BIOCHEMICAL PHARMACOLOGY
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2023
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IF 5.8
Huan Zeng,Minjing Cheng,Jingyi Liu,Chunxia Hu,Shilin Lin,Ruiqin Cui,Haibo Li,Wencai Ye,Lei Wang,Wei Huang
The epidemic of methicillin-resistant Staphylococcus aureus (MRSA) infections has created a critical health threat. The drug resistance of MRSA makes the development of drugs with new modes of action particularly urgent. In this study, we found that a natural product derivative pyrimirhodomyrtone (PRM) exerted antibacterial activity against S. aureus , including MRSA, both in vitro and in vivo . Genetic and biochemical studies revealed the interaction between PRM and N -acetylglucosamine-6-phosphate deacetylase (NagA) and the inhibitory effect of PRM on its deacetylation activity. We also found that PRM causes depolarization and destroys the integrity of the cell membrane. The elucidation of the antibacterial mechanism will inspire the subsequent development of new anti-MRSA drugs based on PRM.
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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DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
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2022
·
IF 1.424
Yuhao Ma,Zahariah Hasan,Jia Huang,Jun Chen,Chun Loong Ho
As microbes that thrive in the host body primarily have adaptive abilities that facilitate their survival, methods for classifying and identifying their nature would be beneficial in facilitating their characterization. Currently, most studies focus only on one specific characterization method; however, the isolation and identification of microorganisms from the host is a continuous process and usually requires several combinatorial characterization methods. Herein, we describe methods of identifying the microbial biofilm-forming ability, the microbial respiration state, and their chemotaxis behavior. The methods are used to identify five microbes, three of which were isolated from the bone tissue of Sprague-Dawley (SD) rats (Corynebacterium stationis, Staphylococcus cohnii subsp. urealyticus, and Enterococcus faecalis) and two from the American Type Culture Collection (ATCC)-Staphylococcus aureus ATCC 25923 and Enterococcus faecalis V583. The microbes isolated from the SD rat bone tissue include the gram-positive microbes. These microbes have adapted to thrive under stressful and nutrient-limiting environments within the bone matrix. This article aims to provide the readers with the specific know-how of determining the nature and behavior of the isolated microbes within a laboratory setting.
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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DOI
PubMed
高影响因子
Contrast Media & Molecular Imaging
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2022
·
IF 3.009
Qingxiang Li,Ke Xing Huang,Sheng Pan,Chun Su,Juan Bi,Xuan Lu
Staphylococcus aureus (S. aureus) is a typical kind of symbiotic bacteria, which can cause human pneumonia, food poisoning, and other health problems. Nowadays, the corresponding prevention and treatment have been a hot issue of general concern in related research areas. However, the mechanism of action against S. aureus is not well understood. In order to tackle such problem, we used broth microdilution to discuss the antibacterial effect of 5-methyl-2-isopropylphenol and determine inhibitory concentration. In addition, membrane potential and lipid peroxidation levels were also measured under experimental conditions. The experimental results suggested that 300 μg/mL thymol might cause cell membrane damage and decrease of NADPH concentration and increase of NADP+ and lipid peroxidation level. In such condition, thymol has the potential to result in membrane rupture and disruption of cellular homeostasis. Furthermore, we also found that NOX2 is involved in maintaining the balance of NADPH/NADP+ in cells. Finally, our work confirms that NOX2 is a potential downstream target for thymol in the cell. Such target can provide specific guidance and recommendations for its application in antifungal activity. Meanwhile, our study also provides a new inspiration for the molecular mechanism of thymol’s bacteriostatic action.
研究领域:
微生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2020
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IF 4.236
Zhou Linying,She Pengfei,Tan Fang,Li Shijia,Zeng Xianghai,Chen Lihua,Luo Zhen,Wu Yong
Recently, the problem of bacterial resistance has been brought into focus, which makes the development of new antibiotics become a necessity. Compared with traditional development approaches, drug repurposing provides a faster and more effective approach to find new antimicrobial agents. In this study, we found that antispasmodic agent otilonium bromide had strong antibacterial ability and bactericidal activity against Staphylococcus aureus, with minimal inhibitory concentrations (MICs) of 4–8 μg/ml, and bacteria could be killed completely after treatment with 2× MIC of otilonium bromide for 5 h. Furthermore, it had a potent effect on eradicating biofilm at concentrations ranging from 16 to 64 μg/ml. At the same time, it had low tendency to develop resistance and possessed limited cytotoxicity. In the methicillin-resistant S. aureus–infected mouse peritonitis model, it was also effective to cure mice and improve their survival rate. In addition, we observed that otilonium bromide changed the permeability of bacterial membrane and caused membrane damage, and it is probably the antibacterial mechanism of otilonium bromide. Taken together, our results indicated that otilonium bromide could be a new antimicrobial agent to treat S. aureus infections more safely and efficiently.
研究领域:
药理学
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微生物学
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传染病学
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DOI
PubMed
高影响因子
BIOPHYSICAL CHEMISTRY
·
2026
·
IF 2.3
Sijie Wu,Xiaomin Ren,Ronger Wu,Jia Cheng,Xiaoyong Huang
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) calls for novel antibiotic adjuvants. Carvacrol (Car), a natural monoterpene phenol derived from the essential oils of aromatic plants, exhibits membrane-active properties and has potential as an antibacterial adjuvant. Here, we found that Car markedly enhanced the bactericidal activities of Gentamicin (Gen) against MRSA. Mechanistically, Car dissipated membrane potential, inhibited respiratory chain dehydrogenase activity, and depleted intracellular ATP. Moreover, Car promoted membrane lipid peroxidation, ultimately leading to structural and functional membrane damage and bacterial death. Notably, pharmacological perturbation of respiratory and metabolic pathways further supported that this synergistic effect depends on bacterial respiratory bioenergetics. In addition, the combination showed favorable in vivo antibacterial efficacy in both Galleria mellonella and murine infection models, without apparent toxicity under the tested conditions. Collectively, these findings indicate that Car may serve as a natural antibacterial adjuvant for combination therapy against drug-resistant infections.
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高影响因子
Virulence
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2026
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IF 6.8
Xueting Wan,Yuan Wu,Qi Yang,Ruolan Wu,Ti Chen,Zhen Luo
The synergistic interaction between Staphylococcus aureus and Candida albicans exacerbates polymicrobial infection severity and mortality compared to monomicrobial infections. C. albicans metabolism is known to enhance S. aureus virulence, whereas the role of S. aureus metabolic reprogramming in this cross-species synergy remains poorly defined. In this study, we demonstrate that C. albicans remodels S. aureus glycolytic pathways, thereby increasing its virulence in glucose-rich environments. C. albicans triggers metabolic reprogramming in S. aureus, characterized by a reduction of lactate and accumulation of upstream glycolytic intermediates, including 3-phosphoglycerate, 2-phospho-D-glycerate, and phosphoenolpyruvate. The metabolic reprogramming phenotype is glycolysis-dependent, which is evidenced by 2-deoxy-D-glucose-mediated inhibition of virulence enhancement. Addition of exogenous lactate lowers extracellular pH and reduces the hemolytic activity of S. aureus-C. albicans co-cultures. Inhibition of lactate dehydrogenase by oxamate or extracellular alkalinization with sodium hydroxide significantly increases hemolysis in S. aureus mono-cultures. S. aureus-C. albicans co-infections promote inflammatory cell infiltration but do not affect the quantity of S. aureus, indicating that increased toxin levels, rather than bacterial quantity, drive the enhanced virulence. Collectively, these findings indicate that C. albicans enhances S. aureus virulence through metabolic reprogramming. Targeting lactate metabolism or glycolytic intermediates may disrupt this cooperative interaction, offering a novel therapeutic strategy against these polymicrobial infections.
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DOI
高影响因子
ELECTROCHIMICA ACTA
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2020
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IF 6.215
Zhong Wang,Hongfu Gao,Jiwen Cui,Shi Zhou,Yanli Zhao,Cai Ye,Jinlian Li,Dongmei Wu
Establishment of new method for evaluation microbial viability has become an urgent need in the fields of biology, medicine, environment and so on. In this paper, two electrochemical signals of Staphylococcus aureus ( S. aureus ) at + 0.693 and + 0.973 V vs. Ag/AgCl ( sat . KCl) were detected on the multi-walled carbon nanotube modified glassy carbon electrode (MWCNTs/GCE), and attributed to the oxidation of guanine and adenine secreted by S. aureus . For the first time, bacterial viability was evaluated from the perspective of proliferation and purine metabolism. Compared with the plate counting method, the electrochemical signals of guanine and adenine showed an earlier change of viability when S. aureus entered stationary from logarithmic phase and apoptotic from stationary phase during the growth process of S. aureus . There were good linear relationships between electrochemical signals of guanine and adenine and the number of S. aureus cells in different growth phases, but there were different detection thresholds. At the logarithmic phase, S. aureu s had stronger viability and ability to metabolize purines, which resulted in a lower detection threshold. Both electrochemical signals of bacteria could well reflect the inhibition of levofloxacin on S. aureus viability, and the guanine signal peak was closer to the result of plate counting method.
研究领域:
微生物学
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电化学
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医学检测
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DOI
高影响因子
Food Bioscience
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2020
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IF 3.067
Hong Yan,Yingying Lu,Xin Li,Yanglei Yi,Xin Wang,Yuanyuan Shan,Bianfang Liu,Yuan Zhou,Xin Lü
Bacteriocins have potential in the food industry, especially in protecting food safety and controlling food-borne diseases. Class II bacteriocin genes were previously identified from the genome of Lactobacillus crustorum MN047 and successfully expressed in Escherichia coli BL21 (DE3) using the pET-30a system. In this study, the antibacterial mechanism and potential use as a food preservative were studied. The results showed that bacteriocin BM1829 had antimicrobial activity against Gram-positive and Gram-negative bacteria with MIC values of 1–16 mg/L. In addition, BM1829 showed good stabilities to chemicals, and to thermal and pH changes. BM1829 destroyed the integrity of membranes and led to the leakage of cytoplasmic content. Flow cytometry showed that BM1829 arrested the cell cycle at R-phase. Moreover, the number of E. coli and Staphylococcus aureus cells was reduced during beef storage with BM1829 treatment. These data suggested that BM1829 has the potential to be developed as a food preservative or antibacterial agent.
研究领域:
食品科学
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微生物学
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生物技术
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DOI
高影响因子
Microbiology Spectrum
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2023
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IF 3.7
Chun-Yan Le,Yu-Jian Ye,Jian Xu,Lei Li,Xi-Qing Feng,Ni-Pi Chen,Bing-Qi Zhu,Zhi-Shan Ding,Chao-Dong Qian
The increasing prevalence of antibiotic resistance causes an urgent need for alternative agents to combat drug-resistant bacterial pathogens. Plant-derived compounds are promising candidates for the treatment of infections caused by antibiotic-resistant bacteria. Hinokitiol (β-thujaplicin), a natural tropolone derivative found in the heartwood of cupressaceous plants, has been widely used in oral and skin care products as an antimicrobial agent. The aim of this work was to study the synergy potential of hinokitiol with antibiotics against Staphylococcus aureus, which is an extremely successful opportunistic pathogen capable of causing nosocomial and community-acquired infections worldwide. The MIC was determined by the broth microdilution method, and the effect of combinations was evaluated through fractional inhibitory concentration indices (FICI). The mechanism behind this synergy was also investigated by using fluorescence spectroscopy and high-performance liquid chromatography (HPLC). The MICs of hinokitiol alone against most S. aureus strains were 32 μg/mL. Selectively synergistic activities (FICIs of ≤0.5) were observed for combinations of this phytochemical with tetracyclines against all tested strains of S. aureus. Importantly, hinokitiol at 1 μg/mL completely or partially reversed tetracycline resistance in staphylococcal isolates. The increased accumulation of tetracycline inside S. aureus in the presence of hinokitiol was observed. In addition, hinokitiol promoted the uptake of ethidium bromide (EB) in bacterial cells without membrane depolarization, suggesting that it may be an efflux pump inhibitor.IMPORTANCE The disease caused by S. aureus is a public health issue due to the continuing emergence of drug-resistant strains, particularly methicillin-resistant S. aureus (MRSA). Tetracyclines, one of the old classes of antimicrobials, have been used for the treatment of infections caused by S. aureus. However, the increased resistance to tetracyclines together with their toxicity have limited their use in the clinic. Here, we demonstrated that the combination of hinokitiol and tetracyclines displayed synergistic antibacterial activity against S. aureus, including tetracycline-resistant strains and MRSA, offering a potential alternative approach for the treatment of infections caused by this bacterium.
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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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2021
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IF 4.098
Qin Ouyang,Yongcun Yang,Shujat Ali,Li Wang,Huanhuan Li,Quansheng Chen
Staphylococcus aureus ( S. aureus ) is a pathogenic bacterium that seriously endangers food safety. Herein, a rapid, sensitive and specific aptasensor based on upconversion fluorescence resonance energy transfer (FRET) was developed for S. aureus detection in food. Aptamer-functionalized gold nanoparticles (AuNPs-aptamers) were bonded to cDNA-modified upconversion nanoparticles (UCNPs-cDNA) by complementary pairing, resulting in fluorescence quenching. After adding S. aureus into the system, the aptamers preferentially combined with S. aureus , dissociated UCNPs-cDNA from AuNPs-aptamers, and the fluorescence was recovered. Under optimized conditions, there was a significant linear correlation between fluorescence intensity and S. aureus concentration over the range 47–4.7 × 10 7 CFU/mL (R 2 = 0.9904) with a detection limit of 10.7 CFU/mL. Furthermore, the precision and accuracy of the developed biosensor were validated using standard plate count method, yielding no significant differences. The proposed method has potential application for rapid and sensitive quantification of S. aureus in food.
研究领域:
分析化学
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食品科学
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生物传感
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产品关联
DOI
PubMed
高影响因子
Microorganisms
·
2023
·Vol. 11
·期 8
·2098
·
IF 4.5
Ruining Li,Zhiwei Li,Chenxi Huang,Yifeng Ding,Jia Wang,Xiaohong Wang
Staphylococcus aureus(S. aureus) is a major foodborne pathogen. Rapid and specific detection is crucial for controlling staphylococcal food poisoning. This study reported aStaphylococcusphage named LSA2302 showing great potential for applications in the rapid detection ofS. aureus. Its biological characteristics were identified, including growth properties and stability under different pH and temperature conditions. The genomic analysis revealed that the phage has no genes associated with pathogenicity or drug resistance. Then, the phage-functionalized magnetic beads (pMB), serving as a biological recognition element, were integrated with ATP bioluminescence assays to establish a biosensing method forS. aureusdetection. The pMB enrichment brought high specificity and a tenfold increase in analytical sensitivity during detection. The whole detection process could be completed within 30 min, with a broad linear range of 1 × 104to 1 × 108CFU/mL and a limit of detection (LOD) of 2.43 × 103CFU/mL. After a 2 h pre-cultivation, this method is capable of detecting bacteria as low as 1 CFU/mL. The recoveries ofS. aureusin spiked skim milk and chicken samples were 81.07% to 99.17% and 86.98% to 104.62%, respectively. Our results indicated that phage-based biosensing can contribute to the detection of target pathogens in foods.Keywords:Staphylococcus aureus;Staphylococcusphage;magnetic beads;ATP bioluminescence assay
研究领域:
微生物学
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食品科学
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生物传感
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 1
·e0297493
·
IF 2.9
Songtao Bie,Qiuyue Mo,Chen Shi,Hui Yuan,Chunshuang Li,Tong Wu,Wenlong Li,Heshui Yu
Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S . aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC 50 ) and minimum inhibitory concentration (MIC) values against S . aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S . aureus , and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.
研究领域:
药理学
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微生物学
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抗菌研究
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产品关联
DOI
PubMed
高影响因子
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