LWT-FOOD SCIENCE AND TECHNOLOGY
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2022
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IF 6.056
Yunhao Lu,Linzi Yang,Yunfeng An,Dayu Liu,Guohua Yang,Qiang He
Candida etchellsii is a predominant strain in Chinese horse bean-chili-paste, a famous and traditional condiment with high salt content. In this study, physiological properties, ester production capacity and gene expression of C. etchellsii under salt stress were investigated, and the results showed that the strain evoked miscellaneous regulations to resist high salt stress. Under salt stress, C. etchellsii would accumulate intracellular glycerol, Na + and K + to balance osmotic pressure. Interestingly, the strain showed much stronger capacity to yield ethyl hexanoate and hexyl acetate after 5% and 20% ( w/v ) NaCl treatment whether in esterification or alcoholysis system. Furthermore, transcriptome data indicated that the genes associated with carbohydrate metabolism and amino acid metabolism had significantly different expression, and their regulations were consistent with the results of physiological analysis. The results obtained in this study could contribute to understand the salt tolerance mechanism of C. etchellsii and provide a theoretical support for its application in traditional food fermentation.
研究领域:
微生物学
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食品科学
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分子生物学
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DOI
高影响因子
Microbial Biotechnology
·
2026
·Vol. 19
·期 3
·e70321
·
IF 6.7
Ziqi Wang,Ziran Wang,Qi Zhang,Yuanyuan Song,Haoying Zhang,Qin Xu,Jianmin Liao,Yuanyuan Lu
While Candida albicans alcohol dehydrogenase I (Adh1) conventionally functions as an alcohol dehydrogenase, this study builds upon previous work to redefine its novel role in regulating hyphal morphogenesis and elucidates the underlying mechanisms. Adh1 knockout strains exhibited hyperfilamentation, suggesting that Adh1 directly regulates true hyphal development, independent of its canonical metabolic activity. Leveraging this phenotype, a ‘reverse screening strategy’ identified 2-hydroxyanthraquinone (HAQ) through high-throughput screening as a potent inhibitor of biofilm formation and hyphal growth by targeting Adh1. Biochemical and structural analyses confirmed HAQ's direct binding to Adh1's F224/A254/Q257 interface. Mechanistically, affinity purification-mass spectrometry revealed Adh1 modulates the SNF1 signalling axis by accelerating SNF1 dephosphorylation via interactions with Bmh1/Ssb1 regulators, thereby inhibiting hyphal conversion. HAQ disrupted these interactions, reducing SNF1 phosphorylation levels in an Adh1-dependent manner. This work establishes Adh1 as both an endogenous SNF1 pathway suppressor and an exogenous drug target, while demonstrating the efficacy of phenotype-driven discovery pipelines. The findings provide a novel antifungal strategy targeting virulence-regulating metabolic enzymes and validate HAQ as a lead compound for therapeutic development against C. albicans pathogenicity. Graphical Based on the ADH1 knockout strain, HAQ was identified through forward/reverse genetic screening of 114 natural products and analysis of protein ligand and protein–protein interactions. With the help of HAQ, a new mechanism for regulating the phosphorylation level of Adh1 –SNF1 has been revealed, in which HAQ binds to Adh1 to release dephosphorylation factors Bmh1 and Ssb1, thereby reducing the phosphorylation level of SNF1 and inhibiting hyphal growth.
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PubMed
高影响因子
Virulence
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2026
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IF 6.8
Yi Zhou,Wenxia Gao,Yuting Feng,Xingyi Tang,Yutong Jin,Jinrong Feng
Transcriptional reprogramming under genotoxic stress is essential for the survival and pathogenesis of Candida albicans. While many DNA damage response (DDR) genes are well-characterized, the functions of pathogen-specific, stress-inducible genes remain poorly understood. Here, we characterized GEI1 (Orf19.3109), a gene significantly induced by genotoxic agents and oxidative stress, which lacks a clear ortholog in Saccharomyces cerevisiae. Interestingly, although GEI1 expression is triggered by DNA damage stress, its deletion does not impair genotoxin tolerance. Instead, the gei1Δ mutant shows increased resistance to oxidative stress, characterized by reduced intracellular reactive oxygen species (ROS) accumulation. Furthermore, loss of GEI1 leads to hyper-secretion of extracellular aspartyl proteases (Saps) and results in a hypervirulence phenotype in the Galleria mellonella infection model. Transcriptomic profiling and CRISPR-interference (CRISPRi) assays revealed that loss of GEI1 function triggers the hyperactivation of antioxidant defenses and protease secretion. We demonstrate that the hypervirulence of the gei1Δ mutant is primarily driven by the transcriptional derepression of SAP1, SAP3, SAP5 and the putative alcohol dehydrogenase ADH4. Repression of these downstream effectors in the gei1Δ background reduced protease secretion and restored virulence to wild-type levels. Overall, our findings uncouple transcriptional induction from conventional DNA repair functions and reveal a novel regulatory checkpoint where GEI1 links genotoxic stress signaling to the suppression of key pathogenic traits, highlighting a complex strategy by which C. albicans balances stress adaptation and virulence control.
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高影响因子
CHINESE CHEMICAL LETTERS
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2026
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IF 9.5
Xiaoming Zou,Hailin Zhang,Jianzhong Zeng,Ligui Wu,Ziyun Yin,Yimei Zeng,Qunyan Zhou,Lingling Rong,Yanbo Zhou,Xubiao Luo
The extensive use of gibberellic acid (GA 3 ) in agriculture leads to residues in agricultural products, raising potential human health concerns, particularly where residue limits are not established. Microbial degradation offers a promising remediation strategy, yet progress is limited by the scarcity of highly efficient degraders and an incomplete understanding of underlying mechanisms. Here, we identify a Candida tropicalis strain (GAJ-2) that achieves 83.63 % GA 3 removal within 120 h, exceeding the efficiencies reported for previously described GA 3 -degrading strains such as Aspergillus niger and Enterococcus mundtii (55.58 %–56.90 % within 5–7 days), and we further validate its residue-removal capacity in representative fruits and vegetables. Mechanistic analyses indicate that viable-cell-mediated GA 3 biotransformation by GAJ-2 mainly involves dehydroxylation, decarboxylation, and cleavage of the tetracyclic diterpenoid scaffold. These transformations are rationalized by the electronic distribution of oxygen-bearing functional groups and the electrophilic nature of C11 and adjacent positions in GA 3 . Multi-omics analyses further reveal enhanced energy metabolism and catalytic functions, together with efflux-pump regulation, and show a strong association between GA 3 catabolism and the upregulation of key enzymes ( e.g. , decarboxylases and dehydrogenases). Docking-based interaction profiling suggests that GA 3 associates with key proteins primarily through noncovalent interactions, including hydrogen bonding, van der Waals contacts, and electrostatic effects. Collectively, this work provides multi-level experimental and computational evidence supporting a plausible framework for GA 3 biodegradation by GAJ-2 and informs improved strategies for GA 3 pollution control.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Sijin Hang,Bingchen Jiang,Wanqian Li,Xiaojing Xu,Liping Xu,Juan Xiong,Yuanying Jiang,Hui Lu
Biofilms formed by Candida albicans pose significant challenges in clinical settings, particularly in medical device-related infections and recurrent candidiasis, due to their inherent resistance to azoles. Consequently, there is an urgent need to identify novel compounds that can potentiate the antifungal activity of azoles against C. albicans biofilms. In this study, we utilized a drug repositioning approach to perform high-throughput screening of a library of 2,372 Food and Drug Administration (FDA)-approved compounds, identifying pramocaine hydrochloride (pramocaine) as a potent azole potentiator with low cytotoxicity. Pramocaine significantly enhanced the antifungal activity of fluconazole (FLC) against C. albicans biofilms both in vitro (via biofilm inhibition assays) and in vivo (using a mouse subcutaneous catheter infection model), and exhibited broad-spectrum efficacy against other clinically relevant Candida and Cryptococcus species. Mechanistically, pramocaine targets Erg12, a key enzyme in the farnesyl pyrophosphate pathway, to inhibit ubiquinone biosynthesis and elevate mitochondrial reactive oxygen species (ROS) production. This leads to impaired mitochondrial function, reduced C. albicans hyphal elongation, biofilm thickness, and extracellular matrix secretion, thereby sensitizing C. albicans biofilms to FLC. As an FDA-approved compound, pramocaine offers promising translational potential for treating azole-resistant biofilm infections. This research introduces a novel strategy to potentiate the antifungal efficacy of FLC against C. albicans biofilms by targeting Erg12-mediated ubiquinone biosynthesis.
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PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
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2026
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IF 5.5
Duo Han,Xin Yang,Xiao Hui Zhao,Yu Xing Zheng,Yue Jian Mao,Xiao Wei Zheng,Juan Yang,Jia Lun Chen
BackgroundVaginal candidiasis (VC), mainly triggered by Candida species, ranks among the most‑common reproductive‑tract infections worldwide. Over‑utilization of antibiotics and antifungal medicines aggravates fungal drug‑resistance, which makes it imperative to explore novel alternative therapies. This work intended to investigate the anti‑Candida‑albicans activity of Lacticaseibacillus paracasei VCare‑360.MethodsThe in‑vitro capacities of the strain to produce hydrogen peroxide and lactic acid and its antifungal activity were tested. A vaginal‑epithelial‑cell model was adopted to evaluate bacterial competitive adhesion and the regulation of pro‑inflammatory cytokine secretion. A mouse VC animal‑model was constructed to assess vaginal mucosal repair, inflammatory‑factor levels, myeloperoxidase activity, as well as vaginal and faecal microbiota composition after probiotic intervention.ResultsL. paracasei VCare‑360 competed against C. albicans for vaginal‑epithelial‑cell adhesion and suppressed fungal colonization. It lowered the release of pro‑inflammatory cytokines in-vitro. In mice, this probiotic alleviated vaginal epithelial exfoliation, repaired damaged vaginal mucosa and relieved local inflammation (p < 0.05). It also decreased pro‑inflammatory cytokine concentrations and myeloperoxidase activity in blood and vaginal tissue. Sequencing results demonstrated that VCare‑360 enriched the relative abundance of Lactobacillus and cut down vaginal Escherichia-Shigella.ConclusionLacticaseibacillus paracasei VCare‑360 can inhibit C. albicans infection, modulate vaginal flora and restore the vaginal mucosal barrier, and serves as a promising probiotic candidate for the treatment of Candida‑induced vaginal candidiasis.
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高影响因子
INTERNATIONAL DENTAL JOURNAL
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2025
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IF 3.7
Jiadi Shen,Chenyu Weng,Shuxian Zhu,Wanjing Chen,Xuening Xiong,Xin Wei
Objectives Candida albicans ( C. albicans ) biofilms are well-known to be resistantto various antifungal agents. Autophagy is crucial for adapting to changes in nutrition conditions. Protein phosphatase 2A (PP2A) is prominent in regulating physiological processes, possibly related to autophagy-related (ATG) protein phosphorylation. This study hypothesizes that PP2A affects biofilm formation and drug resistance of C. albicans via autophagy induction. Materials and methods The expressions of PP2A catalytic subunit coding gene PPH21 were compared. The mutant strain ( pph21 Δ/Δ) was constructed and the biofilm was treated with autophagy activator (rapamycin, Rap). The biofilm formation, drug susceptibility and oxidative stress levels were examined. The autophagic activity was detected, along with the autophagosomes observed. The therapeutic efficacy of the antifungal agents was estimated on the mice model of C. albicans oral infection. Results PPH21 was associated with C. albicans biofilm formation and drug resistance. Autophagy activation by rapamycin can induce increased autophagy levels, while it was hindered in pph21 Δ/Δ. Besides, the protein levels of Atg13 and Atg1 were significantly down-regulated in pph21 Δ/Δ+Rap ( P < .01), along with its decreased regulatory capacity to oxidative stress. Autophagy activation can promote biofilm formation and improve drug resistance, while the absence of PPH21 may prevent the enhancement of drug resistance. Autophagy activation reduced the efficacy of antifungal agents in treating oral C. albicans infection in mice, among which pph21 Δ/Δ presented better therapeutic effects. Conclusion PP2A is important in the autophagy induction of C. albicans by participating in Atg13 phosphorylation, followed by Atg1 activation, further affecting its biofilm formation and drug resistance. Clinical relevance PP2A-induced autophagy may be a potential regulatory mechanism of C. albicans drug resistance. This appears to be a promising therapeutic strategy for managing C. albicans -related infectious diseases.
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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细胞生物学
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医学真菌学
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PubMed
高影响因子
Food Bioscience
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2025
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IF 5.9
Zhenlong Zhou,Kun Lan,Zizhen Wang,Pengzhen Li,Penghui Fan,Jianyu Su
Natural plant-derived molecules are emerging as promising alternatives to chemical preservatives. Among these, the phytochemical borneol has been shown to inhibit the growth of common foodborne bacteria, but its antifungal activity and underlying mechanisms remain largely unexplored. This study aims to investigate the antifungal properties of borneol and its mechanisms of action against Candida albicans , a foodborne fungus that poses a significant threat to food safety. The results demonstrated that the antifungal efficacy of borneol against Candida albicans was concentration-dependent at the tested time points. Transcriptomic analysis and electron microscopy revealed that borneol primarily targets cell membranes to exert its antifungal effects. Further experiments showed that borneol specifically binds to membrane proteins, particularly chitin synthases 1, 2, and 3, inhibiting chitin biosynthesis and disrupting cellular integrity. Molecular dynamics simulations indicated that borneol diffuses passively from the aqueous phase into the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphorylcholine bilayer membrane, where it preferentially aggregates in hydrophobic regions, altering the bilayer's thickness and fluidity. Notably, this aggregation likely plays a key role in influencing the structure and function of membrane proteins. Lipidomics analysis further confirmed that borneol disrupts cell membrane integrity, leading to the loss of glycerophosphocholines and glycerophosphoethanolamines lipids. As borneol alters membrane structure and function, it also induces the intracellular accumulation of reactive oxygen species, resulting in membrane lipid peroxidation. In conclusion, these findings provide a theoretical foundation for the potential use of borneol in the food industry to prevent and control pathogenic fungal contamination.
研究领域:
微生物学
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植物药理学
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分子生物学
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食品安全
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计算生物学
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高影响因子
MATERIALS TECHNOLOGY
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2024
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IF 2.9
Li Liu,Siyu Li,Detai Shi,Wei Zhu,Shuangshuang Zhang,Chengzhi Zhou,Tiangui Zhao,Xiaolong Li,Qifu Bao,Jianer Zhou
In this study, hydrothermal-calcination method was employed to synthesize pure vanadium oxide and zinc doped vanadium oxide powders. The crystal structure, morphology, chemical state and light absorption properties of the powders were also thoroughly analyzed. The antimicrobial effect against Candida albicans was evaluated by the circle of inhibition method and plate colony counting method. This study reveals the antibacterial mechanism of oxygen defects generating reactive oxygen species, leading to oxidative stress damage. This study not only demonstrates the potential of vanadium oxides as an efficient antimicrobial agent, but also provides a strong experimental basis and theoretical support for the design and optimization of novel antimicrobial materials by modulating the defect engineering of the materials. This finding provides a new perspective for the development of antimicrobial strategies against microorganisms and has important application prospects for the clinical treatment of Candida albicans infections.
研究领域:
微生物学
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材料科学
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医学
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高影响因子
Journal of Materials Chemistry B
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2024
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IF 6.1
Hao Li,Yangyang Shi,Hui Chen,Jingou Liang,Shiyong Zhang,Bolei Li,Jing Chen,Mingyun Li,Xian Peng,Xue-Dong Zhou,Biao Ren,Lei Cheng
The scarcity of antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, Dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived C=C double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, tertiary amine of DMAEM protonates into a cationic fungicide sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting CHK1 two component system in C. albicans. At neutral pH, methacrylate-derived C=C double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering C. albicans extracellular vesicles. These findings support the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.
研究领域:
药学
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微生物学
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生物技术
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PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
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2019
·Vol. 126
·期 1
·102-112
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IF 2.683
Lin W.,Yuan D.,Deng Z.,Niu B.,Chen Q.
ObjectivesIn our previous research, we have developed a new combination disinfectant, glutaraldehyde‐didecyldimethylammonium bromide (GD). It was verified that GD had a strong effect on both Escherichia coli and Staphylococcus aureus. In this work, Candida albicans was selected as an object, and it could be killed by GD. We aimed to investigate the cellular and molecular mechanism of GD effecting on C. albicans.Methods and ResultsThe results of sterilization experiment indicated that GD was effective on C. albicans. Flow cytometry and atomic absorption spectrometry were applied to detect cell membrane damage of C. albicans. Luciferase reaction and Bradford method were carried out to detect ATP content and protein quantitation. Transmission electron microscopy was used for intracellular organelles morphological observation. In order to study changes in mitochondrial membrane potential, Rh 123 was used as an indicator. DNA conformation analysis was performed by molecular modelling and circular dichroism. The results indicated that membrane permeability was increased rapidly owing to GD effect, and the leaked K+ and Mg2+ were about 12·1 and 12·4 times those of the control, respectively, at 10 min after GD treatment. Simultaneously, ATP and protein also leaked rapidly out of the cell. Mitochondrial membrane potential was destroyed, succinic dehydrogenase activity was significantly decreased and DNA conformation was changed because of GD action.ConclusionsGlutaraldehyde‐didecyldimethylammonium bromide disinfected C. albicans through distorting cell membrane integrity and permeability, disturbing the intracellular homeostasis by intracellular substances leakage, especially K+, Mg2+, ATP and protein, causing electrolyte imbalance of mitochondria, changing DNA structure, which finally led to cell death.Significance and Impact of the StudyThis study focused on the cellular and molecular mechanism of GD as a disinfectant against C. albicans. It is important to provide theoretical support to GD against Candida albicans in practical application.
研究领域:
微生物学
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分子生物学
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细胞生物学
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PubMed
高影响因子
RESEARCH IN MICROBIOLOGY
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2025
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IF 3.4
Haoying Zhang,Qi Zhang,Ting Zuo,Ziqi Wang,Jianmin Liao,Yuanyuan Lu
Candida albicans is an opportunistic pathogen, and the formation of its biofilm makes it resistant to traditional antifungal therapy. Anthraquinones have universal antibacterial activity. We evaluated the inhibitory effects of 2-chloromethyl anthraquinone on C. albicans adhesion, mycelial morphology transformation, and biofilm formation. The results showed that 2-chloromethyl anthraquinone could inhibit C. albicans adhesion, mycelium formation, and biofilm formation in a dose-dependent manner at 2 μg/mL. In addition, 2-chloromethyl anthraquinone significantly inhibited the expression of biofilm formation-related genes in C. albicans , including ALS1 , CPH1 , ECE1, HWP1 , TEC1 , BCR1 , and UME6 . In addition, Ras1-cAMP-Efg1 pathway-related genes ( RAC1 , CYR1 , and TPK2) were also significantly down-regulated, indicating that the inhibitory effect of 2-chloromethyl anthraquinone on C. albicans biofilms may be related to the Ras1-cAMP-Efg1 signaling pathway. In summary, the results of this study confirmed the inhibitory mechanism of 2-chloromethyl anthraquinone on the virulence factors of C. albicans , which laid a theoretical foundation for its use as an anti-biofilm agent against C. albicans .
研究领域:
微生物学
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真菌学
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药理学
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PubMed
高影响因子
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