SEPARATION AND PURIFICATION TECHNOLOGY
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2020
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IF 5.774
Qi Zhang,Siru Ren,Song Xue
In this short communication, we report the use of a steroid antibiotic, Fusidic Acid (Fus), as a novel chiral selector for enantioseparation in capillary electrophoresis (CE). Fus can be classified into the antibiotic chiral selector family but does not belong to any of the previously reported subfamilies. Factors influencing Fus in CE enantioseparations were systematically investigated including the composition of the background electrolyte (BGE), buffer pH, type and proportion of organic modifier, concentration of Fus, etc. The best separations were obtained with 50 mM phosphate buffer (pH 8.0) containing 60–70 mM Fus and 50% methanol. A preliminary analysis on the separation mechanism showed that Fus is especially suitable for the chiral analytes containing a rigid planar structure. The development of Fus as a novel chiral selector can be considered as a valuable work not only because of its unique enantioselectivity, but also because there are a number of steroids in nature that are structurally similar to Fus. This work indicates that the screening of high-efficient chiral selectors from these steroids is an attractive and promising research area.
研究领域:
分析化学
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药学
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DOI
高影响因子
Journal of Pharmaceutical Innovation
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2026
·Vol. 21
·期 1
·101
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IF 2.7
Boudoukhani Meriem,Yahoum Madiha Melha,Toumi Selma,Lefnaoui Sonia,Bañobre-López Manuel,Moulai-Mostefa Nadji
A cationic derivative of xanthan gum (Ca-XG) was synthesized through grafting of quaternary amine groups, with a degree of substitution of 0.43 confirmed by ¹H-NMR analysis. The modified polymer displayed amphiphilic behavior, characterized by a critical aggregation concentration of 0.25% (w/v), and demonstrated efficient emulsifying properties. Ca-XG was incorporated into fusidic acid emulgels, where sixteen formulations were evaluated for their physicochemical and functional characteristics. All samples showed homogeneous appearance, with pH values ranging between 5.95± 0.297 to 6.83 ± 0.352, consistent with dermal compatibility. The formulations exhibited good spreadability (32.17–66.91 cm²) and stable drug content (1.96–1.99%). Among them, the optimized formulation provided sustained permeation of fusidic acid over 24 h, with a cumulative permeation of 16.67 mg/cm² and a steady-state flux of 0.724 mg/cm².h. Furthermore, diffusion coefficients (0.015–0.051 cm²/h) confirmed the ability of Ca-XG to control drug transport while ensuring hydration of the topical matrix. Overall, these results demonstrate that Ca-XG acts not only as a bio-based emulsifier but also as a multifunctional excipient, supporting controlled drug. Graphical
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DOI
高影响因子
Infectious Microbes & Diseases
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2019
·Vol. 1
·期 2
·70
·
IF 0
Yang Fan,van der Veen Stijn
The currently recommended gonococcal therapies are rapidly losing efficacy and; therefore, novel options for treatment are urgently required to ensure future treatment remains available. Here we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic acid. These isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin, antimicrobials that are currently recommended as a first-line dual therapy. Although official susceptibility breakpoints have not been established, all gonococcal isolates appeared to be susceptible to fusidic acid, with the majority of isolates displaying a minimal inhibitory concentration (MIC) of 0.25 or 0.5 mg/L. Overall, the MIC 90 was 0.5 mg/L, with a MIC range of 0.08–2 mg/L. Importantly, no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was observed. Further analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations (4× MIC). In conclusion, fusidic acid displayed consistent antimicrobial activity against N. gonorrhoeae and, given the absence of cross-resistance with ceftriaxone and azithromycin, might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.
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DOI
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xueer Zhou,Meng Wang,Yue Wang,Jianhong Liu,Chaoliang Zhang,Jian Pan,Qiang Peng
Reversing the bacterial resistance is of great significance and importance. Fusidic acid (FA) is commonly effective against Gram-positive bacterial infections, but most Gram-negative bacteria have intrinsic resistance to FA, primarily due to the strong cell membrane-FA interactions, which highly inhibit the intracellular transport of FA. Herein, we use albumin (bovine serum albumin, BSA) as a bifunctional carrier to solubilize FA and facilitate its transmembrane delivery into Gram-negative bacterial cells. The water solubility of FA is significantly enhanced from 11.87 to 442.20 μg/mL by 5 mg/mL BSA after forming FA-BSA complex. Furthermore, FA-BSA (200 μg/mL) causes 99.96 % viability loss to the model pathogen E. coli upon incubation for 3 h, while free FA or BSA alone shows little activity. Elongation of E. coli cells after treated by FA-BSA is demonstrated by SEM, and the transmembrane transport of FA-BSA is demonstrated by CLSM. Interestingly, increasing the BSA amount substantially reduce the antibacterial activity of FA-BSA, implying an albumin-based transmembrane delivery mechanism may exist. This is the first report regarding successfully reversing the intrinsic resistance of Gram-negative bacteria to FA in the form of FA-BSA. The ready availability of albumin and the simple preparation allows FA-BSA to have great potentials for clinical use.
研究领域:
微生物学
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药学
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生物技术
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DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Xiaxia Fan,Dan Guo,Songtao Li,Jinmiao Tian,Chaotong Zhang,Zhuoyu Li
ABC transporter protein-mediated drug efflux is a significant contributor to induced resistance in breast cancer (BC). Novel therapies are therefore urgently needed to thwart chemoresistance. Herein, it is demonstrated that fusidic acid (FA) reduces the expression of ABC transporter proteins MRP1, P-gp, and BCRP, promotes the in vivo accumulation of agents, and exertes chemosensitizing effects. Further, DDX6 is identified as a direct target of FA by DARTS and biotin pull-down. Mechanistically, the results indicates that FA directly binds to H378 of DDX6, promotes its degradation, and downregulates its downstream p-GSK-3β, which in turn enhances the phosphorylation and ubiquitin-dependent hydrolysis of β-catenin S33/37/45/T41, blocks pro-resistance β-catenin signaling, and further prevents chemoresistance. The inhibitory effect of FA on chemoresistance is blocked following the knockout of DDX6 using CRISPR/Cas9. More importantly, FA also enhances the interaction between DDX6 and HSC70, while it facilitates DDX6 degradation via chaperone-mediated autophagy (CMA), thereby impairing the GSK-3β/β-catenin axis to enhance the efficacy of FA. Consistently, the effect of FA in combating chemoresistance by targeting DDX6 is evident in a xenograft mouse model. These findings reveal a direct protein target and molecular mechanism for FA to reverse chemoresistance, thus supporting the further development of FA as a chemosensitizing agent. Graphical FA directly binds to residue H378 of DDX6 and promotes its interaction with HSC70, leading to CMA degradation of DDX6, thereby impairing GSK-3β/β-catenin signaling, inhibiting ABC transporter proteins, and enhancing chemosensitivity.
研究领域:
癌症生物学
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药理学
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分子生物学
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生物化学
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细胞信号传导
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药物耐受
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自噬
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DOI
PubMed
高影响因子
Bioengineering-Basel
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2024
·Vol. 11
·期 2
·177
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IF 3.8
Jianhong Liu,Xuyang Lai,Yuanhong Li,Zhuohang Yu,Xuan Wang,Chaoliang Zhang,Qiang Peng
Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA–phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA–phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss ofE. coliand 99.1% loss ofP. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use.Keywords:drug delivery;drug resistant;phospholipid complex;antimicrobial;antibiotics
研究领域:
药学
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微生物学
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药物递送系统
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抗菌研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
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2021
·Vol. 130
·期 2
·405-415
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IF 3.772
Huang W.W.,Ge X.Y.,Huang Y.,Chai X.T.,Zhang L.,Zhang Y.X.,Deng L.N.,Liu C.Q.,Xu H.,Gao J.
AimsTo obtain the high‐yield strain of fusidic acid, which is produced from fungus Fusidium coccineum and is the only fusidane‐type antibiotic that has been used clinically, and confirm the changes in the transcription levels involved in increasing its production.Methods and ResultsBy using the atmospheric and room temperature plasma mutagenesis technology, a high‐yield mutant strain of fusidic acid‐producing fungus F. coccineum was obtained. Using the genomic analysis of the original strain based on biosynthetic pathways of ergosterol and helvolic acid, we demonstrate that the pathway involved in the biosynthesis of 2,3‐oxidosqualene from acetyl coenzyme A was shared by fusidic acid and ergosterol, and fusidic acid was finally synthesized by the catalysis of multiple cytochrome P450s and short‐chain dehydrogenase/reductase from 2,3‐oxidosqualene. Then, through the transcriptomic analysis of the original and mutagenized strain, it revealed that the proposed pathway from sucrose to fusidic acid was the most significantly up‐regulated in the transcription levels of the mutant strain.ConclusionsThe changes in the transcription levels of fusidic acid during its biosynthesis might result in high‐yield of fusidic acid in the mutant strain. This is the first report on the whole biosynthetic pathway of fusidic acid in F. coccineum.Significance and Impact of the StudyThis study obtain the genetic basis for the biosynthesis of fusidic acid which could be beneficial for the molecular modifications of F. coccineum to further increase its yield by fermentation in future, and established the foundation to reveal the mechanism of the high‐yield of the mutant strain.
研究领域:
微生物学
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基因组学
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生物技术
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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