INFECTION GENETICS AND EVOLUTION
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2021
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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.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2024
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IF 3.9
Zhenlong Zhou,Shengli Wang,Penghui Fan,Xiaofeng Meng,Xinyu Cai,Wen Wang,Lin Ma,Hang Ma,Jianyu Su
Candida albicans ( C. albicans ), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans . This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.
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MYCOPATHOLOGIA
·
2025
·Vol. 190
·期 5
·1-14
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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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JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC
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2016
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IF 2.189
Yicheng Bi,Min Yu,Haiyan Zhou,Hua Zhou,Ping Wei
In our study, oleyl oleate was synthesized through enzymatic esterification of oleic acid with oleyl alcohol using Candida rugosa lipase (CRL) immobilized on macroporous resin in a solvent-free system. CRL was immobilized flexibly on the support via aldehyde-dextran, and the effectiveness of aldehyde-dextrans, as cross-linking agents with different molecular weights, was compared and discussed. The impact of various factors, such as different molecular weights of dextran , molar ratio between oleic acid and oleyl alcohol, and the temperature and stability of enzymes, on esterification was investigated as well. Our study indicated that lipase immobilized by 20000 Da dextran yielded the best result. The optimal condition to produce oleyl oleate using immobilized CRL was found in our study and turned out to be molar ratio of 1, reaction temperature of 40 °C, and a 12-h reaction time to reach reaction equilibrium. Under the optimal reaction conditions, a high percentage yield of ester was achieved (92.6%). The immobilized CRL also reached a conversion rate of 86.7% with excellent stability even after 8 cycles.
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MICROBIOLOGICAL RESEARCH
·
2024
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IF 6.1
Ting Fang,Juan Xiong,Xin Huang,Xinyu Fang,Xuqing Shen,Yuanying Jiang,Hui Lu
Strategies aimed at targeting fungal extracellular heat shock protein 90 (eHsp90) using vaccines and antibodies have demonstrated encouraging potential in the prevention and management of invasive fungal diseases (IFDs). However, the precise underlying mechanism by which eHsp90 contributes to the heightened virulence of Candida albicans ( C. albicans ) remains an enigma, awaiting further elucidation. In our current research, we have found that the 47-kDa fragment of C. albicans Hsp90 (CaHsp90), which serves as the primary antigenic determinant, is not degraded within C. albicans cells. Moreover, we have discovered that extracellular CaHsp90 (eCaHsp90) is derived from the components of lysed C. albicans cells. We also generated recombinant CaHsp90 in Escherichia coli , and found that eCaHsp90 spreads beyond the initial C. albicans colonization site, thereby enhancing the overall virulence of the organism. Our results further clarify that eCaHsp90 activates the nuclear factor kappa-B (NF-κB) signaling pathway and upregulates the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3). This upregulation results in the activation of Gasdermin D (GSDMD) and subsequent macrophage pyroptosis, ultimately increasing the virulence of C. albicans . This study provides valuable insights into the mechanism by which eCaHsp90 contributes to the virulence of C. albicans , offering a pharmacological basis for antifungal strategies targeting fungal eHsp90.
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MOLECULES
·
2023
·Vol. 28
·期 24
·8052
·
IF 4.6
Yinzheng Ma,Jinlei Sui,Yan Wang,Wanying Sun,Guohui Yi,Jinyan Wu,Shi Qiu,Lili Wang,Aihua Zhang,Xiaowen He
Infections caused byCandida albicans(C. albicans) and increasing resistance to commonly used drugs lead to a variety of mucosal diseases and systemic infectious diseases. We previously confirmed that the essential oil ofClausena lansium(Lour.) Skeels seeds (CSEO) had antifungal activity againstC. albicans, but the detailed mechanism between the chemical components and antifungal activity is unclear. In this study, a quantitative analysis of five volatile components of CSEO, including sabinene,α-phellandrene,β-phellandrene, 4-terpineol, andβ-caryophyllene, was carried out using the gas chromatography–mass spectrometry (GC–MS) method. Both the broth dilution and kinetic growth methods proved that the antifungal activity of CSEO against fluconazole-resistantC. albicanswas better than that of its main components (sabinene and 4-terpineol). To further investigate the inhibitory mechanism, the transcriptional responses ofC. albicansto CSEO, sabinene, and 4-terpineol treatment were determined based on RNA-seq. The Venn diagram and clustering analysis pattern of differential expression genes showed the mechanism of CSEO and 4-terpineol’s anti-C. albicansactivity might be similar from the perspective of the genes. Functional enrichment analysis suggested that CSEO regulated adherence-, hyphae-, and biofilm-formation-related genes, which may be CSEO’s active mechanism of inhibiting the growth of fluconazole-resistantC. albicans. Overall, we preliminarily revealed the molecular mechanism between the chemical components and the antifungal activity of CSEO againstC. albicans.This study provides new insights to overcome the azole resistance ofC. albicansand promote the development and application ofC. lansium(Lour.) Skeels seeds.Keywords:Clausena lansium(Lour.) Skeels seeds;essential oil;Candida albicans;drug resistance;gas chromatography–mass spectrometry;transcriptomics analysis
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Molecular Catalysis
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2021
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IF 5.062
Chao Xu,Hongbo Suo,Yu Xue,Jing Qin,Hongyue Chen,Yi Hu
Four types of amino acid ionic liquids (AAILs) with chiral structure were used to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity at different temperatures and pH, thermostability, and tolerance to organic solvents of all modified lipases were improved. The composition and configuration of modifiers have great influence on the catalytic performance of the modified lipases. AAILs composed of l -proline exhibited better modification effect than those containing d -proline. The use of [N-AC- l -Pro] [Cl] led to the highest modification degree (47.92 %) of the lipase, which exhibited the highest hydrolytic activity (430.67 U/g), as well as enhanced thermal stability and tolerance to organic solvents. The structure of CALB was characterized by circular dichroism (CD) and fluorescence spectroscopy. It was found that the introduction of a modifier changes the secondary structure of CALB to a certain extent, and the microenvironment around the fluorescent group changed slightly. The structural stability of CALB modified with [N-AC- l -Pro] [Cl] and the mechanism of reaction were studied by molecular dynamics simulations. The molecular dynamics simulations of the native and modified CALB were performed for 20 ns at 300 and 328 K. The simulation results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating a more stable structure for the modified CALB. The root mean square fluctuation (RMSF) calculations showed that the rigidity of the modified CALB and the flexibility of the active center region were both enhanced. The solvent accessibility area (SASA) calculations showed that both hydrophilicity and hydrophobicity of the modified enzyme-protein were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites was also increased. Thus, the modified CALB has enhanced structural stability and higher hydrolytic activity towards the triglyceride substrates.
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Microorganisms
·
2026
·Vol. 14
·期 5
·993
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IF 4.7
Yuwei Xing,Jingru Zhang,Cong Liu,Yang Liu,Jun Wang
Nymphaea candida Presl is a rare and endangered waterlily species, and cultivating robust seedlings suitable for artificial propagation has become a critical issue for the conservation of this species. In this study, Aspergillus sp., an endophytic fungus isolated from the roots of N. candida , showed the capability of solubilizing phosphate and potassium and producing siderophores. The application of Aspergillus sp. significantly increased leaf length, leaf width, leaf number, and root length of N. candida seedlings by 97.83%, 131.37%, 94.12%, and 171.25%, respectively. Meanwhile, Aspergillus sp. application significantly enhanced soil organic matter content, alkali-hydrolyzable nitrogen content, sucrase activity, and peroxidase activity by 6.57%, 31.62%, 23.26%, and 7.53%, respectively. Moreover, Aspergillus sp. enriched beneficial microorganisms including Cyanobium , Aquicella , and Cryptomycota to form a more stable rhizosphere soil microenvironment. Additionally, Aspergillus sp. upregulated genes involved in photosynthesis and photosynthesis–antenna protein pathways in N. candida leaves, with the expression levels of psbA , petG , and psbH significantly increasing by 2.17, 4.48, and 0.28-fold, respectively. Therefore, the endophytic fungus Aspergillus sp. might be a reliable tool for the propagation of N. candida seedlings, which would be helpful for the conservation of this rare and endangered aquatic plant species.
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Advanced Therapeutics
·
2023
·
IF 4.6
Hong Zhang,Yuanfei Zhang,Yiyang Li,Min Hu,Zihan Rong,Lingjie Meng,Xiaofei Zhang,Luan Wen,Xiumin Liang,Zhaopeng Chen,Chengcheng Liu
Vaginal candidiasis caused by Candida albicans is a chronic, recurrent disease that is difficult to treat. Current available antifungal drugs have limited efficacy and cause adverse effects necessitating novel therapeutic options. In this study, a novel metal-organic framework (MOF) containing the sonosensitizer rose bengal (RB) and decorated with silver nanoparticles (AgNPs), Fe–MOF(RB)@AgNPs (MRA), is developed which integrates chemodynamic therapy (CDT) and sonodynamic therapy (SDT) with the long-term antifungal effects of AgNPs into a single nanoscale entity. MRA exhibited low cytotoxicity in mammalian cells and strong catalytic activity for the conversion of H 2 O 2 to •OH under acidic conditions, similar to those found in vaginal candidiasis. When exposed to ultrasound, MRA generated 1 O 2 and offered rapid synergistic fungicidal effects through CDT and SDT, as well as long-lasting antifungal benefits through AgNPs, leading to the complete eradication of drug-resistant C. albicans . Moreover, MRA exhibited 99.999% efficacy against a clinical isolate of drug-resistant C. albicans at 120 µg mL −1 . Hence, MRA has considerable potential for clinical applications in the treatment of drug-resistant C. albicans -induced vaginal candidiasis.
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Pharmaceutics
·
2022
·Vol. 14
·期 9
·1937
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IF 6.525
Chenghua Song,Ruichao Wen,Jiaxuan Zhou,Xiaoyan Zeng,Zi Kou,Jia Zhang,Tao Wang,Pengkang Chang,Yi Lv,Rongqian Wu
The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide,Androctonus amoreuxiAntimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-ResistantStaphylococcus aureus(MRSA) orCandida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.Keywords:antimicrobial peptides;GK-19;skin and soft tissue infections;MRSA;Candida albicans
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 8
·4276
·
IF 4.9
Chenyang Li,Xinxin Qi,Lei Xu,Yuan Sun,Yan Chen,Yuhan Yao,Jun Zhao
This study aimed to investigate the preventive effects of the total polyphenols fromNymphaea candida(NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate LPS-induced lung tissue pathological injury in mice as well as lung wet/dry ratio and MPO activities (p< 0.05). NCTP could significantly decrease the blood leukocyte, neutrophil, monocyte, basophil, and eosinophil amounts and LPS contents in ALI mice compared with the model group (p< 0.05), improving lymphocyte amounts (p< 0.05). Moreover, compared with the model group, NCTP could decrease lung tissue TNF-α, IL-6, and IL-1β levels (p< 0.05) and downregulate the protein expression of TLR4, MyD88, TRAF6, IKKβ, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, NLRP3, ASC, and Caspase1 in lung tissues (p< 0.05). Furthermore, NCTP could inhibit ileum histopathological injuries, restoring the ileum tight junctions by increasing the expression of ZO-1 and occludin. Simultaneously, NCTP could reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Clostridiales and Lachnospiraceae, and enhance the content of SCFAs (acetic acid, propionic acid, and butyric acid) in feces. These results suggested that NCTP has preventive effects on septic ALI, and its mechanism is related to the regulation of gut microbiota, SCFA metabolism, and the TLR-4/NF-κB and NLRP3 pathways.
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Journal of Environmental Chemical Engineering
·
2026
·Vol. 14
·期 4
·123412
·
IF 7.5
Jiahao Ouyang,Yulin Chen,Xiaonuo Li,Jiahao Li,Qiu Xia,Kai Huang,Guangyang Wang,Yong Ye
To address enzyme inactivation upon immobilization and the underutilization of surplus glycerol from biodiesel production, a near-infrared (NIR)-responsive bioconjugate was developed which comprised Candida antarctica lipase B (CALB) immobilized on a CuS/Cu-TCPP support. In this design, Cu-TCPP (a porphyrin-based metal-organic framework) provides a high-surface-area scaffold, CuS nanoparticles act as NIR photothermal converters, and hydrophobic surface modification enhances lipase adsorption. XRD, XPS, SEM, and TEM confirmed the formation of covellite-structure CuS on Cu-TCPP and successful enzyme immobilization. The system achieves a photothermal conversion efficiency of 22.70% (defined as the ratio of heat generated to absorbed laser energy), retains 99.52% of its initial activity at 70 °C, and preserves 74.20% activity after five reuse cycles. During glycerol esterification under NIR irradiation (808 nm) at room temperature, oleic acid conversion reaches 69.2%, representing a 2.42-fold increase compared to the non-irradiated control (28.6%). Bandgap analysis (1.66 eV > 1.53 eV) confirms the absence of reactive oxygen species generation, preventing enzyme oxidative inactivation. This work enables remote, real-time, and precise control of lipase catalysis via localized photothermal heating, offering a green strategy for glycerol valorization.
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