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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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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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Yue Cai,Xinrui Zhang,Wentao Hu,Fuhang Song,Hong Wang,Huawei Zhang,Xuanrong Sun
Transdermal drug delivery represents a promising avenue for the treatment of dermatologic diseases, such as cutaneous melanoma and skin infections. This study involves the development of a novel therapeutic strategy that employs a skin-penetrating peptide SPACE-modified flexible liposomal chrysomycin A (CA@SPACE-LP) with a particle size of 111.5 nm. In vitro transdermal experiments demonstrated that CA@SPACE-LP was effective in enhancing the ability of the drug to penetrate the stratum corneum and enter deep into the skin tissue, increasing the intradermal drug concentration up to threefold compared to free CA. Furthermore, CA@SPACE-LP was observed to maintain the biological activity of CA against planktonic Methicillin-resistant Staphylococcus aureus (MRSA) and melanoma cells. In vivo studies demonstrated that the topical administration of CA@SPACE-LP was efficacious in controlling the progression of cutaneous melanoma, with a tumor suppression rate of approximately 60 %, which was more pronounced than that observed with intravenous Taxol. Furthermore, CA@SPACE-LP demonstrated efficacy in the management of intradermal MRSA infections, with a significantly reduced area of ulceration in the treated mice (0.25 cm 2 ) compared to the positive control drug (Mupirocin Ointment). These results suggest that the topical delivery system developed in this study has the potential to be used for the simultaneous treatment of skin cancer and invasive MRSA infection.
研究领域:
药剂学
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皮肤病学
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肿瘤学
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微生物学
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PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2026
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IF 4.1
Yi Jintao,Fu Nani,Zhong Wenhui,Liu Xia,Zhou Anqi,Li Xun
Amoxicillin (AMO), a penicillin antibiotic, and ciprofloxacin (CIP), a quinolone antibiotic, are widely used to combat bacterial infections and are frequently co-administered to enhance therapeutic efficacy. However, improper use of AMO and CIP may lead to antibiotic residues in the environment, posing serious threats to human health. The visual detection of AMO and CIP remains significant challenges. Herein, the Eu-DPA@CQDs was used for the dual-mode detection of AMO and CIP, which was synthesized by CQDs doped in europium-DPA metal-organic framework. In the colorimetric mode, the catalase-mimicking Eu-DPA@CQDs oxidized TMB to blue oxTMB. Upon addition of AMO, the oxTMB was reduced, causing color fading. Subsequent introduction of CIP restored nanozyme activity, regenerating the blue signal and enabling dual-analyte antibiotic detection. In the fluorescence mode, the Eu-DPA@CQDs probe exhibited dual emission at 440 nm and 613 nm. Upon AMO addition, the fluorescence at both wavelengths was quenched, accompanied by a color change from red to purple. In the presence of CIP, the emission at 440 nm increased and redshifted to 490 nm, while the signal at 613 nm was quenched, resulting in a multicolor transition from red to cyan. The Eu-DPA@CQDs sensor enabled rapid and dual-mode detection of AMO and CIP. The colorimetric method exhibited wide linear ranges of 0.005–25 μM for AMO and 0.007–4.25 μM for CIP, with detection limits of 1.67 nM and 3.75 nM, respectively. A visible color transition from dark blue to colorless was observed with increasing AMO concentration, while the addition of CIP reversed the signal back to dark blue. Similarly, the fluorescence detection achieved wide linear ranges from 0.005 to 30 μM for AMO and 0.005 to 15 μM for CIP, with detection limits as low as 4.74 nM and 3.11 nM, respectively, also within only 1 min. As the concentration of AMO increased, the color shifted from red to purple. In contrast, increasing CIP concentration induced a color transition from red to cyan. These color transitions were both clearly visible to the naked eye. The sensor demonstrated excellent selectivity and anti-interference capability, providing a reliable platform for accurate, sensitive, and quantitative determination of both antibiotics in real samples. Graphical abstract
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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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PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 14
·4613
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IF 4.927
Haohua Liu,Yue Cai,Yuteng Chu,Xiaojie Yu,Fuhang Song,Hong Wang,Huawei Zhang,Xuanrong Sun
Chrysomycin A, a compound derived from marine microorganisms, proved to have a specific great in vitro inhibitory effect on methicillin-resistantStaphylococcus aureus(MRSA). It exhibits high safety for the skin, as well as a better therapeutic effect than the current clinical drug, vancomycin. Nevertheless, its poor water solubility highly limits the application and reduces the bioavailability. In view of this, we developed a cream of chrysomycin A (CA) to enhance the solubility for the treatment of skin infection, while avoiding the possible toxicity caused by systemic administration. A comprehensive orthogonal evaluation system composed of appearance, spreading ability, and stability was established to find the optimal formula under experimental conditions. The final product was odorless and easy to be spread, with a lustrous, smooth surface. The particle size of the product met Chinese Pharmacopoeia specifications and the entire cream showed long-term stability in destructive tests. The in vitro and in vivo studies indicated that CA cream had a similar anti-MRSA activity to commercially available mupirocin, showing its potential as an efficacious topical delivery system for skin infections treatment.Keywords:MRSA;chrysomycin A;cream;topical administration;skin infections
研究领域:
微生物学
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药剂学
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医学
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PubMed
高影响因子
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