Food Bioscience
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2023
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IF 5.2
Jinming Dai,Mei Bai,Changzhu Li,Wai San Cheang,Haiying Cui,Lin Lin
Citral, a natural antimicrobial agent, has been found to induce severe membrane damage resulting in bacterial death. Despite its effectiveness, there is a lack of in-depth research on its interaction with bacterial cells, especially at low concentrations. This work aimed to investigate the impact of citral concentration on its antibacterial effect against Staphylococcus aureus ( S. aureus ) and to analyze the relevance between membrane damage and cell death. In this study, the minimal inhibitory concentration of citral against S. aureus was measured at 0.25 mg/mL. At a concentration of 0.5 mg/mL, citral significantly disturbed the cell membrane fluidity and permeability, leading to the leakage of intracellular macromolecules and rapid cell death. However, when the concentration was decreased to 0.25 mg/mL, the membrane damage was greatly reduced, and a complex biological process between citral and membrane components was found. Under continuous drug exposure, the cell membrane underwent gradual rigidification, concomitant with the loss of membrane function, ultimately causing cell death. Despite the fact that no notable disturbance to membrane functions was discovered, the presence of 0.125 mg/mL citral could still weaken the metabolic vitality and growth of S. aureus . Therefore, it was suggested that there could be multiple mechanisms of citral action on S. aureus cells, with drug concentration being a critical factor affecting the mode of action. Overall, the findings of this study provide valuable insights into the antibacterial mechanisms of natural compounds and broaden the potential applications of citral as a natural antimicrobial.
研究领域:
微生物学
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药理学
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天然产物研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
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2023
·
IF 4.1
Shasha Liu,Pengfei She,Zehao Li,Yimin Li,Linhui Li,Yifan Yang,Linying Zhou,Yong Wu
There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we repurposed hexestrol (HXS) as an antibacterial agent to fight planktonic and biofilm-related MRSA infections. HXS is a nonsteroidal synthetic estrogen that targets estrogen receptors (ERα and ERβ) and has been used as a hormonal antineoplastic agent. In our work, the minimum inhibitory concentrations (MICs) were determined using the antimicrobial susceptibility of MSSA and MRSA strains. Anti-biofilm activity was evaluated using biofilm inhibition and eradication assays. Biofilm-related genes were analyzed with or without HXS treatment using RT qPCR analysis of S. aureus . HXS was tested using the checkerboard dilution assay to identify antibiotics that may have synergistic effects. Measurement of ATP and detection of ATPase allowed the determination of bacterial energy metabolism. As shown in the results, HXS showed effective antimicrobial activity against S. aureus , including both type strains and clinical isolations, with MICs of 16 µg/mL. Sub-HXS strongly inhibited the adhesion of S. aureus . The content of extracellular polymeric substances (EPS) and the relative transcription levels of eno , sacC , clfA , pls and fnbpB were reduced after HXS treatment. HXS showed antibacterial effects against S. aureus and synergistic activity with aminoglycosides by directly interfering with cellular energy metabolism. HXS inhibits adhesion and biofilm formation and eradicates biofilms formed by MRSA by reducing the expression of related genes. Furthermore, HXS increases the susceptibility of aminoglycosides against MRSA. In conclusion, HXS is a repurposed drug that may be a promising therapeutic option for MRSA infection.
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
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IF 10.7
Xilong Cui,Fanhui Liu,Shuang Cai,Tingting Wang,Sidi Zheng,Xinshu Zou,Linlin Wang,Siqi He,Yanhua Li,Zhiyun Zhang
The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-D-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99%) reduction of biofilm MRSA as compared to untreated wound ( P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
研究领域:
纳米技术
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药学
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微生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 11
·2614
·
IF 4.35
Qing-Hui Wen,Rui Wang,Si-Qi Zhao,Bo-Ru Chen,Xin-An Zeng
Taking into consideration the importance of biofilms in food deterioration and the potential risks of antiseptic compounds, antimicrobial agents that naturally occurring are a more acceptable choice for preventing biofilm formation and in attempts to improve antibacterial effects and efficacy. Citrus flavonoids possess a variety of biological activities, including antimicrobial properties. Therefore, the anti-biofilm formation properties of the citrus flavonoid naringenin on theStaphylococcus aureusATCC 6538 (S. aureus) were investigated using subminimum inhibitory concentrations (sub-MICs) of 5~60 mg/L. The results were confirmed using laser and scanning electron microscopy techniques, which revealed that the thick coating ofS. aureusbiofilms became thinner and finally separated into individual colonies when exposed to naringenin. The decreased biofilm formation ofS. aureuscells may be due to a decrease in cell surface hydrophobicity and exopolysaccharide production, which is involved in the adherence or maturation of biofilms. Moreover, transcriptional results show that there was a downregulation in the expression of biofilm-related genes and alternative sigma factorsigBinduced by naringenin. This work provides insight into the anti-biofilm mechanism of naringenin inS. aureusand suggests the possibility of naringenin being used in the industrial food industry for the prevention of biofilm formation.Keywords:naringenin;biofilm formation;cell surface hydrophobicity;confocal laser scanning microscopy;biofilm-related genes
研究领域:
食品科学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2021
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IF 4.952
Hui Li,Mao Zhang,Keren Agyekumwaa Addo,Yigang Yu,Xinglong Xiao
The antibacterial mechanisms of cuminaldehyde ( p -Isopropylbenzaldehyde, CUM) against Staphylococcus aureus ATCC 6538 ( S. aureus ) were investigated from the aspects of membrane damage, and interaction with genomic DNA. The results demonstrated that the MIC of CUM against S. aureus was 0.8 μL/mL. Approximately 6 log CFU/mL of S. aureus could be killed after treatment with MIC of CUM after 8 h. Additionally, CUM increased the permeability of the cell membrane by inducing visible changes in cell morphology. The results of gel electrophoresis, spectroscopic analysis, and molecule docking indicated that CUM could bind to DNA through groove mode and change the secondary structure of DNA, and ultimately lead to the inactivation of cells. Compared with untreated samples, application of CUM (2 or 4 MIC) on sauced beef caused an obvious decrease in S. aureus counts and effectively inhibited the growth of S. aureus . Moreover, CUM at a concentration of 2 MIC had no significant effect on the taste and aroma score of sauced beef. Therefore, CUM could play a dual antibacterial effect by influencing cell membrane and genomic DNA, and controlling the growth of S. aureus in the food industry.
研究领域:
食品科学
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微生物学
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产品关联
DOI
高影响因子
RSC Advances
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2019
·Vol. 9
·期 7
·3938-3945
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IF 3.049
Jin-Rong Bai,Yan-Ping Wu,Grosu Elena,Kai Zhong,Hong Gao
The biofilm formation of Staphylococcus aureus on food contact surfaces is the main risk of food contamination. In the present study, we firstly investigated the inhibitory effect of quinic acid (QA) on biofilm formed by S. aureus. Crystal violet staining assay and microscopy analysis clearly showed that QA at sub-MIC concentrations was able to significantly reduce the biofilm biomass and cause a collapse on biofilm architecture. Meanwhile, fibrinogen binding assay showed that QA had obviously effect on the S. aureus bacteria adhesion. XTT reduction assay and confocal laser scanning microscopic images revealed that QA significantly decreased metabolic activity and viability of biofilm cells. In addition, qRT-PCR analysis explored the potential inhibitory mechanism of QA against biofilm formation, which indicated that QA significantly repressed the gene sarA and activated the gene agrA. Moreover, QA exhibited a highly ability to reduce the number of sessile S. aureus cells adhered on the stainless steel. So, it was suggested that QA could be used as a promising antibiofilm agent to control biofilm formation of S. aureus.
研究领域:
微生物学
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食品安全
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分子生物学
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DOI
PubMed
高影响因子
TOXICON
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2022
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IF 3.035
Mao Zhang,Hui Li,Addo Keren Agyekumwaa,Yigang Yu,Xinglong Xiao
Staphylococcus aureus ( S. aureus ) is known to be one of the most common foodborne pathogens capable of secreting a wide range of exotoxins such as enterotoxin , which severely threatens the health of consumers. Over the past few years, the development of safe and effective strategies in inhibiting the growth and enterotoxins generation of S. aureus in food turns out to be the research focus and emphasis. This research explores citronellal (CIT), a native compound with extensive existence in spices, which could effectively inhibit the growth and enterotoxins generation of S. aureus (ATCC 29213). Results from minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill curves, showed that CIT could tremendously inhibit the growth of S. aureus . Analysis on hemolysin showed that CIT at sub-MIC could significantly (p < 0.05) inhibit the hemolytic activity of S. aureus . As revealed by the results of ELISA , the production of enterotoxins in the culture supernatant and pork meat decreased significantly (p < 0.05) after exposure to CIT at sub-MIC. Furthermore, a significant (p < 0.05) decrease in dose-dependent was found in the transcription levels of virulence-related genes. In all, CIT proved to be a possible inhibitor of the growth and enterotoxins production of S. aureus with highly promising application in the food industry.
研究领域:
食品科学
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微生物学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2022
·Vol. 23
·期 2
·2200430
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IF 5.859
Yu Zhao,Jiaying Yang,Danli Hao,Ran Xie,Lingyu Jia,Miyi Yang,Hai Ma,Pengqian Wang,Weipeng Yang,Feng Sui,Haiyu Zhao,Yanjun Chen,Qinghe Zhao
Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple inflammations. The biofilm formed by MRSA is resistant to a variety of antibiotics and is extremely difficult to cure, which seriously threatens human health. Herein, a nanoparticle encapsulating berberine with polypyrrole core and pH-sensitive shell to provide chemo-photothermal dual therapy for MRSA infection is reported. By integrating photothermal agent polypyrrole, berberine, acid-degradable crosslinker, and acid-induced charge reversal polymer, the nanoparticle exhibited highly efficient MRSA infection treatment. In normal uninfected areas and bloodstream, nanoparticles showed negatively charged, demonstrating high biocompatibility and excellent hemocompatibility. However, once arriving at the MRSA infection site, the nanoparticle can penetrate and accumulate in the biofilm within 2 h. Simultaneously, berberine can be released into biofilm rapidly. Under the combined effect of photothermal response and berberine inhibition, 88.7% of the biofilm is removed at 1000 µg mL −1 . Moreover, the nanoparticles have an excellent inhibitory effect on biofilm formation, the biofilm inhibition capacity can reach up to 90.3%. Taken together, this pH-tunable nanoparticle can be employed as a new generation treatment strategy to fight against the fast-growing MRSA infection.
研究领域:
医学
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纳米技术
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感染病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Lvyuan Fan,Zhiyu Pan,Xu Liao,Yilin Zhong,Juan Guo,Rui Pang,Xinhai Chen,Guozhu Ye,Yubin Su
Background: Methicillin-resistant Staphylococcus aureus (MRSA) has now become a major nosocomial pathogen bacteria and resistant to many antibiotics. Therefore, Development of novel approaches to combat the disease is especially important. The present study aimed to provide a novel approach involving the use of nucleotide-mediated metabolic reprogramming to tackle intractable methicillin-resistant S. aureus (MRSA) infections. Objective: This study aims to explore the bacterial effects and mechanism of uracil and gentamicin in S. aureus. Methods: Antibiotic bactericidal assays was used to determine the synergistic bactericidal effect of uracil and gentamicin. How did uracil regulate bacterial metabolism including the tricarboxylic acid (TCA) cycle by GC-MS-based metabolomics. Next, genes and activity of key enzymes in the TCA cycle, PMF, and intracellular aminoglycosides were measured. Finally, bacterial respiration, reactive oxygen species (ROS), and ATP levels were also assayed in this study. Results: In the present study, we found that uracil could synergize with aminoglycosides to kill MRSA (USA300) by 400-fold. Reprogramming metabolomics displayed uracil reprogrammed bacterial metabolism, especially enhanced the TCA cycle to elevate NADH production and proton motive force, thereby promoting the uptake of antibiotics. Furthermore, uracil increased cellular respiration and ATP production, resulting the generation of ROS. Thus, the combined activity of uracil and antibiotics induced bacterial death. Inhibition of the TCA cycle or ROS production could attenuate bactericidal efficiency. Moreover, uracil exhibited bactericidal activity in cooperation with aminoglycosides against other pathogenic bacteria. In a mouse mode of MRSA infection, the combination of gentamicin and uracil increased the survival rate of infected mice. Conclusion: Our results suggest that uracil enhances the activity of bactericidal antibiotics to kill Gram-positive bacteria by modulating bacterial metabolism.
研究领域:
微生物学
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药理学
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传染病学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2023
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IF 5.2
Zhao-xia Luo,Yuting Li,Mei-fang Liu,Rui Zhao
Staphylococcus aureus readily forms biofilms on host tissues and medical devices, enabling its persistence in chronic infections and resistance to antibiotic therapy. The accessory gene regulator (Agr) quorum sensing system plays a key role in regulating S. aureus biofilm formation. This study reveals the widely used fluoroquinolone antibiotic, ciprofloxacin, strongly stimulates biofilm formation in methicillin-resistant S. aureus , methicillin-sensitive S. aureus , and clinical isolates with diverse genetic backgrounds. Crystal violet staining indicated that ciprofloxacin induced a remarkable 12.46- to 15.19-fold increase in biofilm biomass. Confocal laser scanning microscopy revealed that ciprofloxacin induced denser biofilms. Phenotypic assays suggest that ciprofloxacin may enhance polysaccharide intercellular adhesin production, inhibit autolysis, and reduce proteolysis during the biofilm development, thus promoting initial adhesion and enhancing biofilm stability. Mechanistically, ciprofloxacin significantly alters the expression of various biofilm-related genes ( icaA , icaD , fnbA , fnbB , eap , emp ) and regulators ( agrA , saeR ). Gene knockout experiments revealed that deletion of agrC , rather than saeRS , abolishes the ciprofloxacin-induced enhancement of biofilm formation, underscoring the key role of agrC . Thermal shift assays showed ciprofloxacin binds purified AgrC protein, thereby inhibiting the Agr system. Molecular docking results further support the potential interaction between ciprofloxacin and AgrC. In summary, subinhibitory concentrations of ciprofloxacin stimulate S. aureus biofilm formation via an agrC -dependent pathway. This inductive effect may facilitate local infection establishment and bacterial persistence, ultimately leading to therapeutic failure.
研究领域:
微生物学
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分子生物学
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传染病学
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药理学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Hongmin Gao,Hehua Zhang,Xue Qi,Meng Miao,Longbin Que,Xin Gu,Dong Chang,Hongzhi Pan
Accurate and reliable detection of Staphylococcus aureus ( S. aureus ) is essential for preventing infections, particularly in healthcare and food safety contexts. This work presents a novel dual-mode biosensor that integrates the CRISPR/Cas12a system with an enzyme-free isothermal amplification method for detecting S. aureus . Hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) amplify the aptamer-triggered response, significantly enhancing sensitivity. CRISPR/Cas12a′s nuclease activity is utilized in two modes: cis cleavage generates a fluorescence signal, while trans cleavage produces an electrochemical signal, enabling dual-mode detection. The biosensor demonstrates outstanding performance, with a limit of detection (LOD) as low as 5.7 CFU mL −1 in electrochemical mode and 133.7 CFU mL −1 in fluorescence mode, showcasing excellent accuracy, stability, and sensitivity. It has been successfully applied to detecting actual samples, confirming its practical applicability. This innovative approach offers a powerful tool for the swift and precise identification of S. aureus and paves the way for developing next-generation dual-mode biosensors for various analytes. Future research will aim to simplify the detection process further, making it more accessible for use in resource-limited settings.
研究领域:
分子生物学
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病原体检测
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生物传感技术
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Qianwei Qu,Xingyu Huang,Zhenxin Zhu,Jun Wang,Mengmeng Zhao,Wenqiang Cui,Yadan Zheng,Yanyan Liu,Xueying Chen,Zhiyun Zhang,Na Dong,Chunliu Dong,Yanhua Li
Background Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti- S. aureus effect. Nevertheless, the specific mechanism of action of sanguinarine against S. aureus biofilms remains unexplored. Purpose The objective of this study was to elucidate the target site of sanguinarine in S. aureus , as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics. Methods Initially, we assessed the in vitro anti- S. aureus properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with S. aureus biofilm formation was preliminarily analyzed in vitro . Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated in vivo using mouse models of biofilm and bacteremia. Results Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering S. aureus biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the S. aureus load in mouse organs and the formation of biofilm on the surface of implants in vivo without any resistance. Conclusions In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of S. aureus and targeting IGPD. These findings suggest that sanguinarine holds potential for further development as a novel antibiotic to combat biofilm-associated infections.
研究领域:
微生物学
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药理学
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感染与免疫
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）