Antibacterial Mechanism Research Articles

Effect of nanoemulsion loaded with macela (Achyrocline satureioides) on the ultrastructure of Staphylococcus aureus and the modulating activity of antibiotics

Nanoformulations with herbal actives for treating bovine mastitis present an alternative for controlling bacterial infections in the emerging scenario of antimicrobial resistance. In this study, we investigated macela (Achyrocline satureioides) nanoemulsion (NE-ML), a formulation developed for the treatment of bovine mastitis (registered under Brazilian patent application BR 10 2021 008630 0), in the context of its bactericidal mechanism(s) of action and potential synergism with commercial antimicrobials. The effect of NE-ML on the integrity and cell permeability of Staphylococcus aureus was evaluated by measuring the electrical conductivity of bacterial suspensions exposed to different concentrations of NE-ML and by assessing the release of cellular constituents. Damage to bacterial ultrastructures was analyzed by transmission electron micrographs. The synergism of NE-ML with beta-lactam antibiotics and aminoglycosides was evaluated by the checkerboard test method against S. aureus (n = 6). The relative electrical conductivity of the bacterial solution gradually increased over time, reaching high values after exposure to 1xMIC (52.3%) and 2xMIC (75.34%) of NE-ML. Total proteins were detected in the bacterial suspensions exposed to NE-ML, increasing in concentration over exposure time (p < 0.05). Through bacterial micrographs, we observed that exposure to NE-ML (1xMIC) affected the integrity of the plasma membrane with invaginations in the cytosolic region and alterations in the cell wall. The increase in NE-ML concentration resulted in greater damage to the ultrastructure of S. aureus with changes in bacterial cell division patterns. When NE-ML was combined with the beta-lactam antimicrobials, the interaction was indifferent, indicating no modulation of antimicrobial resistance. In contrast, when combined with the aminoglycoside, a synergistic interaction did occur. These general findings suggest that the bactericidal action of NE-ML begins in the plasma membrane, causing alterations in its permeability and integrity, and extends to the cell wall, cytoplasm, and cell division. Although synergy was restricted to the aminoglycoside by destabilizing the bacterial cell membrane, this suggests that NE-ML can induce the entry of other actives, potentially reducing their therapeutic doses. Understanding the mechanism of action of this new nanoformulation is certain to drive pharmacological advances, broaden the perspective of its in vivo use, and improve the treatment of bovine mastitis.

Silver Nanomaterials In Antimicrobial Applications

The article provides an overview of the different preparation methods, antimicrobial mechanisms and antimicrobial applications of silver nanomaterials. The synthesis methods of silver nanomaterials are mainly divided into physical synthesis, chemical synthesis and biosynthesis, among which biosynthesis is widely used due to its high purity and environmentally friendly products. The antibacterial mechanism of silver nanomaterials is relatively complex, which is the result of multiple ways such as disrupting the integrity of cell membranes, interfering with protein synthesis, affecting cell signaling and inhibiting DNA replication. The antibacterial performance, as the main property of silver nanomaterials, is widely used in fields such as biomedicine, antibacterial materials and wastewater treatment.

Synthesis of antibiofilm (1R,4S)-(-)-fenchone derivatives to control Pseudomonas syringae pv. tomato.

Biofilm plays a crucial role in Pseudomonas syringae pv. tomato (Pst) infection. We identified (1R,4S)-(-)-fenchone (FCH) as the most potent antibiofilm agent against Pst among 39 essential oil compounds. Subsequently, we synthesized a series of FCH oxime ester and acylhydrazine derivatives to explore more potent derivatives. II3 was screened out as the most potent derivative, exhibiting a minimal biofilm inhibitory concentration of 60 μg mL-1 and a lowest concentration with maximal biofilm inhibition (LCMBI) of 200 μg mL-1, lower than those of FCH (80 and 500 μg mL-1, respectively). II3 and FCH showed minimum inhibitory concentration values >1000 μg mL-1 and similar maximal biofilm inhibition extents of 48.7% and 49.5% at their respective LCMBIs, respectively. Meanwhile, neither of them influenced cell viability or the activity of metabolic enzymes at their respective LCMBIs. II3 at its LCMBI significantly reduced biofilm thickness, extracellular polysaccharide content, and pectinase and cellulase production indices. In vivo assay results indicated that II3 could preventatively reduce the bacterial contents in tomato leaves at its LCMBI, and when combined with kasugamycin (KSG) (10 μg mL-1), II3 achieved the same level of bacterial reduction as the sole application of KSG (70 μg mL-1), thereby reducing the required dosage of KSG. Mechanistic studies demonstrated that II3 can down-regulate biofilm-related genes and inhibit PsyR/PsyI quorum sensing system, which differs from the bactericidal mechanisms. These results underscore the potential of II3 as an antibiofilm agent for the control of Pst or FCH as a promising natural candidate for future in-depth optimization. © 2024 Society of Chemical Industry.

Synergistic antibacterial effect of 405 nm blue light-emitting diodes (LEDs) and gelatin film for inactivation of Escherichia coli O157:H7 and Salmonella typhimurium on stainless steel and fresh fruit peel

A combined antibacterial effect of 405 nm blue LEDs (BL) and gelatin film (G) was investigated on stainless steel (SUS) and fresh fruit peel for the inactivation of Escherichia coli O157:H7 and Salmonella Typhimurium. On the SUS, the sum of the individual treatments of G for 20 min and BL at 20 J/cm2 was <1 log reduction (log CFU/cm2). In comparison, combination treatment of G and BL (G + BL) at 20 J/cm2 exhibited 2.37 and 3.09 log reduction on E. coli O157:H7 and S. typhimurium. The G + BL treatment only increased a propidium iodide (PI) uptake, indicating that cell membrane damage occurred. In the G + BL treatment, reactive oxygen species (ROS) scavenging assay confirmed that ROS involved in the bactericidal mechanism. On orange peel, the G + BL treatment at 40 J/cm2 resulted in a 3.05 and 3.17 log reduction on E. coli O157:H7 and S. typhimurium. In contrast, the individual treatment of G for 40 min led to reductions of 0.63 log CFU/cm2 for E. coli O157:H7 and 0.50 log CFU/cm2 for S. typhimurium, while the BL treatment at 40 J/cm2 achieved reductions of 0.78 and 0.69 log CFU/cm2, respectively. A synergistic bactericidal effect was similarly observed in the combined treatment groups for both apple and grapefruit peels. In a color and texture analysis, G did not affect hardness, toughness, and visual color of fruit.

Evaluation of the bactericidal activity of plasma-activated NaCl solution (PAN) against foodborne pathogens: Inactivation mechanism and application to mackerel

The objective of this study was to assess the bactericidal effect of plasma-activated NaCl solution (PAN) against Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes and apply PAN as a brine salting solution for mackerel. To enhance the bactericidal effect of plasma-activated water (PAW), NaCl solutions (0, 3.5, 7, and 10 %) were treated with plasma for 20 and 40 min to generate PAN. Plasma-activated glycerol solution (PAG) was also included to evaluate the influence of water activity on plasma activation and its effect on microbial activity. Physicochemical analysis revealed that elevating the NaCl concentration of PAN led to a decrease in pH, an increase in oxidation–reduction potential, and higher levels of reactive species such as H2O2 and HOCl. PAN showed greater antibacterial activity compared to PAW and PAG, except for L. monocytogenes, where 40 min activation time and treatment time exceeding 20 min was required for significantly higher reduction to occur. PAN exhibited greater antibacterial activity at higher NaCl concentrations, which was attributed to increased ionic strength and reactive chlorine species. Additionally, we evaluated the microbial mechanisms of PAN by assessing cellular damage and alterations. The common observation across the three pathogens was that PAN resulted in increased cell membrane damage, reduced intermembrane enzyme activity, higher intracellular ROS levels, and changes in zeta potential values, while DNA damage was observed only in PAN-treated L. monocytogenes. Furthermore, when PAW and PAN were stored for up to four weeks, PAN showed higher efficacy compared to PAW. 10 % PAN was also effective against foodborne pathogens on mackerel, achieving log reductions of 3.62 for E. coli O157:H7, 4.62 for S. Typhimurium, and 3.18 for L. monocytogenes after a 20 min treatment without adversely affecting quality. Our results demonstrated the antibacterial activity and action mechanism of PAN, presenting its potential application in the seafood industry.

A cationic AIE luminutesogen TBPD2+-6C as a potential bacterial detection agent and bactericide for plants bacterium

The rise of plant bacterial pathogens poses a significant threat to the yield and quality of essential food crops and cash crops globally. Our research introduced a versatile cationic AIE fluorescent probe for detecting and eliminutesating plant bacteria. With its unique aggregation-induced emission property, TBPD2+-6C can effectively detect plant bacteria by causing a fluorescence quenching effect and enables bacterial imaging under green fluorescence channels. Additionally, TBPD2+-6C demonstrates outstanding antibacterial effectiveness, with EC50 values of 0.27, 3.86, 0.47, and 11.5 μg/mL against Xanthomonas oryzae pv. oryzicola (Xoc), X. oryzae pv. oryzae (Xoo), Pseudomonas syringae pv. actinidiae (Psa), and X. axonopodis pv. citri (Xac), respectively. In vivo testing against Xoc revealed TBPD2+-6C showed better activity than commercial thiodiazole copper (TC) and bismerthiazol (BT). Furthermore, the investigation into the antibacterial mechanism revealed that the cationic compound can effectively integrate into the bacterial membrane, disrupt the membrane structure, trigger ROS accumulation, and inhibit biofilm formation. In conclusion, the development of multifunctional, broad-spectrum antimicrobial system molecular designs for rapid real-time detection, imaging, and elimination of resistant microbes could play a vital role in combating pathogens.

New Insights into the Antibacterial Activity of Hydroxytyrosol Extracted from Olive Leaves: Molecular Docking Simulations of its Antibacterial Mechanisms.

This study investigated the biological activities of a hydroxytyrosol-rich extract from Olea europaea leaves, particularly its ability to eradicate severe pathogenic bacteria producing Extended-Spectrum Beta-Lactamases (ESBLs). The latter bacteria are emerging microorganisms that pose significant challenges due to their resistance to a broad range of potent therapeutic drugs. The extract was prepared through an accessible acid hydrolysis method. In vitro and In silico analyses through MIC, MBC analysis and molecular docking were conducted to evaluate the antibacterial properties. The extract showed remarkable antioxidant activity and significant antibacterial potential against reference species and ESBL bacteria. MIC and MBC calculations confirmed the extract's capacity to kill bacteria rather than just inhibit their growth. Further in silico analyzes demonstrated the high binding affinity of HT to the active sites of the gyrase B subunit and the peptidoglycan DD-transpeptidase domain from proteins located in the cytoplasm and the cell wall of the bacteria, respectively. Results confirmed the structure-activity relationship and the ability of HT to disrupt essential bacterial functions. This study validates the debated antimicrobial potential of HT and highlights its importance as a potential therapeutic agent against resistant bacteria, which is a critical area of research given the global challenge of antibiotic resistance.

Novel structural determinants and bacterial death-related regulatory effects of the scorpion defensin BmKDfsin4 against gram-positive bacteria

Numerous defensins constitute a family of cationic antimicrobial peptides with high degrees of sequence variability, and in-depth characterization of their structural basis and antibacterial mechanisms remains limited. Here, a representative scorpion defensin, BmKDfsin4, with two distinct hydrophobic and basic residue clusters, was extensively investigated. The hydrophobic residue cluster, formed by Phe2, Pro5, Phe6, Phe28 and Leu29 residues, strongly influences the antibacterial activity of BmKDfsin4 against Gram-positive bacteria. Compared with the three scattered Lys13, Lys30 and Arg32 residues, the basic residue cluster, consisting of the Arg19, Arg20, Arg21 and Arg37 residues, played a less important role. The synergistic interaction between the basic residue cluster and Arg32 significantly affected BmKDfsin4 function. The bacterial growth inhibition by BmKDfsin4 was associated with regulating expression levels of cell division-related genes, cell wall synthesis-related genes and bacterial autolysis-related genes rather than destroying the bacterial cell membrane. The coincubation of BmKDfsin4 with the bacterial strains induced gradual changes in the bacterial surface from a rough and thin surface to a noticeably wrinkled surface together with abundant white spots and even complete cavities within the bacteria. These findings revealed novel structural determinants and bacterial death-related regulatory effects of the defensin BmKDfsin4 and highlighted diverse antibacterial mechanisms of defensins.

Glucose-gated nanocoating endowing polyetheretherketone implants for enzymatic gas therapy to boost infectious diabetic osseointegration

The hyperglycemic micromilieu surrounding implants in diabetic patients leads to high failure rate of implantation and implant-associated infection. Carbon monoxide (CO) has been reported to combat infections; however, its on-demand liberation and the elucidation of the underlying antibacterial mechanism remain challenging. To address this issue, we develop a multipurpose orthopedic implant comprising polyetheretherketone, glucose oxidase (GOx), and manganese carbonyl nanocrystals (MnCO), serving as a glucose-gated nanocoating for enzymatic gas therapy to improve infectious diabetic osseointegration. The GOx acts as a glucose-actuated gate responsive to hyperglycemia, thereby delivering CO in situ triggered by the GOx-driven Fenton-like reaction of MnCO nanocrystals. The released CO considerably prevents bacterial multiplication by penetrating the membrane, binding to cytochrome bo3, and interfering with the respiratory chain in vitro. Furthermore, the engineered implant displays desired antibacterial properties and enhances osseointegration in vivo. Collectively, the orthopedic nanocoating implant is capable of delivering glucose-gated enzymatic gas therapy, promising for treating infectious diabetic bone defects.

A respiratory Streptococcus strain inhibits Acinetobacter baumannii from causing inflammatory damage through ferroptosis

BackgroundMicroecological equilibrium is essential for human health. Previous research has demonstrated that Streptococcus strain A, the main bacterial group in the respiratory tract, can suppress harmful microbes and protect the body. In this study, Streptococcus strain D19T was isolated from the oral and pharyngeal cavities of healthy children. Its antibacterial mechanism against Acinetobacter baumannii was examined, as well as its potential to prevent inflammatory damage to cells. We evaluated the effect of the fermentation conditions of D19T on inhibition of Acinetobacter baumannii growth; Isolation and purification of antibacterial active components of strain D19T and molecular mechanism of inhibition of Acinetobacter baumannii; Molecular mechanism of D19T antibacterial protein reversing cellular inflammatory injury induced by Acinetobacter baumannii.ResultsThe supernatant of fermentation broth of Streptococcus D19T was the active component against Acinetobacter baumannii, but the bacteria had no antibacterial activity. The supernatant of D19T fermentation broth was precipitated by (NH4)2SO4 solution, and the protein was the active antibacterial component. After gel filtration chromatography and anion gel filtration chromatography, the molecular weight of antibacterial protein was 53kD. D19T antibacterial protein can improve cell membrane permeability, limit extracellular soluble protein release, inhibit Acinetobacter baumannii biofilm formation, and prevent Acinetobacter baumannii adhesion. Acinetobacter baumannii induces inflammatory damage to respiratory cells via ferroptosis, and the D19T antibacterial protein can counteract this damage, protecting the respiratory tract.ConclusionStreptococcus strain D19T, as a potential probiotic, inhibits the growth of Acinetobacter baumannii and the inflammatory damage of respiratory cells, playing a protective role in human respiratory health.

Fabrication and characterization of new hot extruded ZK60/CNTs+AgNPs nanocomposites for biomedical applications

Magnesium (Mg), with properties such as biodegradability and having a density and elasticity coefficient close to the bones of the body, has attracted a lot of attention as a serious option for orthopedic applications. However, the low compressive strength of Mg compared to the human bone and its weak antibacterial function limit its applications as a substitute for temporary implants to be used under load-bearing conditions. The aim of this paper is to evaluate the synergistic effect of CNTs + AgNPs nanofillers on the in vitro degradation, mechanical and antibacterial behavior of new ZK60/xCNTs + xAgNPs(x: 0, 0.25, 0.5, 1) composites made using semi powder metallurgy, followed by hot extrusion method. The ZK60/0.5CNTs+0.5 AgNPs (CA2) composite boasts a higher ultimate compressive strength (UCS) of 371 ± 15 MPa compared to 297 ± 6 MPa for ZK60 based alloys. The CA2 composite also exhibits a grain size of 9.8 μm and a microhardness of 81 HV.Also, the antibacterial activity assessment demonstrated that adding CNTs + AgNPs hybrid nanofillers to the Mg matrix could notably prevent growing and penetration of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which indicates the synergy between antibacterial mechanisms of CNTs and AgNPs. Cytotoxicity studies confirm that composites with low amounts of CNTs + AgNPs did not show cytotoxic behavior against MG63 cells, although higher loading of CNTs + AgNPs caused toxicity. Also, the examination of osteogenic activity is consistent with other results. In general, according to the results, the potential application of CA2 composite for under load bearing implant application and bone infection treatment is proved.

Restoring Colistin Sensitivity in Multidrug-Resistant Pathogenic E. coli Using Cinacalcet Hydrochloride

Restoring colistin’s efficacy is crucial in addressing the resistance crisis of colistin. This study utilized a high-throughput screening method to identify 43 compounds from 800 FDA-approved drugs that exhibited significant antibacterial effects when combined with colistin. Among these, cinacalcet hydrochloride (CH) was selected for its potential synergistic effect with colistin against multidrug-resistant (MDR) E. coli strains, including mcr-1-positive strains. A series of experiments revealed that the combination of CH and colistin showed strong synergy, especially in mcr-1-positive strains, restoring colistin sensitivity. The combination significantly inhibited bacterial growth and reduced CFU counts more effectively than either drug alone. Additionally, CH and colistin together significantly inhibited biofilm formation and eradicated existing biofilms, as visualized through confocal microscopy. Mechanistic studies showed that the combination increased bacterial membrane permeability and disrupted membrane integrity. The treatment also elevated extracellular ATP release and ROS production, indicating oxidative stress-induced bacterial death. Safety evaluations showed that the combination did not increase toxicity in host cells. Finally, animal models further validated the combination’s efficacy. Overall, this study showed that the combination of colistin and CH significantly restored colistin sensitivity in mcr-1-positive E. coli, revealing their synergistic antibacterial mechanism involving membrane damage and oxidative stress, with promising clinical applications.

A Synergistic Interaction Between Citrus Hystrix Peel Essential Oil and Tetracycline and Evaluation of their Antibacterial Mechanism of Action in Vitro and in Silico Against Escherichia Coli.

Citrus hystrix essential oil (CHEO) have shown various pharmacological properties including antibacterial activity. This EO also possessed antibacterial effect against foodborne pathogens. There is less information available about the synergy interaction between CHEO and tetracycline, as well as their mechanism of action. Therefore, this study was conducted to evaluate the synergistic effect of CHEO and tetracycline against clinical isolate of Escherichia coli. Antibiofilm, bacteriolytic, and efflux pump inhibitor activities were also performed. The chemical composition of CHEO was analysed using GC-MS. Three major compounds, D-limonene (25.02 %), β-pinene (23.37 %), and β-sabinene (22.20 %) were identified. CHEO exhibited moderate antibacterial activity with MIC value of 250 μg/mL. The combination of CHEO (7.8 μg/mL) and tetracycline (62.5 μg/mL) produced a synergistic effect on E. coli with fractional inhibitory concentration index of 0.5. This mixture inhibited biofilm formation in E. coli. The combination of 7.8 μg/mL CHEO and 62.5 μg/mL tetracycline demonstrated bacteriolytic activity. In addition, the CHEO at 250 μg/mL showed a significant effect in inhibiting efflux pump. D-limonene has a binding free energy value of -20.13 kcal/mol with ompA transmembrane domain of E. coli. This finding indicates that CHEO has a potency to be developed as natural antibacterial against E. coli.

Imaging‐based profiling for elucidation of antibacterial mechanisms of action

AbstractIn this review, we aim to summarize experimental data and approaches to identifying cellular targets or mechanisms of action of antibacterials based on imaging techniques. Imaging‐based profiling methods, such as bacterial cytological profiling, dynamic bacterial morphology imaging, and others, have become a useful research tool for mechanistic studies of new antibiotics as well as combinations with conventional ones and other therapeutic options. The main methodological and experimental details and obtained results are summarized and discussed. The review covers the literature up to February 2024.

Recent Advances in the Preparation, Antibacterial Mechanisms, and Applications of Chitosan

Chitosan, a cationic polysaccharide derived from the deacetylation of chitin, is widely distributed in nature. Its antibacterial activity, biocompatibility, biodegradability, and non-toxicity have given it extensive uses in medicine, food, and cosmetics. However, the significant impact of variations in the physicochemical properties of chitosan extracted from different sources on its application efficacy, as well as the considerable differences in its antimicrobial mechanisms under varying conditions, limit the full realization of its biological functions. Therefore, this paper provides a comprehensive review of the structural characteristics of chitosan, its preparation methods from different sources, its antimicrobial mechanisms, and the factors influencing its antimicrobial efficacy. Furthermore, we highlight the latest applications of chitosan and its derivatives across various fields. We found that the use of microbial extraction shows promise as a new method for producing high-quality chitosan. By analyzing the different physicochemical properties of chitosan from various sources and the application of chitosan-based materials (such as nanoparticles, films, sponges, and hydrogels) prepared using different methods in biomedicine, food, agriculture, and cosmetics, we expect these findings to provide theoretical support for the broader utilization of chitosan.

Advances in Spiky Antibacterial Materials: From Bioinspired Design to Application

Bacterial infections, particularly those caused by drug‐resistant bacteria, pose a significant threat to human life and health safety. Despite the preparation and application of numerous antibacterial and disinfection materials, addressing their low efficiency and the emergence of drug resistance remains an urgent concern. Inspired by natural spike antibacterial structures such as those found on cicada wings, extensive research has been conducted on biomimetic antibacterial materials with spiky structures. This review provides an overview of the natural spike antibacterial structure and mechanism, introduces surface coatings and micro/nanoparticle materials featuring spike structures inspired by nature, explores microneedle arrays based on spike antibacterial properties, and showcases applications of these innovative antibacterial materials. Finally, potential avenues for optimization and future development directions for antibacterial materials with spike structures are discussed.

Microbial synthesis of zinc oxide nanoparticles and their potential biological application as an antimicrobial and anticancer agent

Zinc oxide nanoparticles (ZnO-NPs) are a type of metal oxide nanomaterial, recognized as a valuable and adaptable inorganic compound owing to its distinctive physical and chemical properties. Nanosized ZnO particles exhibit substantial antibacterial properties attributable to their diminutive size, which can activate various bactericidal mechanisms within the bacterial cell, including interactions with the bacterial surface or core, the generation of reactive oxygen species (ROS), the release of Zn2+, and potential endocytosis by cells. ZnO NPs nanoparticles were extracellularly produced using pigment extracts from the PP6 strain. Agar well screening indicated that PP6 secondary metabolites possess antibacterial properties. UV–Vis spectroscopy was used to analyze the external growth of nanoparticles. Scanning Electron Microcopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD) techniques were employed to analyze the shape, stability, crystalline structure, and coating of strain PP6 ZnO NPs. The PP6 ZnO NPs demonstrated an antibiofilm impact on the bacterial pathogens tested, which was dependent on the dosage. Elevated levels of lipid peroxidation (LPO) and reduced antioxidant activity are indicative of apoptosis in cancer cells. The synthesized ZnO NPs nanoparticles were assessed for their anticancer properties by performing the MTT assay on HT-29 human colorectal adenocarcinoma cells. ZnO NPs nanoparticles exposed to HT-29 cells the viability was reduced significantly in proportion to the concentration of nanoparticles. Additional comprehensive study will be needed to fully understand their mechanism.

Dodecanoyl-L-tryptophan: A Novel Natural Antibiotic Isolated from Mesophotic Sponge-associated Salinicola sp. LHM and its Biological Function

Background: Sponge-associated microbiota plays a crucial role in maintaining host health by providing chemical defense through the synthesis of diverse secondary metabolites. However, research on these secondary metabolites is still in its early stages. Objective: The present study aimed to investigate new natural antibiotics from mesophotic sponge symbiotic microbiota and explore its in vitro antibacterial activity and preliminary biological function. Methods: Bacteria strain Salinicola sp. LHM was isolated from sponge L. birotulata L26 and identified based on the 16S rRNA gene analysis. Subsequently, the strain was fermented using a liquid M9 medium and screened for antibiotics with an antibacterial guiding assay. Extensive chromatographic methods were introduced to isolate the target compound, and its chemical structure was elucidated by spectroscopic analysis (LC-MS, NMR). The minimum inhibitory concentration (MIC) and cytotoxicity experiments evaluated the isolated compound's biological activity. Furthermore, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quartz crystal microbalance with dissipation (QCM-D) were used to study the bactericidal mechanism of DLT. Finally, the preliminary biological function was explored by performing the cell-feeding experiment. Results: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. result: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. Conclusion: This research identified one novel natural antibiotic DLT and provided initial insights into the chemical defense exerted by Salinicola sp. LHM with its secondary metabolite DLT.

Antibacterial effects and mechanisms of quercetin-β-cyclodextrin complex mediated photodynamic on Escherichia coli O157:H7.

Quercetin is a natural flavonoid with antioxidant, anti-inflammatory, and antibacterial properties. This work aimed to formulate quercetin-cyclodextrin microcapsules (QT-β-CD) while examining their photodynamic antibacterial effects and underlying mechanisms in detail. Characterization of the QT-β-CD was conducted using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The bacteriostatic effects of UV-A irradiation on Escherichia coli O157:H7 (E. coli O157:H7) were investigated. The photodynamic impact of QT-β-CD was assessed by analyzing hydrogen peroxide (H₂O₂) production. The antimicrobial activity was further elucidated through examinations of cell membrane integrity, protein damage, changes in cellular motility, biofilm formation, and extracellular polysaccharide reduction. The effect of QT-β-CD on LuxS and motA gene expression in E. coli O157:H7 was investigated by RT-qPCR. The findings demonstrated that QT-β-CD exhibited potent photodynamic properties and functioned as an efficient photosensitizer, causing substantial damage to E. coli O157:H7 cells. These results underscore the potential of quercetin as an antimicrobial agent for food preservation.

Colistin-niclosamide-loaded nanoemulsions and nanoemulsion gels for effective therapy of colistin-resistant Salmonella infections.

Colistin (COL) is regarded as a last-resort treatment for infections by multidrug-resistant (MDR) Gram-negative bacteria. The emergence of colistin-resistant Enterobacterales poses a significant global public health concern. Our study discovered that niclosamide (NIC) reverses COL resistance in Salmonella via a checkerboard assay. However, poor solubility and bioavailability of NIC pose challenges. In this study, we prepared a self-nanoemulsifying drug delivery system (SNEDDS) co-encapsulating NIC and COL. We characterized the physicochemical properties of the resulting colistin-niclosamide-loaded nanoemulsions (COL/NIC-NEs) and colistin-niclosamide-loaded nanoemulsion gels (COL/NIC-NEGs), assessing their antibacterial efficacy in vitro and in vivo. The COL/NIC-NEs exhibited a droplet size of 19.86 nm with a zeta potential of -1.25 mV. COL/NIC-NEs have excellent stability, significantly enhancing the solubility of NIC while also demonstrating a pronounced sustained-release effect. Antimicrobial assays revealed that the MIC of COL in COL/NIC-NEs was reduced by 16-128 times compared to free COL. Killing kinetics and scanning electron microscopy confirmed enhanced antibacterial activity. Antibacterial mechanism studies reveal that the COL/NIC-NEs and COL/NIC-NEGs could enhance the bactericidal activity by damaging cell membranes, disrupting proton motive force (PMF), inhibiting multidrug efflux pump, and promoting oxidative damage. The therapeutic efficacy of the COL/NIC-NEs and COL/NIC-NEGs is further demonstrated in mouse intraperitoneal infection models with COL-resistant Salmonella. To sum up, COL/NIC-NEs and COL/NIC-NEGs are a potentially effective strategies promising against COL-resistant Salmonella infections.