The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides.

Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens in vitro and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of Staphylococcus aureus. Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of S. aureus within minutes due to protonophore activity. Varying the salt species and concentrations in buffers revealed that not only protons are transported, and we demonstrate the binding of the monovalent cations K+, Na+, and Li+ to lugdunin. By comparing known ionophores with various ion transport mechanisms, we conclude that the ion selectivity of lugdunin largely resembles that of 15-mer linear peptide gramicidin A. Direct interference with the main bacterial metabolic pathways including DNA, RNA, protein, and cell wall biosyntheses can be excluded. The previously observed synergism of lugdunin with dermcidin-derived peptides such as DCD-1 in killing S. aureus is mechanistically based on potentiated membrane depolarization. We also found that lugdunin was active against certain eukaryotic cells, however strongly depending on the cell line and growth conditions. While adherent lung epithelial cell lines were almost unaffected, more sensitive cells showed dissipation of the mitochondrial membrane potential. Lugdunin seems specifically adapted to its natural environment in the respiratory tract. The ionophore mechanism is refractory to resistance development and benefits from synergy with host-derived antimicrobial peptides. IMPORTANCE: The vast majority of antimicrobial peptides produced by members of the microbiome target the bacterial cell envelope by many different mechanisms. These compounds and their producers have evolved side-by-side with their host and were constantly challenged by the host's immune system. These molecules are optimized to be well tolerated at their physiological site of production, and their modes of action have proven efficient in vivo. Imbalancing the cellular ion homeostasis is a prominent mechanism among antibacterial natural products. For instance, over 120 naturally occurring polyether ionophores are known to date, and antimicrobial peptides with ionophore activity have also been detected in microbiomes. In this study, we elucidated the mechanism underlying the membrane potential-dissipating activity of the thiazolidine-containing cycloheptapeptide lugdunin, the first member of the fibupeptides discovered in a commensal bacterium from the human nose, which is a promising future probiotic candidate that is not prone to resistance development.

Iron Oxide Nanoparticles as Promising Antibacterial Agents of New Generation.

Antimicrobial resistance (AMR) is growing into a major public health crisis worldwide. The reducing alternatives to conventional agents starve for novel antimicrobial agents. Due to their unique magnetic properties and excellent biocompatibility, iron oxide nanoparticles (IONPs) are the most preferable nanomaterials in biomedicine, including antibacterial therapy, primarily through reactive oxygen species (ROS) production. IONP characteristics, including their size, shape, surface charge, and superparamagnetism, influence their biodistribution and antibacterial activity. External magnetic fields, foreign metal doping, and surface, size, and shape modification improve the antibacterial effect of IONPs. Despite a few disadvantages, IONPs are expected to be promising antibacterial agents of a new generation.

Studying the Effect of Magnetron Copper Deposition on the Surface Topography of Biodegradable Antibacterial Coating.

Background: The surface properties of the materials used significantly influence the success and longevity of medical implants. Increasing surface roughness promotes osteoblast activity and osseointegration, while biodegradable materials such as copper have shown potential for antimicrobial applications. However, the effect of coating parameters on surface topography is not well investigated. Methods: Sputtering of copper was performed using EPOS-PVD-440 system (Zeleno-grad, Russia). The samples were examined by Scanning Electron Microscopy (SEM) with subsequent image processing in Mountains software (Digital Surf). Antibacterial efficacy was evaluated against Staphylococcus aureus by measuring the zone of inhibition. Additionally, copper ion release was monitored over time to assess its correlation with changes in surface topography. Results: Higher sputtering currents increased surface roughness and particle size, with a significant release of copper ions within the first 24 hr of immersion. Samples sputtered at higher currents exhibited coarser grain structures. The release of copper ions in the simulated biological environment led to further changes in surface topography, highlighting the critical influence of sputtering parameters on coating properties. Conclusion: Optimizing magnetron copper deposition parameters enhances the surface topography and antibacterial effectiveness of biodegradable coatings on implants.

Photocatalytic Generation of Singlet Oxygen by Graphitic Carbon Nitride for Antibacterial Applications.

Carbon-based functional nanocomposites have emerged as potent antimicrobial agents and can be exploited as a viable option to overcome antibiotic resistance of bacterial strains. In the present study, graphitic carbon nitride nanosheets are prepared by controlled calcination of urea. Spectroscopic measurements show that the nanosheets consist of abundant carbonyl groups and exhibit apparent photocatalytic activity under UV photoirradiation towards the selective production of singlet oxygen. Therefore, the nanosheets can effectively damage the bacterial cell membranes and inhibit the growth of bacterial cells, such as Gram-negative Escherichia coli, as confirmed in photodynamic, fluorescence microscopy, and scanning electron microscopy measurements. The results from this research highlight the unique potential of carbon nitride derivatives as potent antimicrobial agents.

Biosynthesis of iron oxide nanoparticles using plant extracts and evaluation of their antibacterial activity.

The biosynthesis of iron oxide nanoparticles has received increasing attention in the field of food nanotechnology because of their non-toxicity, high efficiency, high antibacterial power, and decontamination features. Therefore, biosynthesis of iron oxide nanoparticles (nFe) was prepared from the leaves of some vegetables, such as cabbage (C) and turnips (T), as well as moringa leaves (M). Alcoholic extracts of these nanoparticles were also tested on Staphylococcus aureus and Escherichia coli to evaluate their antibacterial activity. The results revealed that the particle sizes of the biosynthesis nanomaterials studied ranged from 12.99 to 22.72 nm, and the particles were spherical, irregular, and surrounded by black color. It also contains many functional groups and minerals. Iron nanoparticles modified with Moringa oleifera extract at a concentration of 200 ppm had the highest phenol content compared to other biosynthesis nanoparticles studied. TnFe and MnFe at 200 ppm had a maximum zone of inhibition of 25 mm and 24 mm against Staphylococcus aureus and Escherichia coli, respectively. While the minimum inhibition zone of 8.0 mm was observed at 25 ppm for nFe against Escherichia coli. Therefore, it is recommended to use these extracts of biosynthesis iron oxide nanoparticles as antibacterial agents for stored foods.

Surface treatment of artificial implants with hybrid nanolayers: results of antibacterial tests, leachates and scanning electron microscope analysis.

Purpose: The aim of this study was to evaluate the antibacterial efficacy of surface-treated hernia implants modified by a hybrid nanolayer with incorporated Ag, Cu, and Zn cations using the sol-gel method. Methods: The materials (polypropylene, polyester, and polyvinylidene difluoride) were activated by vacuum plasma treatment or UV C radiation, then modified and tested for bacterial strains of Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). The AATCC 100 (2019) method for quantitative and the ISO 20645 agar plate propagation method for qualitative evaluation of microbiological efficacy were used. The gradual release of incorporated ions was monitored over time in simulated body fluids (blood plasma, peritoneal fluid) and physiological saline using an inductively coupled plasma mass spectrometer. The thickness and the homogeneity of the layers were measured for individual random samples with scanning electron microscope analysis (SEMA) and evaluated with an elemental analysis. Results: Qualitative and quantitative microbiological tests clearly show the great suitability of vacuum plasma and UV C with sol AD30 (dilution 1:1) surface treatment of the implants. The absolute concentration of Ag, Cu, and Zn cations in leachates was very low. SEMA showed a high degree of homogeneity of the layer and only very rare nanocracks by all tested materials appear after mechanical stress. Conclusion: This study confirms that surface treatment of meshes using the sol-gel method significantly increases the antibacterial properties. The nanolayers are sufficiently mechanically resistant and stable and pose no threat to health.

Autologous serum protein stabilized silver quantum clusters as host-specific antibacterial agents.

Aim: To synthesize host-specific serum protein stabilized silver quantum clusters and assess their preclinical safety as potential antibacterial agents. Materials & methods: Ag-QC-NanoSera (Ag-QCNS) were synthesized using bovine, human and murine sera. Antibacterial efficacy was evaluated against E. coli (including antibiotic-resistant strain), S. aureus and P. aeruginosa. Biocompatibility, hemocompatibility and antibacterial mechanism were also investigated. Preclinical safety and biodistribution of autologous Ag-QCNS were assessed in BALB/c mice over 28 days. Results: Ag-QCNS showed high biocompatibility, hemocompatibility and high antibacterial activity at ∼12.72 µg/ml Ag equivalent. Intracellular ROS and bacterial membrane damage were confirmed as antibacterial mechanism. Ag-QCNS were established as preclinically safe. Conclusion: Ag-QCNS demonstrate potential as next-generation host-specific nanotheranostic antibacterial agents, enhancing the safety and efficacy while combating antibiotic resistance.

[Box: see text].

Evaluation of the adherence to surgical antibiotic prophylaxis recommendations and associated factors in a University Hospital: A cross-sectional study.

BACKGROUND: Surgical antibiotic prophylaxis (SAP) is an important preventive measure, aiming to minimize surgical site infections. However, despite evidence-based guidelines, adherence to SAP protocols remains suboptimal in clinical practice. The aim of this study was to assess the adequacy of SAP in a high-complexity hospital and investigate associated factors. METHODS: A cross-sectional design was conducted, involving surgeries performed by expert teams in cardiology, urology, neurology, and gastrointestinal. SAP prescriptions were evaluated based on indication, antibiotic choice, dosage, and duration, according to the hospital protocol. Data analysis included descriptive statistics and association tests between protocol adherence and patient demographics, clinical variables, surgical teams, and types of surgeries. RESULTS: Out of 1,864 surgeries, only 20.7% adhered to SAP protocols. Lower adherence rates were observed for antibiotic choice and duration of prophylaxis. Neurological surgeries exhibited significantly lower adherence, particularly concerning antibiotic choice and duration. Factors associated with nonadherence included elevated preoperative blood glucose levels, prolonged hospitalization, and extended surgical duration. Logistic regression analysis identified surgical teams as significant factors influencing protocol adherence. CONCLUSIONS: Despite the relatively high adherence to antibiotic dosage, challenges persist in antibiotic choice and duration adjustment. Poor glycemic control, prolonged surgery, and surgical teams were variables associated with inappropriate practice.

Light-activated Nanocatalyst for Precise In-situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in-situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

Recent advances in the development of bacterial response regulators inhibitors as antibacterial and/or antibiotic adjuvant agent: A new approach to combat bacterial resistance.

The number of new antibacterial agents currently being discovered is insufficient to combat bacterial resistance. It is extremely challenging to find new antibiotics and to introduce them to the pharmaceutical market. Therefore, special attention must be given to find new strategies to combat bacterial resistance and prevent bacteria from developing resistance. Two-component system is a transduction system and the most prevalent mechanism employed by bacteria to respond to environmental changes. This signaling system consists of a membrane sensor histidine kinase that perceives environmental stimuli and a response regulator which acts as a transcription factor. The approach consisting of developing response regulators inhibitors with antibacterial activity or antibiotic adjuvant activity is a novel approach that has never been previously reviewed. In this review we report for the first time, the importance of targeting response regulators and summarizing all existing studies carried out from 2008 until now on response regulators inhibitors as antibacterial agents or / and antibiotic adjuvants. Moreover, we describe the antibacterial activity and/or antibiotic adjuvants activity against the studied bacterial strains and the mechanism of different response regulator inhibitors when it's possible.

Preparation of Andrographis Paniculata and Rosa Formulation and its Antibacterial Activity Against Urinary Tract Infection Causing Pathogens.

Andrographis Paniculata also known as the "King of Bitters" is a herbal medicine of the Acanthaceae family which is native to India and Sri Lanka. Andrographis Paniculata is a very useful medicinal plant as it has antioxidant, antidiabetic, antipyretic, anticancer properties. The main antibacterial activity of Andrographis Paniculata is due to the presence of andrographolide and arabinogalactan proteins. The medicinal properties of rose are mostly due to their abundance in phenolic compounds. They have many pharmacological properties like antibacterial, antioxidant, thrombolytic, and anticancer properties. The hips of the rose plant have Vitamin C in a concentration that is three times more than a citrus fruit that can be used in the treatment of a flu or a cold. Mueller-Hinton agar was utilized for this activity to determine the zone of inhibition. The plant extracts with different concentrations were loaded, and the plates were incubated for 24 hours at 37°C. After the incubation time, the zone of inhibition was measured. The results of this study are significant because they demonstrate the antibacterial activity of Andrographis Paniculata and Rosa against three bacterial pathogens. This suggests that the formulation of Andrographis Paniculata and Rosa has potential as a natural antibacterial agent. Further studies are needed to explore the mechanism of action and potential applications of this formulation. In conclusion, the study shows that the formulation of Andrographis Paniculata and Rosa has significant antibacterial activity against Klebsiella, Escherichia Coli, and Enterococcus Faecalis. This suggests that the formulation of Andrographis Paniculata and Rosa has potential as a natural antibacterial agent that could be further explored for its potential use in the treatment of bacterial infections.

Mechanisms of Triton X-100 reducing the Ag+-resistance of Enterococcus faecalis.

To investigate the mechanism of Triton X-100 (TX-100) reducing the Ag+-resistance of Enterococcus faecalis (E. faecalis), and evaluate the antibacterial effect of TX-100 + Ag+ against the induced Ag+-resistant E. faecalis (AREf). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of AgNO3 against E. faecalis with/without TX-100 were determined to verify the enhanced antibacterial activity. Transmission electron microscopy (TEM) was used to observe the morphological changes of E. faecalis after treatment. The intra- and extracellular concentration of Ag+ in treated E. faecalis was evaluated using inductively coupled plasma mass spectrometer (ICP-MS). The changes in cell membrane potential and integrity of treated E. faecalis were also observed using the flow cytometer. Moreover, AREf was induced through continuous exposure to sub-MIC of Ag+ and the antibacterial effect of TX-100 + Ag+ on AREf was further evaluated. The addition of 0.04% TX-100 showed maximal enhanced antibacterial effect of Ag+ against E. faecalis. The TEM and ICP-MS results demonstrated that TX-100 could facilitate Ag+ to enter E. faecalis through changing the membrane structure and integrity. Flow cytometry further showed the effect of TX-100 on membrane potential and permeability of E. faecalis. In addition, the enhanced antibacterial effect of TX-100 + Ag+ was also confirmed on induced AREf. TX-100 can facilitate Ag+ to enter E. faecalis through disrupting the membrane structure and changing the membrane potential and permeability, thus reducing the Ag+-resistance of E. faecalis and enhancing the antibacterial effect against either normal E. faecalis or induced AREf.

Exploring the interaction of N-(benzothiazol-2-yl)pyrrolamide DNA gyrase inhibitors with the GyrB ATP-binding site lipophilic floor: A medicinal chemistry and QTAIM study.

N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring or to the carboxamide nitrogen atom were prepared and studied for their inhibition of Escherichia coli DNA gyrase by supercoiling assay. Compared to inhibitors bearing the substituents at position 4 of the benzothiazole ring, the inhibition was attenuated by moving the substituent to position 3 and further to the carboxamide nitrogen atom. A co-crystal structure of (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex with E. coli GyrB24 (ATPase subdomain) was solved, revealing the binding mode of this type of inhibitor to the ATP-binding pocket of the E. coli GyrB subunit. The key binding interactions were identified and their contribution to binding was rationalised by quantum theory of atoms in molecules (QTAIM) analysis. Our study shows that the benzyl or phenethyl substituents bound to the benzothiazole core interact with the lipophilic floor of the active site, which consists mainly of residues Gly101, Gly102, Lys103 and Ser108. Compounds with substituents at position 3 of the benzothiazole core were up to two orders of magnitude more effective than compounds with substituents at the carboxamide nitrogen. In addition, the 6-oxalylamino compounds were more potent inhibitors of E. coli DNA gyrase than the corresponding 6-acetamido analogues.

Surface chemistry engineered selenium nanoparticles as bactericidal and immuno-modulating dual-functional agents for combating methicillin-resistant Staphylococcus aureus Infection.

Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, in vivo studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8+ and CD4+ T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.

Phytochemical investigation of the n-hexane-extracted oil from four umbelliferous vegetables using GC/MS analysis in the context of antibacterial activity.

Umbelliferous (Apiaceae) vegetables are widely consumed worldwide for their nutritive and health benefits. The main goal of the current study is to explore the compositional heterogeneity in four dried umbelliferous vegetables viz, celery, coriander, dill, and parsley targeting their volatile profile using gas chromatography-mass spectrometry (GC-MS). A total of 133 volatile metabolites were detected belonging to 12 classes. Aromatic hydrocarbons were detected as the major components of the analyzed vegetables accounting ca. 64.0, 62.4, 59.5, and 47.8% in parsley, dill, celery, and coriander, respectively. Aliphatic hydrocarbons were detected at ca. 6.39, 8.21, 6.16, and 6.79% in parsley, dill, celery, and coriander, respectively. Polyunsaturated fatty acids (PUFA) of various health benefits were detected in parsley and represented by roughanic acid and α-linolenic acid at 4.99 and 0.47%, respectively. Myristicin and frambinone were detected only in parsley at 0.45 and 0.56%. Investigation of antibacterial activity of umbelliferous vegetables n-hexane extract revealed a moderate antibacterial activity against Gram-positive and Gram-negative bacteria with higher activity for celery and dill against Staphylococcus aureus with inhibition zone 20.3 mm compared to 24.3 mm of the standard antibacterial drug.

Antibacterial Activity of Epigallocatechin-3-gallate (EGCG) Loaded Lipid-chitosan Hybrid Nanoparticle against Planktonic Microorganisms.

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from Green Tea, is one of the sources of natural bioactive compounds which are currently being developed as medicinal ingredients. Besides other biological activities, this natural compound exhibits anti-cariogenic effects. However, EGCG has low physical-chemical stability and poor bioavailability. Thus, the purpose of this study was to develop and characterize lipid-chitosan hybrid nanoparticle with EGCG and to evaluate its in vitro activity against cariogenic planktonic microorganisms. Lipid-chitosan hybrid nanoparticle (LCHNP-EGCG) were prepared by emulsion and sonication method in one step and characterized according to diameter, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), mucoadhesion capacity and morphology. Strains of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei were treated with LCHNP- EGCG, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. LCHNP-EGCG exhibited a size of 217.3 ± 5.1 nm with a low polydispersity index (0.17) and positive zeta potential indicating the presence of chitosan on the lipid nanoparticle surface (+33.7 mV). The LCHNP-EGCG showed a spherical morphology, high stability and a mucoadhesive property due to the presence of chitosan coating. In addition, the EGCG encapsulation efficiency was 96%. A reduction of almost 15-fold in the MIC and MBC against the strains was observed when EGCG was encapsulated in LCHNP, indicating the potential of EGCG encapsulation in lipid-polymer hybrid nanoparticles. Taking the results together, the LCHNP-EGCG could be an interesting system to use in dental care due to their nanometric size, mucoadhesive properties high antibacterial activity against relevant planktonic microorganisms.

Unearthing naturally-occurring cyclic antibacterial peptides and their structural optimization strategies.

Natural products with antibacterial activity are highly desired globally to combat against multidrug-resistant (MDR) bacteria. Antibacterial peptide (ABP), especially cyclic ABP (CABP), is one of the abundant classes. Most of them were isolated from microbes, demonstrating excellent bactericidal effects. With the improved proteolytic stability, CABPs are normally considered to have better druggability than linear peptides. However, most clinically-used CABP-based antibiotics, such as colistin, also face the challenges of drug resistance soon after they reached the market, urgently requiring the development of next-generation succedaneums. We present here a detail review on the novel naturally-occurring CABPs discovered in the past decade and some of them are under clinical trials, exhibiting anticipated application potential. According to their chemical structures, they were broadly classified into five groups, including (i) lactam/lactone-based CABPs, (ii) cyclic lipopeptides, (iii) glycopeptides, (iv) cyclic sulfur-rich peptides and (v) multiple-modified CABPs. Their chemical structures, antibacterial spectrums and proposed mechanisms are discussed. Moreover, engineered analogs of these novel CABPs are also summarized to preliminarily analyze their structure-activity relationship. This review aims to provide a global perspective on research and development of novel CABPs to highlight the effectiveness of derivatives design in identifying promising antibacterial agents. Further research efforts in this area are believed to play important roles in fighting against the multidrug-resistance crisis.

UiO-66/AgNPs Coating for Dental Implants in Preventing Bacterial Infections.

Titanium (Ti)-based biomaterials lack inherent antimicrobial activities, and the dental plaque formed on the implant surface is one of the main risk factors for implant infections. Construction of an antibacterial surface can effectively prevent implant infections and enhance implant success. Silver nanoparticles (AgNPs) exhibit broad antibacterial activity and a low tendency to induce drug resistance, but AgNPs easily self-aggregate in the aqueous environment, which significantly impairs their antibacterial activity. In this study, UiO-66/AgNP (U/A) nanocomposite was prepared, where zirconium metal-organic frameworks (UiO-66) were employed as the confinement matrix to control the particle size and prevent aggregation of AgNPs. The bactericidal activity of U/A against methicillin-resistant Staphylococcus aureus and Escherichia coli increased nearly 75.51 and 484.50 times compared with individually synthesized Ag. The antibacterial mechanism can be attributed to the enhanced membrane rupture caused by the ultrafine AgNPs on UiO-66, leading to protein leakage and generation of intracellular reactive oxygen species. Then, U/A was loaded onto Ti substrates (Ti-U/A) by using self-assembly deposition methods to construct an antibacterial surface coating. Ti-U/A exhibited excellent antibacterial activities and desired biocompatibility both in vitro and in vivo. The U/A nanocomposite coating technique is thus expected to be used as a promising surface modification strategy for Ti-based dental implants for preventing dental implant infections.

Antibacterial Agents for Composite Resin Restorative Materials: Current Knowledge and Future Prospects.

Resin composites became the material of choice for direct restorations in anterior and posterior teeth. Despite the revolutionary improvement in the material, restoration failure is still a major drawback due to the material's inherent negative properties, including a lack of antibacterial effects. Therefore, many attempts have been made to incorporate antibacterial agents into resin composite materials to improve their antimicrobial properties and prevent secondary caries formation. Multiple laboratory studies have been conducted using different antibacterial agents, such as quaternary ammonium compounds, methacryloyloxydodecylpyridinium bromide, magnesium oxide nanoparticles, chlorhexidine, and chitosan. This review provides a glance at the current status of these materials and the research directions needed in the future.

Bioisosteric replacement strategy leads to novel DNA gyrase B inhibitors with improved potencies and properties.

The identification of novel 4-hydroxy-2-quinolone-3-carboxamide antibacterials with improved properties is of great value for the control of antibiotic resistance. In this study, a series of N-heteroaryl-substituted 4-hydroxy-2-quinolone-3-carboxamides were developed using the bioisosteric replacement strategy. As a result of our research, we discovered the two most potent GyrB inhibitors (WBX7 and WBX18), with IC50 values of 0.816 µM and 0.137 µM, respectively. Additional antibacterial activity screening indicated that WBX18 possesses the best antibacterial activity against MRSA, VISA, and VRE strains, with MIC values rangingbetween0.5and 2 µg/mL, which was 2 to over 32 times more potent than that of vancomycin. In vitro safety and metabolic stability, as well as in vivo pharmacokinetics assessments revealed that WBX18 is non-toxic to HUVEC and HepG2, metabolically stable in plasma and liver microsomes (mouse), and displays favorable in vivo pharmacokinetic properties. Finally, docking studies combined with molecular dynamic simulation showed that WBX18 could stably fit in the active site cavity of GyrB.