Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.
Hypsizygus marmoreuss is an under-explored source of flavor peptides that can enhance the flavor of NaCl or MSG, allowing products to be reformulated in line with reduction policies. This study utilized advanced techniques, including UPLC-Q-TOF MS/MS and molecular docking, to identify H. marmoreuss peptides. Sensory evaluations revealed 10 peptides with pronounced umami flavors and seven with dominantly salty tastes. VLPVPQK scored highest for umami intensity (5.2), and EGNPAHQK for salty intensity (6.2). Further investigation influenced by 0.35 % MSG or 0.35 % NaCl exposed peptides with elevated umami and salty thresholds. LDSPATPEK, VVEGEPSLK, and QKLPEKPER had umami-enhancing thresholds of 0.18, 0.18, and 0.35 mM, while LDSPATPEK and VVEGEPSLK had similar thresholds for salt (0.09 mM). Molecular docking revealed that taste receptor proteins interacted with umami peptides through hydrogen, carbon-hydrogen, alkyl, and van der Waals forces. Specific amino acids in the umami receptor T1R1 had roles in bonding with umami peptides through hydrogen and carbon-hydrogen interactions. In conclusion, molecular docking proved to be an effective and efficient method for flavor peptide screening. Further, this study demonstrated that flavor peptides from H. marmoreuss had the capacity to enhance NaCl and MSG flavours and might be useful tools for reformulation, reducing salt and MSG contents.
Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO4 via induing hallmarks of ferroptosis, including Fe2+ overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO4 disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO4-loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO4 as an innovative strategy in treating C. albicans infections by targeting ferroptosis.
Candidiasis, Vulvovaginal , Ferroptosis , Ferrous Compounds , Humans , Female , Animals , Mice , Candidiasis, Vulvovaginal/drug therapy , Candidiasis, Vulvovaginal/microbiology , Candida albicans/genetics , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Hydrogels/therapeutic use , Microbial Sensitivity Tests
Ready-to-eat kiwifruit has gained significant market value in recent years due to its convenience and the increasing consumer demand for healthy ready-to-eat snacks. The volatile compound content (VOC) in ready-to-eat kiwifruit is a crucial factor determining its flavor and aroma. VOC is an important characteristic that positively affects the overall evaluation of ready-to-eat kiwifruit. In this study, we utilized gas chromatography-ion mobility spectrometry (GC-IMS) to investigate changes in the composition of VOCs in ready-to-eat kiwifruit during different storage periods (every 12 h). Our results revealed the presence of 55 VOCs in ready-to-eat kiwifruit, with alcohols, esters, and ketones being the dominant compounds responsible for the aromatic flavor. Among these compounds, methyl caproate, ethyl butyrate, and ethyl propionate provided specific fruit flavors to ready-to-eat kiwifruit, whereas esters played a secondary role. Furthermore, varying trends were observed for different compound types as the storage period increased: alcohols exhibited a decreasing trend, whereas ester products and some sulfur-containing compounds showed an increase. Additionally, fingerprint profiles of volatile compounds were established for each storage period, enabling the identification of characteristic substances. This comprehensive analysis of volatile flavor substances during the ripening of ready-to-eat kiwifruit will greatly contribute to enhancing its sensory quality, consumer appeal, and overall marketability.
Pickering emulsion gel (PEG) stabilized by the protein extracted from the by-product of Hypsizygus marmoreus, combining with xanthan gum (XG), was formulated as 3D printing ink. Hydrogen bonds are formed in XG/protein hybrid particles. Afterwards, PEG was developed. Results indicated that it has shear-thinning properties. The apparent viscosity, yield stress, Elastic modulus (G') and gel strength increased with the increased XG addition, while the size of emulsion decreased. XG incorporation improved the 3D printing performance with desired self-supporting capability and printing precision if its concentration reached 2.0% (w/v). This study provides ideas for the application of Hypsizygus marmoreus by-products protein in stabilizing PEG used for 3D printing, which has a potential to replace traditional hydrogenated cream for cake decoration.
Aflatoxin B1 (AFB1), as a class I carcinogen, poses a substantial health risk to individuals. Contamination of food sources, particularly grains and nuts, with Aspergillus flavus (A. flavus) contributes to the prevalence of AFB1. The impact of global warming has spurred research into the development of AFB1 prevention technologies. While edible fungi have shown potential in detoxifying AFB1, there is a scarcity of literature on the application of Auricularia auricular (A. auricular) in this context. This study aimed to investigate the ability and underlying mechanism of A. auricular mycelia to adsorb aflatoxin B1, as well as evaluate its protective effects on the AFB1-induced liver damage in SD rats. Additionally, the effects of temperature, time, pH, and reaction ratio on the adsorption rate were examined. Combining thermodynamic and kinetic data, the adsorption process was characterized as a complex mechanism primarily driven by chemical adsorption. In SD rats, the A. auricular mycelia exhibited alleviation of AFB1-induced liver damage. The protective effects on the liver attributed to A. auricular mycelia may involve a reduction in AFB1 adsorption in the intestine, mitigation of oxidative stress, and augmentation of second-phase detoxification enzyme activity. The adsorption method for AFB1 not only ensures safety and non-toxicity, but also represents a dietary regulation strategy for achieving effective defense against AFB1.
The increasing incidence of diseases caused by highly carcinogenic aflatoxin M1 (AFM1) in food demands a simple, fast, and cost-effective detection technique capable of sensitively monitoring AFM1. Recent works predominantly focus on the electrochemical aptamer-based biosensor, which still faces challenges and high costs in experimentally identifying an efficient candidate aptamer. However, the direct electrochemical detection of AFM1 has been scarcely reported thus far. In this study, we observed a significant influence on the electrochemical signals of ferric ions at a gold nanoparticle-modified glassy carbon electrode (AuNPs/GCE) by adding varying amounts of AFM1. Utilizing ferricyanide as a sensitive indicator of AFM1, we have introduced a novel approach for detecting AFM1, achieving an unprecedentedly low detection limit of 1.6 × 10-21 g/L. Through monitoring the fluorescence quenching of AFM1 with Fe3+ addition, the interaction between them has been identified at a ratio of 1:936. Transient fluorescence analysis reveals that the fluorescence quenching process is predominantly static. It is interesting that the application of iron chelator diethylenetriaminepentaacetic acid (DTPA) cannot prevent the interaction between AFM1 and Fe3+. With a particle size distribution analysis, it is suggested that a combination of AFM1 and Fe3+ occurs and forms a polymer-like aggregate. Nonetheless, the mutual reaction mechanism between AFM1 and Fe3+ remains unexplained and urgently necessitates unveiling. Finally, the developed sensor is successfully applied for the AFM1 test in real samples, fully meeting the detection requirements for milk.
Spicy wheat flour gluten sticks are delicious and affordable puffed snacks for young adults and even minors in China, and have a relatively simple nutritional quality. L. edodes powder (LEP) is rich in nutrients and boasts a variety of biological activities. This study evaluated the effects of different concentrations of LEP addition on the quality of wheat flour gluten sticks. The gelatinization results of the products showed that the peak viscosity decreased from 454 cP to 251 cP; the breakdown value decreased from 169 cP to 96 cP; and the setback value decreased from 381 cP to 211 cP. With the increase in LEP, the radial expansion rate (RER) of L. edodes gluten sticks (LSGS) first increased and then decreased, reaching a maximum value of 1.388 in the 10% LEP group. The oil absorption rate (OAR) of LSGS increased from 5.124% to 14.852% with the increase in the amount of LEP. Additionally, texture profile analysis showed that the hardness value increased from 1148.898 to 2055.492 g; the chewiness value increased from 1010.393 to 1499.233; and the springiness value decreased from 1.055 to 0.612. Through X-ray diffraction (XRD), it was found that the crystal type was transformed from A-type crystal to B-type and V-type crystals. Low field nuclear magnetic resonance (LF-NMR) results showed that the moisture distribution in the products was basically bound water. The scanning electron microscopy (SEM) results showed that, with the increase in the LEP amount, the surface of the products changed from rough to smooth. Sensory evaluation results indicated that the products with 10% LEP helped to maintain better taste and quality of LSGS, with an average score of 7.628, which was the most popular among consumers. This study not only increases the possible raw materials for use in extruded puffed food, but also provides a new possibility for the production of high-quality edible fungi extruded products.
Vibrio parahaemolyticus is a typical marine bacterium, which often contaminates seafood and poses a health risk to consumers. Some non-thermal sterilization technologies, such as ultrasonic field (UF) and blue light (BL) irradiation, have been widely used in clinical practice due to their efficiency, safety, and avoidance of drug resistance, but their application in food preservation has not been extensively studied. This study aims to investigate the effect of BL on V. parahaemolyticus in culture media and in ready-to-eat fresh salmon, and to evaluate the killing effectiveness of the UF combined with BL treatment on V. parahaemolyticus. The results showed that BL irradiation at 216 J/cm2 was effective in causing cell death (close to 100%), cell shrinkage and reactive oxygen species (ROS) burst in V. parahaemolyticus. Application of imidazole (IMZ), an inhibitor of ROS generation, attenuated the cell death induced by BL, indicating that ROS were involved in the bactericidal effects of BL on V. parahaemolyticus. Furthermore, UF for 15 min enhanced the bactericidal effect of BL at 216 J/cm2 on V. parahaemolyticus, with the bactericidal rate of 98.81%. In addition, BL sterilization did not affect the color and quality of salmon, and the additive UF treatment for 15 min did not significant impact on the color of salmon. These results suggest that BL or UF combined with BL treatment has potential for salmon preservation, however, it is crucial to strictly control the intensity of BL and the duration of UF treatment to prevent reducing the freshness and brightness of salmon.
Vibrio parahaemolyticus , Animals , Salmon/microbiology , Reactive Oxygen Species , Seafood , Anti-Bacterial Agents/pharmacology
Benzyl isothiocyanate (BITC) is an isothiocyanate of plant origin, especially the mustard family, which has good antibacterial properties. However, its applications are challenging due to its poor water solubility and chemical instability. We used food hydrocolloids, including xanthan gum, locust bean gum, konjac glucomannan, and carrageenan as three-dimensional (3D)-printing food ink base and successfully prepared 3D-printed BITC antibacterial hydrogel (BITC-XLKC-Gel). The characterization and fabrication procedure of BITC-XLKC-Gel was studied. The results show that BITC-XLKC-Gel hydrogel has better mechanical properties by low-field nuclear magnetic resonance (LF-NMR), mechanical properties, and rheometer analysis. The strain rate of BITC-XLKC-Gel hydrogel is 76.5%, which is better than that of human skin. Scanning electron microscope (SEM) analysis showed that BITC-XLKC-Gel has uniform pore size and provides a good carrier environment for BITC carriers. In addition, BITC-XLKC-Gel has good 3D-printing performance, and 3D printing can be used for customizing patterns. Finally, inhibition zone analysis showed that the BITC-XLKC-Gel added with 0.6% BITC had strong antibacterial activity against Staphylococcus aureus and the BITC-XLKC-Gel added with 0.4% BITC had strong antibacterial activity against Escherichia coli. Antibacterial wound dressing has always been considered essential in burn wound healing. In experiments that simulated burn infection, BITC-XLKC-Gel showed good antimicrobial activity against methicillin-resistant S. aureus. BITC-XLKC-Gel is a good 3D-printing food ink attributed to strong plasticity, high safety profile, and good antibacterial performance and has great application prospects.
The abuse of chrome tanning agent in leather processing has caused great harm to human health and the natural environment. We use tremella polysaccharides (TP), lentinan (LNT) and konjac gum (KG) as raw materials, and sodium periodate as oxidant to prepare the corresponding polysaccharide tanning agent. Tremella polysaccharide was selected as the best tanning agent according to the shrinkage temperature, and the subsequent experiments were carried out. Tremella polysaccharide (TP) as raw material and sodium periodate as an oxidant, dialdehyde tremella polysaccharide (DTP) was prepared and applied in leather tanning. The effects of different oxidation conditions (sodium periodate dosage, temperature, pH, and reaction time) on the shrinkage temperature of DTP tanned leather were studied. The change of shrinkage temperature showed that the dosage of sodium periodate had the greatest influence on the shrinkage temperature. Therefore, the effects of different dosage of sodium periodate on the aldehyde content and molecular weight of DTP were investigated, including the analysis of physical properties and microstructure of tanned leather. In general, the increase of sodium periodate dosage was found to increase the aldehyde content and reduce the molecular weight, which was more conducive to leather tanning.
Polysaccharides , Tanning , Humans , Aldehydes , Oxidants , Chromium/analysis
Microbial pollution and fat oxidation are the main factors that induce the deterioration in the quality of chilled fresh mutton. This study evaluated the effects of cumin (Cuminum cyminum) essential oil (CEO), Zanthoxylum essential oil (ZEO), and blended cumin/zanthoxylum essential oil (BEO) on the antibacterial, preservation of freshness, and flavor improvement of chilled fresh mutton. The results show that BEO exerts a good inhibition effect on microbial growth, lipid oxidation, and the formation of TVB-N, as well as slowing down the rate of juice loss under chilled conditions. GC-IMS assay results showed that BEO can enrich the flavor of roasted mutton with a higher level of volatile organic substances, such as ethyl acetate D. In conclusion, BEO treatments were more efficient than single treatments in ensuring the quality of lamb to improve microbiological safety and improve the flavor of roasted lamb stored under chilled conditions. Overall research indicates that BEO is an effective natural addition that can be used to preserve the quality and safety of chilled fresh mutton during storage.
Cuminum , Oils, Volatile , Red Meat , Zanthoxylum , Animals , Anti-Bacterial Agents/pharmacology , Oils, Volatile/pharmacology , Oxidation-Reduction , Sheep
BACKGROUND: Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human infection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa. METHODS: Inspired by ferroptosis, the antibacterial effects of iron compounds on P. aeruginosa via direct exposure were investigated. In addition, thermal-responsive hydrogels to carry FeCl3 were developed as a wound dressing to treat P. aeruginosa-induced wound infection in a mouse model. RESULTS: The results showed that 200 µM FeCl3 killed more than 99.9% of P. aeruginosa cells. FeCl3-mediated cell death in P. aeruginosa was associated with hallmarks of ferroptosis in mammalian cells, including reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe2+ chelator alleviated FeCl3-mediated cell death, indicating that H2O2 and labile Fe2+ induced the Fenton reaction leading to cell death. Further proteomics analysis showed that proteins related to glutathione (GSH) synthesis and the glutathione peroxidase (GPX) family were significantly downregulated after FeCl3 treatment, which is equivalent to GPX4 inactivation in mammalian cells. The therapeutic effect of FeCl3 on P. aeruginosa was further evaluated in a mouse wound infection model using polyvinyl alcohol-boric acid (PB) hydrogels as a carrier of FeCl3. FeCl3-PB hydrogels completely cleared pus on wounds and promoted wound healing. CONCLUSION: These results indicated that FeCl3 induces microbial ferroptosis in P. aeruginosa and has high therapeutic potential for the treatment of P. aeruginosa wound infection.
Ferroptosis , Wound Infection , Mice , Animals , Humans , Pseudomonas aeruginosa , Hydrogen Peroxide/pharmacology , Wound Infection/drug therapy , Wound Healing , Glutathione/pharmacology , Hydrogels/pharmacology , Mammals
Numerous counterfeit vintage Baijiu are widely distributed in the market driven by economic interest which disturb the market economic rules and damage the reputation of particular Baijiu brand. Found on the situation, the Baijiu system variation during aging period, aging mechanisms and discrimination strategies for vintage Baijiu are systematically illuminated. The aging mechanisms of Baijiu cover volatilization, oxidation, association, esterification, hydrolysis, formation of colloid molecules and catalysis by metal elements or other raw materials dissolved from storage vessels. The discrimination of aged Baijiu has been performed by electrochemical method, colorimetric sensor array or component characterization coupled with multivariate analysis. Nevertheless, the characterization of non-volatile compounds in aged Baijiu is deficient. Further research on the aging principles, more easy-operation and low-cost discrimination strategies for aged Baijiu are imperative. The above information is favorable to better understand the aging process and mechanisms of Baijiu, and promote the development of artificial aging techniques.
Pickering emulsion based on OSA-starch was developed in this study as an intelligent delivery system for the application of thymol against foodborne pathogens. Morphology and microstructure characterization showed that the Pickering emulsion was an O/W type emulsion and stayed stable at starch concentration of 200 mg/mL and oil fraction at 30 % with particle size of 10 µm and absolute Zeta potential of -12.5 mV. Low field nuclear magnetic resonance and rheology experiments indicated that a denser network structure was formed in this stable Pickering emulsion. Besides, the Pickering emulsion could endure long-time storage, low pH (3,5) and additional NaCl (50, 100, 200, 400 mM) and it showed enhanced bactericidal effects against Escherichia coli, Staphylococcus aureus (thymol =1.48 µmol/L) and Aspergillus flavus (thymol = 0.624 µmol/L) by inducing ROS eruption, membrane lipid peroxidation and cell shrink. Moreover, the bactericidal assay demonstrated that thymol could be intelligently released and a considerable 75 % timely bactericidal effect was detected after 9 days' intermittently exposing to E. coli, S. aureus and A. flavus in vitro, by comparison thymol alone showed only 20 % bactericidal effect due to its volatility. The results are of great importance to offer an intelligent delivery system of bio-actives defending foodborne pathogens.
Anti-Bacterial Agents , Thymol , Anti-Bacterial Agents/pharmacology , Emulsions/chemistry , Escherichia coli , Particle Size , Staphylococcus aureus , Starch/chemistry , Thymol/pharmacology , Thymol/chemistry
Listeria monocytogenes frequently causes Listeriosis in humans and animals. In present study, we discovered that in the presence of FeSO4, L. monocytogenes became viable but non-culturable (VBNC), and remained virulent to Caenorhabditis elegans. The killing assay indicated that these VBNC cells kept sensitive to tetracycline, differing from dormant cells. Transcriptomic analysis revealed more gene transcription occurrence in the VBNC cells compared to dormant cells, involving stress response and ribosome binding. No ferroptosis hallmarks were observed in the VBNC cells, whereas the application of either intracellular Fe2+ chelator or the ferroptosis inhibitor arrested the formation of VBNC state by FeSO4, as well as by Benzakonium chloride or Haz-Tab. This implicated the universal involvement of intracellular Fe2+ and other cascades related to ferroptosis in the formation of VBNC state in L. monocytogenes. Taken together, we discovered an iron-induced VBNC state in L. monocytogenes, and provided clues to further understanding their potential risks.
Listeria monocytogenes , Listeriosis , Humans , Animals , Listeria monocytogenes/genetics , Anti-Bacterial Agents/pharmacology
Different xanthan gum (XG) concentrations on the rheological/texture properties of Pickering emulsion (PE) gel stabilized by tea protein/xanthan gum (TP/XG) were studied to achieve an ink feasible for 3D printing. Afterwards, the effects of 3D printing and digestion process on the viability of probiotics were studied when encapsulated in the PE gel. Results indicated that gel strength, stability, storage modulus (G') and loss modulus (Gâ³) increased as XG concentration increased. Nozzle diameter and printing temperature of 45 and 55â had no significant effect on probiotic's viability, but printing temperature of 65â reduced viable probiotics from 8.07 to 6.59 log CFU/g. No significant change of probiotics viability in 3D printed samples was observed during 11-day storage at 4â. PE gel encapsulated probiotic's viability was significantly improved under heat treatment and simulated gastrointestinal environment. This study gives insights on the production of 3D printed foods using PE gel incorporating probiotics.
Polysaccharides, Bacterial , Printing, Three-Dimensional , Emulsions , Tea , Rheology
Benzyl isothiocyanate (BITC) is widely utilized in multiple biomedical fields, due to its significant antibacterial properties and low toxicity. However, poor water solubility and pungent odor has limited its application in the food industry. In this study, we first prepared inclusion complexes of BITC in GLU-ß-CD and HP-ß-CD using ultrasound, which is able to overcome the hindrance of poor water solubility and high volatility. Then, the BITC-ß-CD inclusion complexes were characterized by using high-performance liquid chromatography (HPLC), nuclear magnetic resonance hydrogen spectra (1H-NMR), infrared absorption spectra (IR), and differential scanning calorimetry (DSC) to confirm their stability. Further, the evaluation of antibacterial and antitumor effects of the BITC-ß-CD inclusion complexes showed that they had great bactericidal activity against both Escherichia coli and Staphylococcus aureus cells, and also inhibited the growth of HepG2 cells in vitro. In addition, our results indicated that BITC-ß-CD complexes were able to inhibit the growth of S. aureus in broccoli juice and extend the shelf life of broccoli juice, demonstrating the potential of ß-cyclodextrin to improve the stability and controlled release of BITC. Taken together, our results show that BITC-ß-CD complexes have good potential for application in the food industry.
The objective of the current study was to evaluate the feasibility of papery food with Pleurotus eryngii (P. eryngii) as a raw material using the papermaking process. The physical, chemical, structural, and thermal degradation properties were studied as well as the sensory evaluation of the papery food from P. eryngii mycelia (PMP), stems (PSP), caps (PCP), and whole fruiting bodies (PEP). The results indicated that the colors from PSP, PCP, and PEP were clearly different from PMP. Thicker PSP and PMP had a smoother surface and better crispness compared to PCP. Moreover, PSP had better moisture resistance and thermal decomposition performance compared to the other groups. Nutritional composition and Fourier-transform infrared spectroscopy suggested abundant polysaccharide and protein content in all of the papery food. Finally, sensory evaluation showed that the formability, mouth feel, and overall palatability of PSP and PMP were more popular among consumers. Overall, this study provides a novel method for the preparation of papery food and provides a potential new mechanism for the further development and utilization of the fruiting bodies and mycelium of P. eryngii.
Hydrogels loaded with ampicillin, vancomycin or other antibiotics are one of the most widely used therapeutic agents for keratitis caused by Staphylococcus aureus. However, emergence of methicillin-resistant S. aureus (MRSA) makes infections harder to be treated by antibiotic-based hydrogels, urging the development of novel antibacterial materials. Inspired by mammalian ferroptosis, we determined the bactericidal effects of ferrous sulfate (FeSO4) on S. aureus, and evaluated the therapeutic potential of FeSO4-loaded hydrogel in a mouse keratitis model. The results showed that FeSO4 facilitated ferroptosis-like cell death in S. aureus with the key characteristics of reactive oxygen species (ROS) generation and lipid peroxidation. Notably, FeSO4 also efficiently killed persisters and MRSA, and eliminated biofilms of S. aureus. RNA profiles demonstrated that ferroptosis-related genes were significantly up-regulated, and the genes responsible for cell wall and cell membrane biosynthesis were down-regulated after exposure to Fe2+, supporting the occurrence of ferroptosis and cell lysis. We further prepared a FeSO4-loaded hydrogel by using hyaluronic acid (HA) and ascorbate. The FeSO4 hydrogel has the characteristics of injectability, self-healing, uniform distribution of Fe2+ in the three-dimensional gel structure, appropriate fluidity, high-water retention, high efficacy to kill MRSA, and excellent biocompatibility. In a mouse keratitis model, we showed that treatment of animals with FeSO4 hydrogel led to a rapid recovery of from keratitis, prevented the dissimilation of MRSA to the lung, and alleviated systemic inflammation, demonstrating the therapeutic potential of FeSO4 hydrogel. Taken together, our results indicated that FeSO4 hydrogel is a promising alternative to current antibiotics-dependent therapeutic materials for the treatment of infections by MRSA.
Ferroptosis , Keratitis , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Mice , Animals , Staphylococcus aureus , Methicillin-Resistant Staphylococcus aureus/physiology , Hydrogels/therapeutic use , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Keratitis/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/chemistry , Mammals
