Food Bioscience
·
2026
·
IF 5.9
Qingyan Guo,Chuncheng Yi,Chengxi Yang,Jingjing Zhao,Jiabao Peng,Yukun Huang,Wenyu Yang
This study aimed to explore Huangshui , a byproduct of Baijiu fermentation, as a novel source of antimicrobial peptides (AMPs). Through ultrafiltration, semi-preparative high-performance liquid chromatography (HPLC), and reversed-phase (RP-HPLC), a fraction with potent antimicrobial activity was isolated. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis identified 27 peptide sequences, among which only the heptapeptide HS-4 (sequence: ALTNPTT) exhibited significant activity against Candida albicans . HS-4, characterized by a net charge of zero and a disordered random-coil conformation, demonstrated a minimum inhibitory concentration (MIC) of 64 μmol/L and a minimum fungicidal concentration (MFC) of 256 μmol/L against C. albicans . It showed excellent biocompatibility (negligible hemolysis and cytotoxicity) and stability under various pH, salt, and serum conditions, though its activity was reduced by high temperatures (>100 °C), divalent metal ions, and enzymatic treatment. Mechanistic studies using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and nucleic acid leakage assays revealed that HS-4 exerts its fungicidal effect by disrupting the cell wall and membrane integrity of C. albicans , leading to content leakage and cell death. These findings highlight the uniqueness of HS-4 as a food-derived AMP and its potential as a natural biopreservative against C. albicans contamination in the food industry.
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Catalysts
·
2021
·Vol. 11
·期 12
·1463
·
IF 4.146
Honghai Wang,Wenda Yue,Shuling Zhang,Yu Zhang,Chunli Li,Weiyi Su
Silica xerogels have been proposed as a potential support to immobilize enzymes. Improving xerogels’ interactions with such enzymes and their mechanical strengths is critical to their practical applications. Herein, based on the mussel-inspired chemistry, we demonstrated a simple and highly effective strategy for stabilizing enzymes embedded inside silica xerogels by a polydopamine (PDA) coating through in-situ polymerization. The modified silica xerogels were characterized by scanning and transmission electron microscopy, Fourier tranform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and pore structure analyses. When the PDA-modified silica xerogels were used to immobilize enzymes ofCandida antarcticalipase B (CALB), they exhibited a high loading ability of 45.6 mg/gsupport, which was higher than that of immobilized CALB in silica xerogels (28.5 mg/gsupport). The immobilized CALB of the PDA-modified silica xerogels retained 71.4% of their initial activities after 90 days of storage, whereas the free CALB retained only 30.2%. Moreover, compared with the immobilization of enzymes in silica xerogels, the mechanical properties, thermal stability and reusability of enzymes immobilized in PDA-modified silica xerogels were also improved significantly. These advantages indicate that the new hybrid material can be used as a low-cost and effective immobilized-enzyme support.Keywords:Candida antarcticalipase B;silica xerogel;enzyme immobilization;polydopamine;modification
研究领域:
生物化学
·
材料科学
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JOURNAL OF MEDICINAL CHEMISTRY
·
2012
·
IF 5.248
Yu-Ting Lee,Chang-Jun Cui,Eve W. L. Chow,Nason Pue,Thierry Lonhienne,Jian-Guo Wang,James A. Fraser,Luke W. Guddat
The sulfonylurea herbicides exert their activity by inhibiting plant acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway. It has previously been shown that if the gene for AHAS is deleted in Candida albicans, attenuation of virulence is achieved, suggesting AHAS as an antifungal drug target. Herein, we have cloned, expressed, and purified C. albicans AHAS and shown that several sulfonylureas are inhibitors of this enzyme and possess antifungal activity. The most potent of these compounds is ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl)carbamoyl)sulfamoyl)benzoate (10c), which has a Ki value of 3.8 nM for C. albicans AHAS and an MIC90 of 0.7 μg/mL for this fungus in cell-based assays. For the sulfonylureas tested there was a strong correlation between inhibitory activity toward C. albicans AHAS and fungicidal activity, supporting the hypothesis that AHAS is the target for their inhibitory activity within the cell.
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Vaccines
·
2023
·Vol. 11
·期 10
·1521
·
IF 7.8
Zirun Zhao,Ying Sun,Mingchun Li,Qilin Yu
The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed by transforming theEscherichia colichassis using a de novo synthetic fragment encoding the protein mChEap1 that was composed of theE. coliOmpA peptide, the fluorescence protein mCherry, theCandida albicansadhesin Eap1, and the C-terminally transmembrane region. The EmEAP1 cells highly exposed the mChEap1 on the cell surface under IPTG induction. The fungal vaccine was then prepared by mixing the EmEAP1 cells with aluminum hydroxide gel and CpG. Fluorescence quantification revealed that the fungal vaccine was stable even after 112 days of storage. After immunization in mice, the vaccine resided in the lymph nodes, inducing the recruitment of CD11c+dendritic cells. Moreover, the vaccine strongly activated the CD4+T splenocytes and elicited high levels of anti-Eap1 IgG. By the prime-boost immunization, the vaccine prolonged the survival time of the mice infected by theC. albicanscells and attenuated fungal colonization together with inflammation in the kidneys. This study sheds light on the development of synthetic biology-based fungal vaccines for the prevention of life-threatening fungal infections.Keywords:fungal vaccine;systemic fungal infection;Candida albicans;adhesin;synthetic biology;protection
研究领域:
微生物学
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免疫学
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合成生物学
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疫苗学
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2021
·Vol. 102
·期 5
·1812-1822
·
IF 3.639
Wenyi Chen,Li Xu,Nanjing Zhong
BACKGROUND Enzymatic esterification is attracting for particular high-acid oil deacidification. In this study, Candida antarctica lipase B (CALB) was encapsulated into a series of nucleotide-hybrid metal coordination polymers (CPs), which were constructed by guanosine 5′-monophosphate (GMP) and various metals. RESULTS We here found that, most of the present CPs encapsulated CALB (CALB@CPs) samples were highly selective for esterification while poor in glycerolysis reaction. They exhibited quite poor performance in glycerolysis, with triacylglycerols (TAGs) conversion lower than 5%, despite this considerable enzymatic hydrolysis activities were observed. However, they (most of them) showed good performance in esterification of fatty acids and glycerol for TAG synthesis. In addition, the GMP/Tb (CPs constructed by GMP and Tb 3+ ) encapsulated CALB (CALB@GMP/Tb) transformed over 98% of oleic acid into glycerides in the high-acid oil deacidification process, and TAG content from 87 to 89% was obtained. Moreover, the CALB@GMP/Tb showed good reusability in the esterification system. CONCLUSION The present CALB@CPs samples are selective for esterification and suitable for high-acid oils deacidification. This work provides a new system for enzymatic selectivity improvement study. © 2021 Society of Chemical Industry.
研究领域:
生物化学
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酶工程
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催化化学
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Future Microbiology
·
2020
·
IF 2.907
Ying Gong,Siwen Li,Weixin Wang,Yiman Li,Wenli Ma,Shujuan Sun
Aim: To evaluate whether chelerythrine (CHT) exhibited antifungal activity against Candida albicans in vitro and in vivo and to explore the underlying mechanisms. Materials & methods: Broth microdilution assay and Galleria mellonella model were used to evaluate the antifungal effect in vitro and in vivo, respectively. Mechanism studies were investigated by morphogenesis observation, Fluo-3/AM, DCFH-DA and rhodamine6G assay, respectively. Results: CHT exhibited antifungal activity against C. albicans and preformed biofilms with minimum inhibitory concentrations ranged from 2 to 16 μg/ml. Besides, CHT protected G. mellonella larvae infected by C. albicans. Mechanisms studies revealed that CHT inhibited hyphal growth, increased intracellular calcium concentration, induced accumulation of reactive oxygen species and inhibited drug transporter activity. Conclusion: CHT exhibited antifungal activity against C. albicans.
研究领域:
微生物学
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药理学
·
分子生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 10
·4478
·
IF 5.6
You-Quan Ma,Lan Lin
Candida albicansis the causal agent of invasive candidiasis, which might be lethal in immunocompromised patients. Biofilm formation is considered a key virulence factor ofC. albicansand is associated with its elevated resistance to antifungals.C. albicansand bacteria likeE. coliare frequently found to form mixed biofilms on biotic or abiotic surfaces, rendering them more refractory to existing antifungals. To investigate howE. coliendogenous indole interplaying with exogenous IAA exerts modulatory effects on dual-species biofilm withC. albicans, anE. colistrain deficient in the indole biosynthetic genetnaAwas constructed, and the enzyme TnaA inhibitor was administered to block the indole production inE. colimonoculture and/orE. coli–C. albicansdual culture. Phenotypic assay revealed that indole deficiency attenuatedE. colimono-species biofilm by 12% (tnaA∆ versus WTE. coli), and the lack of indole in theE. colicell-free culture filtrate abolished the ability to promoteC. albicansbiofilms, evidenced by the fact that the treatment with WTE. coliculture supernatants exhibited a 1.7-fold promotive effect, while treatment withtnaA∆ displayed no significant difference from the broth control towardsC. albicansbiofilms. Furthermore, impairedE. coliindole production might disruptE. coli–C. albicansbiofilm, as examined by confocal laser scanning microscopy (CLSM). Moreover, indole-3-acetic acid (IAA) was found to exhibit more potent biofilm-modulatory activity than indole by CLSM imaging with dual biofilms of WTE. coli–C. albicans, in contrast to those ofE. coli tnaA∆–C. albicanspost-supplemented with exogenous IAA. This study provides evidence for indole as a signaling molecule mediating bacterial–fungal communication during mixed-biofilm formation. Indole and its derivatives, particularly in combination with existing antifungals, have potential in the development of anti-biofilm strategies to eradicate refractory fungal infections.
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Advanced Science
·
2026
·
IF 14.1
Yanyu Su,Yi Li,Meng Xiao,Dan Guo,David S. Perlin,Erika Shor,Yingchun Xu,Yingxing Li
Antifungal heteroresistance has emerged as a clinical challenge across diverse species. In Candida glabrata , however, it has rarely been reported. Here, we characterized heteroresistance in a multicenter collection of 156 C. glabrata isolates, revealing a 25% prevalence with caspofungin specificity and 37°C dependent phenotypes. Transcriptomic profiling of the heteroresistant subpopulation under escalating drug pressure revealed an adaptive program centered on cell cycle and cell wall integrity, including several members of the calcineurin pathway. Mechanically, we identified that the phenotype was abolished by pharmacological inhibition or Δ cnb1 , Δ crz1 genetic deletion, confirming the regulatory role of calcineurin. Crucially, heteroresistance functioned as a reservoir for resistance, with in vitro descendant strains spanning a spectrum of MIC alterations. Mechanistically, we found the heteroresistance phenotype mostly independent of aneuploidy. To decipher the genetic basis, we applied an unbiased machine-learning framework to genomic data, which not only identified the canonical FKS2_F659del mutation but also prioritized novel candidate PIR2_G149_I167del , demonstrating its power to uncover drivers of resistance from complex datasets. In summary, our study established a stepwise model of heteroresistance in C. glabrata , wherein calcineurin serves as a master regulator that promotes a resistance reservoir, revealing a potential vulnerability that could be exploited to prevent treatment failure.
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Microorganisms
·
2025
·Vol. 13
·期 9
·2093
·
IF 4.2
Jiadi Shen,Yuzhi Li,Haochen Miao
Candida albicans(C. albicans) biofilms exhibit enhanced resistance to conventional antifungal agents; however, the underlying pathogenic mechanisms warrant deeper exploration. Protein phosphatase 2A (PP2A), especially its catalytic activity, is crucial for maintaining physiological balance. This study focused on the role of the PP2A catalytic subunit coding genePPH21in biofilm formation and drug resistance ofC. albicans. The mutant strain (pph21Δ/Δ) was generated and identified. The oxidative stress was detected by the reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The autophagic activity was evaluated, and the autophagosomes were observed by transmission electron microscopy (TEM). The biofilm formation was measured by XTT reduction assay, crystal violet (CV) staining, and scanning electron microscopy (SEM). The susceptibility to antifungal agents was examined by XTT reduction assay and spot assay. Additionally, the antioxidant N-acetylcysteine (NAC) was applied to clarify the regulatory effect ofC. albicansautophagy on oxidative stress. The pathogenicity ofPPH21in oralC. albicansinfection was evaluated through in vivo experiments. We found thatPPH21deletion led to increased oxidative stress and autophagic activities, but it can be reversed by the application of NAC. Moreover,PPH21deletion also impaired the biofilm formation ability and reduced resistance to antifungal agents. Our findings revealed thatPPH21is involved in both virulence and stress adaptation ofC. albicans.
研究领域:
微生物学
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分子生物学
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医学真菌学
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药理学
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细胞生物学
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Cell Chemical Biology
·
2026
·Vol. 33
·期 2
·227-240
·
IF 9
Jinyao Chen,Ming Zhang,Yeji Wang,Zhiyu Xie,Fei Yang,Hongjun Yu,Di Zhang,Min Fang,Xiaoyi Luan,Xueyang Jin,Xue Wang,Yanan Qiao,Shicun Zheng,Xiuyun Li,Wenqiang Chang,Hongxiang Lou
The overexpression of drug exporters is a well-known mechanism driving antifungal drug resistance. Here, we investigate that converting the exporter to function as a drug importer provides an alternative approach to combat drug resistance. Using high-throughput screening, we identified quaternary ammonium compounds exhibiting hypersensitivity in Candida albicans strains overexpressing MDR1 . Further experiments involving CRISPR-Cas9-mediated deletion in C. albicans , heterologous expression of Ca Mdr1 in Saccharomyces cerevisiae and construction of Ca Mdr1-containing proteoliposomes confirmed Mdr1 acts as an importer of MKT-077, a potent cyanine derivative highly selective against MDR1 -overexpressing strains. By combining computational simulations and the site-directed mutagenesis, critical residues within the transmembrane domains of Ca Mdr1 involved in MKT-077 import were further identified. Moreover, MKT-077 exhibited therapeutic efficacy in Galleria mellonella infected with Mdr1-overexpressing C. albicans . This work opens an avenue to convert drug resistance into drug sensitivity-a paradigm-shifting strategy in antifungal drug discovery.
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Pathogens and Disease
·
2017
·Vol. 75
·期 6
·
IF 2.335
Liao Hong,Liu Shanling,Wang He,Su Hang,Liu Zhenjun
Histatin5 (Hst-5) is a member of the histatin family of antimicrobial peptides secreted by human parotid and submandibular glands. With the natural antibacterial activity, it plays an important role in the first-line barrier of oral cave against pathogens, especially for the fungal intrusion. In this study, we explored the utility of Hst-5 in the treatment of vulvovaginal candidiasis, a common condition of women of the childbearing age. We used a synthesized Hst-5 over five consecutive days as the topical treatment in a murine model of vulvovaginal candidiasis. According to the fungal colony counts, fungal burden in the vagina lavage dropped remarkably after treatment with Hst-5. Furthermore, cytological analysis of the lavage fluid indicated that the number of cast-off cells including cornified epithelial cells and inflammatory cells also decreased; histological evaluation of the vagina tissue revealed less fungi adhering to the vaginal wall in treated animals than in controls. Combined, these results suggested for the first time the potential utility of Hst-5 as a topical treatment for vulvovaginal candidiasis, uncovering the possibility of exploiting the natural antibiotic peptides in other aspects.
研究领域:
医学
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微生物学
·
妇科学
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Inorganics
·
2023
·Vol. 11
·期 11
·429
·
IF 2.9
Li Liu,Siyu Li,Detai Shi,Qifu Bao,Tiangui Zhao,Wei Zhu,Xiaolong Li,Jianer Zhou
The emergence of drug resistance due to the overuse of antibiotics has made the prevention and treatment of invasive fungal infections caused byCandida albicans(C. albicans) a great challenge. Oxygen vacancy-rich inorganic materials show great promise in the antimicrobial field due to their unique physicochemical properties. Defect engineering can significantly optimize the electronic structure of inorganic materials to further enhance their antimicrobial activity. We designed oxygen vacancy defect-rich V6O13powders using the hydrothermal-calcination method and investigated their anti-C. albicansactivity. The results showed that the stronger antibacterial activity is attributed to the fact that the optimized V6O13powder oxygen vacancy defects induced a reduction reaction of dissolved oxygen in the environment, which produced ROS with strong oxidative properties, causing damage to the wall membrane ofC. albicansand leakage of intracellular material. The minimum inhibitory concentration (99% or more inhibition) of V6O13powders is 4 mg/mL. This work not only provides a facile method for constructing oxygen-rich vacancies in V6O13powders, but also provides new insights into the potential of inorganic materials optimized by defect engineering for efficient antimicrobial activity.
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