Journal of Fungi
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2026
·Vol. 12
·期 5
·354
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IF 4.3
Yutao Zhou,Jiahao Xu,Chang Su,Weina Wu,Fengping Yi
Candida albicansis a common opportunistic pathogen. Long-term use of azole antifungals faces challenges like resistance, necessitating novel agents. Tea tree oil (TTO), a natural broad-spectrum antimicrobial, shows promise, but its molecular mechanisms, particularly concerning novel cell death pathways, require clarification. This study comprehensively evaluated the antifungal mechanism of TTO againstC. albicansusing transcriptomics. Antifungal susceptibility assays were conducted to assess the effects of TTO and its components (4-terpineol, terpenes, and γ-pinene) on the growth ofC. albicanshyphae and biofilms. Fluorescent labeling and biochemical analysis were employed to detect ferroptosis markers. Transcriptomic results indicate that TTO induces 423 differentially expressed genes and systematically inhibits the development ofC. albicanshyphae through mechanisms such as oxidative stress, iron homeostasis disruption, disruption of cell wall integrity, and interference with ergosterol metabolism. Notably, the significant enrichment of redox enzyme activity and iron ion binding functions, along with changes in the glutathione metabolic pathway, suggest that ferroptosis may be involved in this process. Subsequent studies revealed that the compound 4-pinene most effectively inhibits the pathogenicity ofC. albicansby suppressing its adhesion, hyphae formation, and biofilm formation, whereas terpinene induces the accumulation of reactive oxygen species (ROS) and increases lipid peroxidation inC. albicans; furthermore, following treatment with an iron-mediated apoptosis inhibitor, terpinene enhances the viability of the treatedC. albicanscells.
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ENVIRONMENTAL POLLUTION
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2017
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IF 5.099
Dong Zhu,Qing-Fang Bi,Qian Xiang,Qing-Lin Chen,Peter Christie,Xin Ke,Long-Hua Wu,Yong-Guan Zhu
Although the roles of earthworms and soil collembolans in the transport of microplastics have been studied previously, the effects of the soil biota at different trophic levels and interspecific relationships remain poorly understood. Here, we examine three soil microarthropod species to explore their effects on the transport of microplastics. The selected Folsomia candida and Hypoaspis aculeifer are extensively used model organisms, and Damaeus exspinosus is a common and abundant indigenous species in China. A model food chain (prey-collembolan and predator-mite) was structured to test the role of the predator-prey relationship in the transport of microplastics. Commercial Polyvinyl chloride (PVC) particles (Diameter: 80–250 μm) were selected as the test microplastics, because large amounts of PVC have persisted and accumulated in the environment. Synchronized soil microarthropods were held in plates for seven days to determine the movement of microplastics. The 5000 microplastic particles were carefully placed in the center of each plate prior to the introduction of the animals. Our results clearly show that all three microarthropod species moved and dispersed the microplastics in the plates. The 0.54%, 1.8% and 4.6% of the added microplastic particles were moved by collembolan, predatory mite and oribatid mite, respectively. Soil microarthropods (<0.2 cm) transported microplastic particles up to 9 cm. The avoidance behavior was observed in the collembolans in respect of the microplastics. The predatory -prey relationship did promote the transport of microplastics in the plates, increasing transport by 40% compared with the effects of adding single species (P < .05). Soil microarthropods commonly occur in surface soils (0–5 cm) and, due to their small body size, they can enter soil pores. Our results therefore suggest that the movement of microplastics by soil microarthropods may influence the exposure of other soil biota to microplastics and change the physical properties of soils.
研究领域:
生态学
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环境科学
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SOLID STATE SCIENCES
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2014
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IF 1.679
Lijun Dong,Chunling Ge,Peiyong Qin,Yan Chen,Qinghong Xu
In this study, MgAl-LDHs (layered double hydroxides) intercalated with sodium dodecyl sulfate and outside surface modified with (3-aminopropyl)triethoxysilane (KH550) were prepared. The existence of organic part in LDHs improved immobilization efficiency and activity recovery of candida lipolytic lipase loaded. Also the positive charge in framework of LDHs was found to be beneficial to the enzyme immobilization. An immobilization efficiency of 56.4% and an activity recovery over 69.2% of the enzyme were obtained after it was loaded on the intercalated and modified LDHs, and catalytic activity of the immobilization can be kept at least five times. Moreover, the immobilized enzyme was found to have higher temperature resistance, wider pH value and better thermostability in reactive activity.
研究领域:
生物化学
·
酶工程
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FOOD CHEMISTRY
·
2023
·
IF 8.8
Lili Yin,Kunpeng Gao,Xiangzhao Mao,Yang Hu
Lipase B from Candida antarctica (CALB) plays a prominent role as a biocatalyst in several industries, especially for biphasic conversion of functional lipids. Herein, an amphiphilic Janus halloysite nanosheet (JHNS) was fabricated and employed simultaneously as a solid surfactant for stabilizing Pickering emulsion and as a carrier for immobilizing CALB, with the aim to realize highly efficient biphasic bioconversion. The obtained JHNS could stabilize Pickering emulsion for at least 7 days. Immobilization of CALB on JHNS improved the substrate affinity, catalytic efficiency, thermal stability, and alkaline tolerance of the enzyme. Moreover, JHNS-based immobilized CALB was exploited as a biocatalytic platform for the conversion of retinyl acetate, with almost twice increase in conversion efficiency. Taken together, the JHNS-based immobilized CALB paves the way for the design of efficient biphasic conversion system for the production of added-value lipids.
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CHINESE JOURNAL OF CHEMICAL ENGINEERING
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2023
·
IF 3.8
Xiaoyun Hou,Qinghong Shi
We described a novel polymer-lipase conjugate for high-efficient esterification of vitamin E using vitamin E and succinic anhydride as the substrates in nonaqueous media. In this work, the monomer, N -isopropylacrylamide (NIPAM), was grafted onto Candida rugosa lipase (CRL) to synthesize poly(NIPAM) ( p NIPAM)-CRL conjugate by atom transfer radical polymerization via the initiator coupled on the surface of CRL. The result showed that the catalytic efficiencies of p NIPAM-CRL conjugates (19.5 – 30.3 L·s -1 ·mmol -1 ) were at least 7-times higher than that of free CRL (2.36 L·s -1 ·mmol -1 ) in DMSO. It was attributed to a significant increase in K cat of the conjugates in nonaqueous media. The synthesis catalyzed by p NIPAM-CRL conjugates was influenced by the length and density of the grafted polymer, water content, solvent polarity and molar ratio of the substrates. In the optimal synthesis, the reaction time was shortened at least 7-times, and yields of vitamin E succinate by p NIPAM- g -CRL and free CRL were obtained to be 75.4% and 10.1 % at 55°C after the reaction for 1.5 h. The result argued that conjugation with p NIPAM induced conformational change of the lid on CRL based on hydrophobic interaction, thus providing a higher possibility of catalysis-favorable conformation on CRL in nonaqueous media. Moreover, p NIPAM conjugation improved the thermal stability of CRL greatly, and the stability improved further with an increase of chain length of p NIPAM. At the optimal reaction conditions (55°C and 1.5 h), p NIPAM- g -CRL also exhibited good reusability in the enzymatic synthesis of vitamin E succinate and kept ∼ 70% of its catalytic activity after ten consecutive cycles. The research demonstrated that p NIPAM- g -CRL was a more competitive biocatalyst in the enzymatic synthesis of vitamin E succinate and exhibited good application potential under harsh industrial conditions.
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Biomaterials Science
·
2022
·Vol. 11
·期 1
·307-321
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IF 7.59
Wei Liu,Mengshun Li,Baocheng Tian,Xuesong Yang,Wei Du,Xiuwen Wang,Huihui Zhou,Chen Ding,Sixiang Sai
Fungal infections gradually lead to a high mortality rate due to difficulties in diagnosis, the limited number of antifungal drugs available, and the appearance of resistant isolates. Here, we developed a calcofluor white-cholesteryl hydrogen succinate conjugate (CFW–CHSc) as a novel nanomaterial that specifically binds to chitin chains in the cell wall. We showed that fluorescent-dye loaded CFW–CHSc-liposomes entered the cytoplasm of Candida albicans cells with increased efficacy. Voriconazole-loaded CFW–CHSc-liposomes displayed an increased antifungal activity against C. albicans yeast cells in an in vitro assay. Animal infection models and animal imaging analysis showed that fluorescent-dye loaded CFW–CHSc-liposomes maintained prolonged residence in rodent tissues. In mouse liver and kidney tissue, voriconazole-loaded CFW–CHSc-liposomes showed significantly enhanced antifungal activity when administered intravenously. Taken together, our studies confirm that CFW–CHSc increases the drug delivery efficacy of nanoparticles in vitro by interacting with chitin chains in the C. albicans cell wall. The fungi-targeting nanoparticles improve the drug delivery efficacy in vivo by enriching the nanoparticles at the site of fungal infection via the blood circulation system. Fungi-targeting nanomaterials have a promising future in the treatment of nosomycosis.
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Acta Biomaterialia
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2022
·
IF 10.633
Guowei Li,Kai Lv,Xiangjun Pan,Siting Zhou,Hui Xing,Jun Xu,Dong Ma,Yunfeng Hu,Hao Xu
The low permeability of antifungal agents to fungal biofilms , which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine , herein, a dynamic delivery system [email protected] /NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles , in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction , while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system [email protected] /NONOate could efficiently and synergistically eliminate planktonic Candida albicans ( C. albicans ) in a safe and no toxic side effect manner, and effectively cured C. albicans -induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans -induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. Statement of significance A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans , but did not show significant cytotoxicity to normal somatic cells .
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BIOPROCESS AND BIOSYSTEMS ENGINEERING
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2022
·Vol. 45
·期 4
·749-759
·
IF 3.434
Zhang Xiao-guang,Xue Yu,Lu Ze-ping,Xu Hua-jin,Hu Yi
In this study, a series of proline ionic liquids with different lengths of hydrophobic alkyl on the side chain were used to modify the Candida Antarctic lipase B (CALB). The catalytic activity, thermal stability and tolerance to methanol and DMSO of the modified enzyme were all improved simultaneously. The optimum temperature changed from 55 to 60 ℃. The hydrophobicity and anion type of the modifier have important influence on the catalytic performance of CALB. CALB modified by [ProC 12 ][H 2 PO 4 ] has a better effect. Under the optimal conditions, its hydrolysis activity was 3.0 times than that of the native enzyme, the catalytic efficiency Kcat/Km improved 2.8 times in aqueous phase, and the tolerance to organic solvent with strong polarity (50% methanol 2 h) was increased by 6.8 times. Fluorescence spectra and circular dichroism (CD) spectroscopy showed that the introduction of ionic liquids changed the microenvironment near the fluorophores of the enzyme protein, the α-helix decreased and β-sheet increased in the secondary structure of the modified enzymes. The root mean square deviation (RMSD), residue root mean square fluctuation (RMSF), radius of gyration (Rg), and solution accessible surface area (SASA) of [ProC 2 ][Br]-CALB, [ProC 12 ][Br]-CALB and native CALB were obtained for comparison by molecular dynamics simulation. The results of dynamics simulation were in good agreement with enzymology experiment. The introduction of ionic liquids can keep CALB in a better active conformation, and proline ionic liquids with long hydrophobic chains can significantly improve the surface hydrophobicity and overall rigidity of CALB. This research offers a new idea for rapid screening of efficient modifiers and provision of enzymes with high stability and activity for industrial application.
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Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xue Yu,Zhang Xiao-Guang,Lu Ze-Ping,Xu Chao,Xu Hua-Jin,Hu Yi
Various betaine ionic liquids composed of different chain lengths and different anions were designed and synthesized to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity of all modified lipases improved under different temperature and pH conditions, while also exhibiting enhanced thermostability and tolerance to organic solvents. With an increase in ionic liquid chain length, the modification effect was greater. Overall, CALB modified by [BetaineC16][H2PO4] performed best, with the modified CALB enzyme activity increased 3-fold, thermal stability increased 1.5-fold when stored at 70°C for 30 min, with tolerance increased 2.9-fold in 50% DMSO and 2.3-fold in 30% mercaptoethanol. Fluorescence and circular dichroism (CD) spectroscopic analysis showed that the introduction of an ionic liquid caused changes in the microenvironment surrounding some fluorescent groups and the secondary structure of the CALB enzyme protein. In order to establish the enzyme activity and stability change mechanisms of the modified CALB, the structures of CALB modified with [BetaineC4][Cl] and [BetaineC16][Cl] were constructed, while the reaction mechanisms were studied by molecular dynamics simulations. Results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating that modified CALB has a more stable structure. Root mean square fluctuation (RMSF) calculations showed that the rigidity of modified CALB was enhanced. Solvent accessibility area (SASA) calculations exhibited that both the hydrophilicity and hydrophobicity of the modified enzyme-proteins were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites also increased. Therefore, modified CALB has enhanced structural stability and higher hydrolytic activity.
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Cell Chemical Biology
·
2023
·
IF 8.6
Xueyang Jin,Xuben Hou,Xue Wang,Ming Zhang,Jinyao Chen,Minghui Song,Jiaozhen Zhang,Hongbo Zheng,Wenqiang Chang,Hongxiang Lou
Summary Filamentation is an important virulence factor of the pathogenic fungus Candida albicans . The abolition of Candida albicans hyphal formation by disrupting sterol synthesis is an important concept for the development of antifungal drugs with high safety. Here, we conduct a high-throughput screen using a C . albicans strain expressing green fluorescent protein-labeled Dpp3 to identify anti-hypha agents by interfering with ergosterol synthesis. The antipyrine derivative H55 is characterized to have minimal cytotoxicity and potent inhibition of C . albicans hyphal formation in multiple cultural conditions. H55 monotherapy exhibits therapeutic efficacy in mouse models of azole-resistant candidiasis. H55 treatment increases the accumulation of zymosterol , the substrate of C-24 sterol methyltransferase (Erg6). The results of enzyme assays, photoaffinity labeling , molecular simulation, mutagenesis , and cellular thermal shift assays support H55 as an allosteric inhibitor of Erg6. Collectively, H55, an inhibitor of the fungal-specific enzyme Erg6, holds potential to treat C . albicans infections.
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BIOCHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 3.978
Yumei Xiao,Yanxia Chen,Ruowei Lu,Yongchao Wang,Cuijuan Wang
A novel hierarchical magnetic zeolitic imidazolate framework-8 material (Hierarchical mZIF-8) is fabricated by using the cetyltrimethylammonium bromide (CTAB) and L -histidine (His) as templates. Comparing to usual magnetic ZIF-8 (mZIF-8), there are not only micropores (1.1 nm) but also new mesopores (23.3 nm) in hierarchical mZIF-8 material. It is the first time that Candida rugosa lipase (CRL) has been immobilized into hierarchical mZIF-8 with significantly higher enzyme loading capacity than mZIF-8. Furthermore, the temperature stability, pH stability and recycling convenience of immobilized CRL are all enhanced compared with free CRL.
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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
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抗感染研究
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药物化学
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