Antibiotics-Basel
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2025
·Vol. 14
·期 8
·799
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IF 4.6
Sijin Hang,Li Wang,Zhe Ji,Xuqing Shen,Xinyu Fang,Wanqian Li,Yuanying Jiang,Hui Lu
Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility ofC. albicansto antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility ofC. albicansto azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles againstC. albicansby inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis inC. albicans. Conclusions: InC. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles.
研究领域:
微生物学
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分子生物学
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药理学
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真菌学
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感染性疾病
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DOI
PubMed
高影响因子
MYCOLOGIA
·
2021
·
IF 2.696
Lili Wang,Min Zhang,Jian Guo,Wenzheng Guo,Ni Zhong,Hui Shen,Jinfeng Cai,Zhaoqin Zhu,Wenjuan Wu
Recently, Cryptococcus and non-albicans Candida (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant Cryptococcus and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against Cryptococcus spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC90 value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, whereas for Candida parapsilosis the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating Cryptococcus and NAC infections.
研究领域:
医学
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微生物学
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药理学
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DOI
PubMed
高影响因子
BMC GENOMICS
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2025
·Vol. 26
·期 1
·1-16
·
IF 3.7
Liu Zhen,Ma Xiaoping,Zeng Xiangwen,Li Zhiguo,Liu Ruiguo,Luo Rongyan,Wang Weichen,Tahir Muhammad Salman,Wang Chengdong,Gu Yu
Alcohol dehydrogenase has been studied in regulation of fungal growth and development, stress response and pathogenesis, but its function in T. asahii remains unexplored. In this study, we analyzed the ADH gene family in T. asahii for the first time, identifying six ADH genes and containing conserved ADH_N and ADH_Zinc_N domains. We constructed an overexpression strain of the most significantly differentially expressed gene TaADH_like and compared its phenotypes with those of the wild-type strain, focusing on colony morphology, biofilm biomass, stress response, drug resistance, and pathogenicity. The results showed that TaADH_like overexpression reduced sensitivity to hypoxic conditions, altered the hyphae-to-yeast transition, and led to slower growth, decreased colonization ability, reduced tissue damage, and lower lethality. Increased osmotic stress sensitivity and the involvement of the HOG MAPK pathway in the hyphae-to-yeast conversion contributed to the reduced colonization capacity of T. asahii . Furthermore, the overexpression of TaADH_like promoted biofilm formation and led to a slight enhancement in fluconazole resistance in T. asahii . This study is the first to elucidate the function of the alcohol dehydrogenase gene in T. asahii , providing a foundation for future genetic research on this pathogen.
研究领域:
微生物学
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遗传学
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医学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Wang Hongkang,Ji Zhe,Feng Yanru,Yan Tianhua,Cao Yongbing,Lu Hui,Jiang Yuanying
Introduction: Extrusion of azoles from the cell, mediated by an efflux pump Cdr1, is one of the most frequently used strategies for developing azole resistance in pathogenic fungi. The efflux pump Cdr1 is predominantly localized in lipid rafts within the plasma membrane, and its localization is sensitive to changes in the composition of lipid rafts. Our previous study found that the calcineurin signal pathway is important in transferring sphingolipids from the inner to the outer membrane.Methods: We investigated multiple factors that enhance the antifungal activity of fluconazole (FLC) using minimum inhibitory concentration (MIC) assays and disk diffusion assays. We studied the mechanism of action of myriocin through qRT-PCR analysis and confocal microscopy analysis. We tested whether myriocin enhanced the antifungal activity of FLC and held therapeutic potential using a mouse infection model.Results: We found that this signal pathway has no function in the activity of Cdr1. We found that inhibiting sphingolipid biosynthesis by myriocin remarkably increased the antifungal activity of FLC with a broad antifungal spectrum and held therapeutic potential. We further found that myriocin potently enhances the antifungal activity of FLC against C. albicans by blocking membrane localization of the Cdr1 rather than repressing the expression of Cdr1. In addition, we found that myriocin enhanced the antifungal activity of FLC and held therapeutic potential.Discussion: Our study demonstrated that blocking the membrane location and inactivating Cdr1 by inhibiting sphingolipids biogenesis is beneficial for enhancing the antifungal activity of azoles against azole-resistant C. albicans due to Cdr1 activation.
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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产品关联
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
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2023
·
IF 7.7
Zi-Ying Zeng,Dong-Dong Zhou,Shu-Tong Yang,Miao-Miao Su,Zhong-Hua Yang
This work synthesized a novel adsorbent by doping COF and MIL-125(Ti) in the nanoparticles Fe 3 O 4 . The obtained results showed that the doping of COF and MIL-125(Ti) had a positive effect on enhancing the specific surface area and adsorption capacity. Moreover, the adsorption process has been confirmed to follow the Langmuir model and pseudo-second-order kinetic, and the maximum adsorption capacity for tetracycline and tebuconazole was 138.1 mg/g and 87.73 mg/g, respectively. Finally, the adsorbent displayed an excellent adsorption performance in three kinds of actual environmental water samples. The mechanics of the adsorption process mainly involved π-π stacking interaction, hydrogen-bonding interaction, electrostatic interaction, and complexation interaction. In short, the synthesized magnetic adsorbent displayed a good application potential for removing tetracycline and tebuconazole from wastewater.
研究领域:
环境科学
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材料科学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2019
·
IF 8.355
Donghai Wu,Guanghua Lu,Jingjing Yao,Chao Zhou,Fuli Liu,Jianchao Liu
Copper ferrite modified carbon nanotubes (CuFe 2 O 4 /CNTs) were synthesized and employed as adsorbents/catalysts to assist electro-peroxone treatment of aqueous emerging pollutant fluconazole (FLC). Results suggest that the synthetic CuFe 2 O 4 /CNTs integrated the CNTs adsorption and ferrite magnetic abilities, showing a fast FLC removal and an excellent recyclability. The pseudo-second-order equation and the Langmuir isotherm model could well elaborate the adsorption of FLC on prepared catalysts. Compared to individual processes, electro-peroxone treatment exhibited a synergetic degradation of FLC. Approximately 89% FLC transformation was observed in the CuFe 2 O 4 /CNTs catalytic electro-peroxone process, 10% higher than that without catalysts, implying that CuFe 2 O 4 /CNTs could enhance the peroxone oxidation. Increasing of inlet gasphase ozone concentration (7.2–29.7 mg/L), catalysts dose (0.1–0.8 g/L), initial solution pH (3–11), and reaction temperature (10–30 °C) could improve the treatment efficiency, while initial FLC concentration (5–40 mg/L) and natural organic matter contents (humic acid, 0–20 mg/L) have opposite effects. The role of cathodic current density (10–60 mA/cm 2 ) was complex, 40 mA/cm 2 was observed as the optimal value. Furthermore, the degradation of FLC followed the hydroxyl radicals (HO ) oxidation mechanism. The production of HO was mainly via peroxone reactions, and the presence of CuFe 2 O 4 /CNTs could catalytic ozone and H 2 O 2 decomposition, thereby promoting HO generation. Although the magnetic CuFe 2 O 4 /CNTs had not shown obvious microelectrode characteristics, it combined adsorption and catalytic peroxone oxidation, may serve as the catalyst for electro-peroxone process.
研究领域:
环境科学
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材料科学
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化学工程
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产品关联
DOI
高影响因子
MYCOPATHOLOGIA
·
2025
·Vol. 190
·期 5
·1-14
·
IF 2.9
Ma Yinzheng,Yu Mingqi,Qian Jianing,Bao Bingzhangke,Ma Xinyi,Li Zijie,Wu Zibei,Jia Yuzhong,He Xiaowen
Systemic candidiasis caused by Candida albicans has become a serious issue due to high morbidity and mortality. It is very important to develop novel and effective antifungal agents due to the increasing resistance to commonly used drugs such as fluconazole (FLC). In our previous research, the essential oil of Carica papaya L. seed (PSEO) was extracted and in vitro studies demonstrated that PSEO exhibited strong antifungal activity against C. albicans . It is crucial to investigate the therapeutic effect of PSEO in vivo to develop it into a viable antifungal agent. This study aimed to investigate acute toxicity of PSEO and its in vivo effects on a systemic candidiasis model in mice induced with both FLC-sensitive and -resistant C. albicans . The results showed that PSEO showed no acute toxicity up to 100 mg/kg. PSEO and FLC can improve the water intake, food intake, and mental state of systemic candidiasis model mice. The body weight of the infected mice recovered, the survival rate and splenic index increased, the fungal burden decreased, and pathological damage was alleviated to varying degrees. Moreover, the higher the dose of PSEO, the more pronounced the effect. PSEO exhibited significantly better efficacy than FLC against FLC-resistant C. albicans -induced systemic candidiasis. These findings indicate that PSEO holds great promise as a natural, novel, and effective agent for clinical treatment of C. albicans infections, especially for drug-resistant C. albicans infections. This study provides a theoretical basis for the rational development and utilization of papaya seeds.
研究领域:
微生物学
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药理学
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感染性疾病
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天然药物化学
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产品关联
DOI
PubMed
高影响因子
Atmospheric and Oceanic Optics
·
2024
·Vol. 37
·期 5
·715-718
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IF 0.9
Baklanov A. M.,Protasov A. A.,Stekleneva M. E.,Valiulin S. V.
—Infectious diseases affecting the respiratory system are currently a serious medical problem. One of the ways of increasing the effectiveness of therapy for such diseases is targeted delivery of drugs. This approach requires the development of new methods for generating aerosols of drugs with particle sizes which enable penetrating into specified areas of the respiratory system. In this work, a technique for generating dry aerosol particles based on ultrasonic spraying of a drug solution is suggested and implemented. Using the example of a solution of the medicinal antifungal substance fluconazole, we show that this technique enables generating aerosol particles with stable concentration and average size for more than 2 hours. The resulting aerosol has optimal inhalation parameters: size from 1 to 1.9 microns and concentration of 70 000 ± 6500 cm −3 . The suggested technique makes it possible to further study the biological effect of aerosols of drugs.
研究领域:
药剂学
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呼吸系统疾病
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生物医学工程
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产品关联
DOI
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 12
·4308-4316
·
IF 6.843
Jie Zhang,Zhengyu Liu,Haomin Wu,Ting Cai
Amorphous solids have been widely used to improve the solubility and oral bioavailability of poorly water-soluble drugs. Biocompatible polymeric materials are usually incorporated into formulations to inhibit the crystallization of high-energy amorphous drugs. Crystallization typically consists of two steps, nucleation and crystal growth. The impacts of polymeric excipients on the crystal growth of amorphous drugs have been intensively studied. However, the nucleation behaviors of amorphous drugs in the presence of polymers remain largely unexplored. Herein, we report that three chemically distinct polymers show significantly different effects on nucleation kinetics of amorphous fluconazole (FCZ), a classical antifungal drug. The addition of 10% w/w HPMCAS shows the largest inhibitory effect on the nucleation rates of FCZ, while the same amount of PVP has only a minor effect. Conversely, the nucleation rates for both polymorphs of FCZ are significantly increased in the presence of PEO. In addition, the polymeric additives are found to influence the kinetics of nucleation and crystal growth to a similar extent, suggesting that the two processes may share a similar kinetic barrier. The present study is helpful in the optimization of formulations of amorphous solid dispersions and understanding the nucleation behavior of polymorphic drugs.
研究领域:
药剂学
·
材料科学
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DOI
PubMed
高影响因子
INFECTION GENETICS AND EVOLUTION
·
2021
·
IF 3.342
Dongmei Jia,Wenping Sun
Objectives A frequent emergence of drug resistance has been observed and posed great threat to global public health recently. This work aimed to investigate the potential synergistic effect and the underlying mechanisms of AgNPs-fluconazole combination more extensively through 2 clinically isolated fluconazole-resistant Candida albicans ( C. albicans ) strains. Methods Antifungal properties of AgNPs and fluconazole alone or together against planktonic cells and biofilms were tested. Cellular and molecular targets associated with fluconazole resistance were monitored after AgNPs treatment. Antifungal potential of AgNPs-fluconazole combination was also explored in vivo using a mouse model of disseminated candidiasis. Tissue burden and survival rate were analyzed. Results The results indicated that AgNPs worked synergistically with fluconazole against both planktonic cells of fluconazole-resistant C. albicans and biofilms formed <12 h. AgNPs treatment down-regulated ERG1 , ERG11 , ERG25 , and CDR2 , decreased membrane ergosterol levels and membrane fluidity, reduced membrane content of Cdr1p, Cdr2p, and thus efflux bump activity. The elevated ROS production was also a likely cause of the synergistic effect. In vivo , AgNPs and fluconazole combination significantly decreased the fungal burden and improved the survival rate of infected mice. Conclusion In conclusion, these results further confirm that AgNPs-fluconazole combination is a hopeful strategy for the treatment of fluconazole-resistant fungal infections.
研究领域:
微生物学
·
药理学
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感染性疾病
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产品关联
DOI
PubMed
高影响因子
ChemMedChem
·
2013
·Vol. 9
·期 1
·207-216
·
IF 2.835
Hong Liu,Liang Wang,Yan Li,Jiang Liu,Maomao An,Shaolong Zhu,Yongbing Cao,Zhihui Jiang,Mingzhu Zhao,Zhan Cai,Li Dai,Tingjunhong Ni,Wei Liu,Simin Chen,Changqing Wei,Chengxu Zang,Shujuan Tian,Jingyu Yang,Chunfu Wu,Dazhi Zhang,Hua Liu,Yuanying Jiang
Graphical Build it better: Structural optimization of berberine led to the identification of the novel scaffold of N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a – l , which exhibited remarkable in vitro synergistic antifungal activity against fluconazole-resistant Candida albicans in combination with fluconazole. Compound 7 d exhibited much lower cytotoxicity than berberine toward human umbilical vein endothelial cells. We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. A structure–activity relationship study of 95 analogues led us to identify the novel scaffold of N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a – l , which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound 7 d ( N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(2-fluorophenyl)acetamide) significantly decreased the MIC 80 values of fluconazole from 128.0 μg mL −1 to 0.5 μg mL −1 against fluconazole-resistant C. albicans and exhibited much lower levels of cytotoxicity than berberine toward human umbilical vein endothelial cells.
研究领域:
药理学
·
抗感染研究
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2017
·
IF 6.216
Ji-Feng Yang,Li-Ming Yang,Song-Bai Zhang,Li-Hui Ou,Cheng-Bin Liu,Li-Ying Zheng,Yu-Feng Yang,Guang-Guo Ying,Sheng-Lian Luo
The azole fungicide fluconazole (FLC) is persistent in conventional wastewater treatment plants, thus posing potential threats to human and ecosystem health. This study investigated the oxidation of FLC in aqueous solution by thermally activated persulfate (TAP) under different operation conditions. Higher temperature greatly improved the removal rate of FLC (0.057 h −1 for 30 °C and 0.223 h −1 for 60 °C) and the relationship between pseudo-first-order rate constant ( k obs ) and temperature fit the Arrhenius equation, with a comparatively low activation energy of 37.8 kJ mol −1 . The degradation rate constants were enhanced with the increase of PS concentration during FLC oxidation (0.072 h −1 for 1.0 mM PS and 0.50 h −1 for 20 mM PS). Solution pH influenced the k obs of FLC degradation and the highest and lowest degradation rates were obtained at pH 3 (0.51 h −1 ) and pH 5 (0.23 h −1 ), respectively. Increasing the level of natural water constituents (HCO 3 − , Cl − , and humic acid) significantly inhibited FLC degradation. Geometry optimization of FLC was performed using density functional theory (DFT) and the data indicated that the C3 atom in the benzene ring was the most reactive site. SPE-HPLC/MS/MS analysis showed that intermediate products could form during FLC oxidation by PS and the total organic carbon (TOC) results indicated that FLC could be mineralized into CO 2 and H 2 O. Accordingly, a plausible pathway for the degradation of FLC by the thermally activated PS could be proposed. The results of this study suggested that TAP is an applicable approach for the removal of azole fungicides in water.
研究领域:
环境科学
·
化学工程
✓ 已验证
DOI
高影响因子
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