROM AUTHOR]

Hydrogels prepared with natural and synthetic polymers were found to be applicable for the development of resistance against some Gram positive and negative bacterial species. Numerous studies have shown that chitosan polymers can be advantageous to be used in medicine due to their high antibacterial activity. In this study, biocompatible yellow cantorone oil doped hydrogels (chitosan/poly(vinyl alcohol) based) with antimicrobial properties were synthesized. The structural, morphological, swelling and mechanical properties of these biocompatible hydrogels prepared by double crosslinking were investigated and characterized. FTIR spectroscopy showed the appearance of new imine and acetal bonds due to both covalent cross-linking. In vitro cytotoxicity evaluation revealed that hydrogels showed weak cytotoxic effect. In the antimicrobial evaluation, it was determined that the hydrogel containing only chitosan showed better antimicrobial effect against Escherichia coli , Pseudomonas auriginosa , Staphylococcus aureus and Enterococcus faecalis bacteria than the one containing St. John's Wort oil. The antibacterial effect of polyvinyl alcohol/chitosan hydrogel was low. In our wound healing study, chitosan hydrogel loaded with yellow St. John's Wort oil was more effective in reducing wound size. [ABSTRACT FROM AUTHOR]

A high slime-producing Lactobacillus fermentum strain (named as L. fermentum S1) was isolated from traditional fermented Fuyuan pickle, which was made of white turnip and collected from Fuyuan county, Yunnan province, China. We extracted and purified the exopolysaccharides from L. fermentum S1, and investigated their preliminary structure characteristics and biological activities. Three purified exopolysaccharide fractions, designated as EPS1, EPS2 and EPS3, were obtained from the culture supernatant of L. fermentum S1 by ethanol precipitation, anion exchange and gel filtration chromatography. The EPS2 and EPS3 were homogeneous with molecular weights of 4.45 × 106 and 2.82 × 106 Da, respectively. All the purified EPS fractions were composed of glucose, galactose, mannose and arabinose, but with different molar ratios. EPS1, EPS2 and EPS3 presented different surface morphologies and their degradation temperatures were 302.7°C, 316.3°C and 316.9°C, respectively. Bioactivity research showed that L. fermentum S1 EPS elicited free radical scavenging capacity and ferric reducing antioxidant power, and 1 mg/mL of EPS significantly improved the gastrointestinal transit tolerance of non EPS-producing strain L. fermentum LG1. Moreover, S1 EPS had a favorable anti-biofilm activity against Escherichia coli and Staphylococcus aureus. These results indicated that S1 EPS could be explored as a promising functional adjunct for application in foods. • Three purified EPS fractions were obtained from Lactobacillus fermentum S1. • EPS fractions presented different surface morphologies and thermal properties. • EPS exhibited potent antioxidant properties in vitro. • EPS significantly improved gastrointestinal transit tolerance of L. fermentum LG1. • EPS had a favorable anti-biofilm activity against Escherichia coli and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

• Mono-rhamnolipids (mono-RLs) biosurfactant are commercially important. • P. aeruginosa strain CR1 exclusively produced considerable amount of mono-RLs. • Pyocyanin (PYO) produced by strain CR1 inhibited biofilm formation. • Strain CR1 is prime bioresource for industrial production of mono-RLs and PYO. Biosurfactant - Rhamnolipids (RLs) and antibacterial toxin - pyocyanin (PYO) produced by Pseudomonas aeruginosa strains have great potential for biotechnological applications. Generally, RLs are produced as a mixture of di-rhamnolipids (di-RLs) and mono-rhamnolipids (mono-RLs). Mono-RLs possess superior emulsification and antimicrobial properties and are costlier than di-RLs. In this study, a taxonomic outlier P. aeruginosa strain CR1 isolated from rhizosphere soil was explored for mono-RLs and PYO production. Phylogenetically strain CR1 resembles avirulent outlier P. aeruginosa strain ATCC9027, lacks archetypical virulence genes and harbors unique pathways for the synthesis of solely mono-RLs and PYO. Strain CR1 produced RL biosurfactant which efficiently emulsified hydrocarbons, showed hemolysis and inhibited Bacillus subtilis. At 37 °C, strain CR1 exclusively produced 21.77 g L−1 and 19.22 g L−1 rhamnolipid in glycerol amended Luria Bertani (LB) medium and basal medium amended with rice bran oil, respectively after 54 h growth. Besides RL production was unaffected under varying nitrogen sources. Structural characterization using FTIR, TLC, and LC–MS confirmed that strain CR1 exclusively produced mono-RLs, majorly dominated by Rha-C 10 -C 10 , Rha-C 10 -C 8 , and CH 3 -Rha-C 12:2 -C 10:1. The compound was stable over a wide pH range (4–12), salinity (25%) and 100 °C indicating its applicability under harsh environmental conditions. In addition, strain CR1 produced 4.5 μg mL−1 PYO, which could efficiently inhibit biofilm formation by Bacillus species. The environmental outlier strain CR1 can be used for the industrial production of biotechnologically important mono-RLs and PYO. [ABSTRACT FROM AUTHOR]

A simple, efficient and eco-friendly method for the synthesis of 1,2-dihydroquinazolines has been developed using three-component reaction of readily available aromatic aldehydes, 2-aminobenzophenones, ammonium acetate with sulfamic acid as a green and recyclable catalyst. The significant features of this method include short reaction time, operational simplicity, high yields and high selectivity. Interestingly, the catalyst can be recovered and reused for up to four cycles without any loss in catalytic activity. By employing this method, a series of 23 compounds was synthesized and tested for antimicrobial activity against both Gram-positive and Gram-negative bacterial strains as well as a fungal strain. Among these, compounds 4l , 4v and 4w showed appreciable antibacterial activity selectively against Gram-positive bacteria, wherein compound 4w exhibited promising antibacterial activity with MIC value of 0.010 μMol L−1 against Staphylococcus aureus MTCC 96 and Micrococcus luteus MTCC 2470. In addition, 4w also showed promising bactericidal and biofilm formation inhibitory effects. [ABSTRACT FROM AUTHOR]

Root canal re-infection and weakening of roots are two main challenges in endodontics. The objectives of the study were: (1) to develop a novel root canal sealer containing dimethylaminohexadecyl methacrylate (DMAHDM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP), and (2) to investigate the effects on the physical, anti-biofilm, remineralizing ions, and hardness of human dentin for the first time. Methacrylate-resin dual-cured root canal sealer contained 5% DMAHDM, 0.15% NAg, and NACP at 10%, 20% and 30% mass fractions. The flow, film thickness, and Ca and P ions release were investigated. The effects of NACP on radicular dentin hardness after treatment with sodium hypochlorite (NaOCL) and ethylenediaminetetraacetic acid (EDTA) were assessed. Antibacterial properties were measured against Enterococcus faecalis (E. faecalis) -impregnated dentin blocks; colony-forming units (CFU) and live/dead assays were measured. Incorporating DMAHDM, NAg and NACP did not adversely influence the flow and film thickness properties. Sealer with 30% NACP neutralized the acid and increased the solution pH (p < 0.05). Sealer containing 30% NACP regenerated dentin minerals lost due to NaOCL and EDTA treatment, and increased the dentin hardness to match that of sound dentin (p > 0.1). Incorporating 5% DMAHDM and 0.15% NAg reduced biofilm CFU of E. faecalis -impregnated dentin blocks by nearly 3 logs when compared control group (p < 0.05). The novel therapeutic root canal sealer with triple bioactive agents of DMAHDM, NAg and NACP neutralized acid, raised the pH, regenerated dentin minerals, increased root dentin hardness, and reduced dentin-block-impregnated biofilm CFU by 3 logs. This new sealer with highly desirable antibacterial and remineralization properties are promising to increase the success rate of endodontic therapy and strengthen the tooth root structures. [ABSTRACT FROM AUTHOR]

The study sought to purify and characterize a novel bacteriocin from oral L. salivarius and studying the effect of L. salivarius and its bacteriocin against multidrug-resistant (MDR) P. aeruginosa in vivo and in vitro. Saliva Lactobacillus salivarius bacteriocin was prepared and purified. The molecular weight of purified L. salivarius bacteriocin was 13,500 Da protein. The antibacterial activity of purified salivaricin LHM was higher than crude (P < 0.05) and was active at a wide range of pH values, thermostable and has no lipid or carbohydrate moiety. The antibiofilm activity of salivaricin LHM was observed. In vivo , Lactobacillus salivarius and salivaricin LHM significantly decrease the effect of bacteria in the kidney and bladder, while there is an improvement of P. aeruginosa infection in ureter salivaricin LHM-treated groups (P < 0.05). Analysis of serum IL-10 and IL-4 levels revealed salivaricin LHM has prophylaxis effect. In conclusion, salivaricin LHM is protein in nature, without lipid or carbohydrate moieties, heat-stable and active at a wide range of pH values and can be classified as type II bacteriocin. Lactobacillus salivarius and salivaricin LHM has anti-pseudomonas activity, immunomodulatory by increasing pro-inflammatory cytokines and antibiofilm against P. aeruginosa urinary tract infection model in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Loureirin A is a major active component of Draconis sanguis , a traditional Chinese medicine. This work aimed to investigate the activity of loureirin A against Candida albicans biofilms. 2, 3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)reduction assay and scanning electron microscopy were used to investigate the anti-biofilm effect. Minimal inhibitory concentration testing and time-kill curve assay were used to evaluate fungicidal activity. Cell surface hydrophobicity (CSH) assay and hyphal formation experiment were respectively carried out to investigate adhesion and morphological transition, two virulence traits of C. albicans. Real-time RT-PCR was used to investigate gene expression. Galleria mellonella − C. albicans and Caenorhabditis elegans-C. albicans infection models were used to evaluate the in-vivo antifungal effect. Human umbilical vein endothelial cells and C. elegans nematodes were used to evaluate the toxicity ofloureirin A. Our data indicated that loureirin A had a significant effect on inhibiting C. albicans biofilms, decreasing CSH, and suppressing hyphal formation. Consistently, loureirin A down-regulated the expression of some adhesion-related genes and hypha/biofilm-related genes. Moreover, loureirin A prolonged the survival of Galleria mellonella and Caenorhabditis elegans in C. albicans infection models and exhibited low toxicity. Collectively, loureirin A inhibits fungal biofilms, and this effect may be associated with the suppression of pathogenic traits, adhesion and hyphal formation. [ABSTRACT FROM AUTHOR]

Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure–activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms. [ABSTRACT FROM AUTHOR]

Abstract The multifunctional biological active material design for bone tissue engineering is essential to induce osteoblast cell proliferation and attachment. Adhesion of bacteria on biomaterials to produce biofilms can be major contributors to the pathogenesis of implant material associated infections. This research work focuses on NPF& NBF elemental doping and functionalization of reduced graphene oxide using an imidazolium-based ionic liquid such as BMIM PF 6 and BMIM BF 4 by hydrothermal method. The resulting tri doped reduced graphene oxide (NPF-rGO and NBF-rGO) composite was further used as a scaffold for bone tissue engineering and anti-biofilm activities. The observation of the effect of NPF-rGO and NBF-rGO on the morphology, adhesion and cell proliferation of HOS cell was investigated. Moreover, the tri doped composite tested its antibiofilm properties against B. subtilis , E. coli , K. pneumoniae , and P. aeruginosa pathogenic bacteria. In-vitro studies clearly show the effectiveness of N, P, B, and F doping promoting the rGO mineralization, biocompatibility, and destruction of bacterial biofilm formation. The result of this study suggests that NPF-rGO and NBF-rGO hybrid material will be a promising scaffold for bone reaeration and implantation with a minimal bacterial infection. Graphical abstract Unlabelled Image Highlights • Nano-sphere and cube shaped NPF & NBF tri doped rGO was prepared by the assistance of BMIM PF6 and BMIM BF4 ionic liquid. • Ionic liquid has been acted as a functionalizing as well as templating agent with hetero atoms (N, P, B. F) source. • The structural and morphological modification of rGO with respect to ILs has been systematically investigated. • The cell viability and Morphological studies designated a significant proliferation of HOS during the culture time. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We have demonstrated the conjugation of WS 2 QD to the de novo designed AMPs. • The conjugated peptide is two times more potent than its free counterpart. • We have determined the three-dimensional solution structure of WS 2 conjugated AMPs. • Interplay between peptide and QD is translated to functional performances of AMPs. Abstract Two-dimensional (2D) tungsten disulfide (WS 2) quantum dots offer numerous promising applications in materials and optoelectronic sciences. Additionally, the catalytic and photoluminescence properties of ultra-small WS 2 nanoparticles are of potential interest in biomedical sciences. Addressing the use of WS 2 in the context of infection, the present study describes the conjugation of two potent antimicrobial peptides with WS 2 quantum dots, as well as the application of the resulting conjugates in antimicrobial therapy and bioimaging. In doing so, we determined the three-dimensional solution structure of the quantum dot-conjugated antimicrobial peptide by a series of high-resolution nuclear magnetic resonance (NMR) techniques, correlating this to the disruption of both model lipid and bacterial membranes, and to several key biological performances, including antimicrobial and anti-biofilm effects, as well as cell toxicity. The results demonstrate that particle conjugation enhances the antimicrobial and anti-biofilm potency of these peptides, effects inferred to be due to multi-dendate interactions for the conjugated peptides. As such, our study provides information on the mode-of-action of such conjugates, laying the foundation for their potential use in treatment and monitoring of infections. [ABSTRACT FROM AUTHOR]