BMC MICROBIOLOGY
·
2015
·Vol. 15
·期 1
·171
·
IF 2.729
Wan Lei,Luo Gang,Lu Haibin,Xuan Dongying,Cao Hong,Zhang Jincai
Background Hemolysins are crucial virulence factors which help pathogens to survive and persist in the host. This study investigated whether common electrolytes will affect the hemolysins of Candida species. The hemolysins from 25 Candida isolates were investigated using a plate specially designed for Candida species in the presence of three electrolytes, CaCl 2 , NaCl and KCl, at different concentrations. The hemolytic activity was determined after 48 h and the hemolytic index was calculated. Results All three electrolytes caused a decrease in the hemolytic activity. Significant differences existed between varying concentrations of NaCl, while no significant differences existed for the CaCl 2 and KCl groups. Additionally, the peripheral hemolytic index was highly correlated with the hemolytic index ( r = 0.656, p < 0.001). Conclusions Our findings indicate that electrolytes reduce hemolysis by Candida species and a correlation exists between the peripheral hemolytic index and the translucent hemolytic index.
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Microbiology Spectrum
·
2022
·Vol. 10
·期 4
·
IF 9.043
Liping Li,Hui Lu,Xuan Zhang,Malcolm Whiteway,Hao Wu,Shanlun Tan,Jianye Zang,Shujuan Tian,Cheng Zhen,Xianlei Meng,Wanqian Li,Dazhi Zhang,Min Zhang,Yuanying Jiang
Baicalein (BE) is a promising antifungal small-molecule compound with an extended antifungal spectrum, good synergy with fluconazole, and low toxicity, but its target protein and antifungal mechanism remain elusive. In this study, we found that BE can function against Candida albicans by disrupting glycolysis through targeting Eno1 and inhibiting its function. Eno1 acts as a key therapeutic target of the drug, as BE had no antifungal activity against the eno1 null mutant in a Galleria mellonella model of C. albicans infection. To investigate the mechanism of action, we solved the crystal structure of C. albicans Eno1(CaEno1) and then compared the difference between this structure and that of Eno1 from humans. The predicted primary binding site of BE on CaEno1 is between amino acids D261 and W274, with D263, S269, and K273 playing critical roles in the interaction with BE. Both positions S269 and K273 have different residues in the human Eno1 (hEno1). This finding suggests that BE may bind selectively to CaEno1, which would limit the potential for side effects in humans. Our findings demonstrate that Eno1 is a target protein of BE and thus may serve as a novel target for the development of antifungal therapeutics acting through the inhibition of glycolysis.IMPORTANCE Baicalein (BE) is a promising antifungal agent which has been well characterized, but its target protein is still undiscovered. The protein Eno1 plays a crucial role in the survival of Candida albicans. However, there are few antifungal agents which inhibit the functions of Eno1. Here, we found that BE can function against Candida albicans by disrupting glycolysis through targeting Eno1 and inhibiting its function. We further solved the crystal structure of C. albicans Eno1(CaEno1) and predicted that the primary binding site of BE on CaEno1 is between amino acids D261 and W274, with D263, S269, and K273 playing critical roles in the interaction with BE. Our findings will be helpful to get specific small-molecule inhibitors of CaEno1 and open the way for the development of new antifungal therapeutics targeted at inhibiting glycolysis.
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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结构生物学
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Virulence
·
2026
·
IF 6.8
Xueting Wan,Yuan Wu,Qi Yang,Ruolan Wu,Ti Chen,Zhen Luo
The synergistic interaction between Staphylococcus aureus and Candida albicans exacerbates polymicrobial infection severity and mortality compared to monomicrobial infections. C. albicans metabolism is known to enhance S. aureus virulence, whereas the role of S. aureus metabolic reprogramming in this cross-species synergy remains poorly defined. In this study, we demonstrate that C. albicans remodels S. aureus glycolytic pathways, thereby increasing its virulence in glucose-rich environments. C. albicans triggers metabolic reprogramming in S. aureus, characterized by a reduction of lactate and accumulation of upstream glycolytic intermediates, including 3-phosphoglycerate, 2-phospho-D-glycerate, and phosphoenolpyruvate. The metabolic reprogramming phenotype is glycolysis-dependent, which is evidenced by 2-deoxy-D-glucose-mediated inhibition of virulence enhancement. Addition of exogenous lactate lowers extracellular pH and reduces the hemolytic activity of S. aureus-C. albicans co-cultures. Inhibition of lactate dehydrogenase by oxamate or extracellular alkalinization with sodium hydroxide significantly increases hemolysis in S. aureus mono-cultures. S. aureus-C. albicans co-infections promote inflammatory cell infiltration but do not affect the quantity of S. aureus, indicating that increased toxin levels, rather than bacterial quantity, drive the enhanced virulence. Collectively, these findings indicate that C. albicans enhances S. aureus virulence through metabolic reprogramming. Targeting lactate metabolism or glycolytic intermediates may disrupt this cooperative interaction, offering a novel therapeutic strategy against these polymicrobial infections.
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JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Yaxuan Yue,Jing Liu,Chen Li,Fengfeng Chen,Cheng Yang,Bingtian Zhao
Candida albicans is one of the major sources of fungal infections that can lead to life-threatening systemic infections. However, effective control of C. albicans remains a great challenge. Herein, this study aimed at investigating the antifungal effect of a combination of two natural compounds, pinosylvin (PIN) and sanguinarine (SAN), against C. albicans . In order to investigate the antifungal effect and mechanism of the combination of PIN and SAN, antimicrobial assay, time-kill assay, biofilm formation assay, cell membrane integrity assay, and reactive oxygen species (ROS) assay were performed. The results showed that the combination of PIN and SAN was more effective against C. albicans than PIN or SAN alone. PIN and SAN could jointly inhibit biofilm formation and thus attenuate C. albicans adhesion and colonization ability. PIN mainly targeting the cell membrane while SAN mainly inducing the cell to produce large amounts of ROS. Besides, PIN promoted the entry of SAN into C. albicans . Finally, the hemolysis experiment demonstrated that the combination of PIN and SAN is biocompatible. Taken together, the combination of PIN and SAN enhanced the antifungal effect against C. albicans , which has a broad application prospect in the control of C. albicans .
研究领域:
微生物学
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药理学
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医学
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Cell Host & Microbe
·
2024
·
IF 20.6
Xuemei Wang,Shuang Zhou,Xiaomin Hu,Chuan Ye,Qixing Nie,Kai Wang,Sen Yan,Jun Lin,Feng Xu,Meng Li,Qing Wu,Lulu Sun,Bo Liu,Yi Zhang,Chuyu Yun,Xian Wang,Huiying Liu,Wen-Bing Yin,Dongyu Zhao,Jing Hang,Shuyang Zhang,Changtao Jiang,Yanli Pang
The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans ( C. albicans ), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans . Mechanistically, formyl-methionine, a metabolite of C. albicans , activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.
研究领域:
微生物学
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心血管疾病
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生物化学
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分子生物学
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PubMed
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Nature Microbiology
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2026
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IF 18.7
Song Yabing,Chen Jinxin,Wan Junhua,Zhang Jiamo,Liu Qizheng,Sun Fei,Zhang Hanlin,Guo Yuru,Chow Eve W. L.,Chen Yali,Yan Ziyu,Wang Jianbin,Chen Kun,Wang Yue,Gao Jiaxin
Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac ( PB ) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309 Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris .
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Science Advances
·
2023
·Vol. 9
·期 20
·
IF 13.6
Gen Wei,Quanyi Liu,Xiaoyu Wang,Zijun Zhou,Xiaozhi Zhao,Wanqing Zhou,Wanling Liu,Yihong Zhang,Shujie Liu,Chenxin Zhu,Hui Wei
Molecular therapeutics are limited for Candida vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS2 nanozymes [reduced graphene oxide (rGO)] with Lactobacillus-produced lactic acid and H2O2, a responsive hyaluronic acid (HA) hydrogel rGO@FeS2/Lactobacillus@HA (FeLab) is developed. FeLab has simultaneous anti–Candida albicans and vaginal microbiota–modulating activities. In particular, the hydroxyl radical produced from rGO@FeS2 nanozymes and Lactobacillus kills C. albicans isolated from clinical specimens without affecting Lactobacillus. In mice with Candida vaginitis, FeLab has obvious anti–C. albicans activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of Firmicutes (especially Lactobacillus) and a decrease in Proteobacteria reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for Candida vaginitis therapy.
研究领域:
药学
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微生物学
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纳米技术
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妇科学
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MICROCHEMICAL JOURNAL
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2023
·
IF 4.8
Yongfa Cheng,Lingzhi Cheong,Yongyong Li,Yongjiang Lou,Shiqian Fu
The high toxicity and bioaccumulation effects of nitroaromatic pesticides and their serious environmental risks have led to a sharp increase in public concern about pesticide residues. Present work developed a direct, rapid, sensitive and reliable Candida rugosa lipase (CRL)@ the ordered macro-microporous ZIF-8 (MAC-ZIF-8) nanofibers biosensor (CRL@MAC-ZIF-8 nanofibers) for methyl parathion and chlornitrofen residues detection in lake water. The biosensors fabricated by the CRL@MAC-ZIF-8 nanofibers demonstrated wide linear range for both methyl parathion (0.5–114 µM) and chlornitrofen (1–40 µM) detection. The biosensors also demonstrated good reusability for methyl parathion detection with retainment of more than 97% of its initial response after scanning continuously for 100 times. During 1 month storage stability test at 4 °C, the fabricated biosensor demonstrated excellent stability for methyl parathion detection with retainment of 86%-100% of its initial response. Meanwhile, the biosensors also demonstrated good recovery rates when the biosensors were used to detect methyl parathion and chlornitrofen residues in lake water sample.
研究领域:
环境科学
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生物传感器技术
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分析化学
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BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2021
·Vol. 45
·期 1
·147-158
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IF 3.21
Jiaojiao Xia,Yan Yan,Bin Zou,Feng Liu
The cross-linked enzyme aggregates (CLEAs) are one of the technologies that quickly immobilize the enzyme without a carrier. In this study, ionic liquid with amino group (1-aminopropyl-3-methylimidazole bromide, FIL) was used as the novel functional surface molecule to modify CRL ( Candida rugosa lipase, CRL). The enzymatic properties of CRL-FIL-CLEAs were investigated. The activity of CRL-FIL-CLEAs (5.51 U/mg protein) was 1.9 times higher than that of CRL-CLEAs (2.86 U/mg protein) without surface modification. After incubating in a centrifuge tube for 50 min at 60 °C, CRL-FIL-CLEAs still maintained 61% of its initial activity, while the value for CRL-CLEAs was only 22%. After repeated use for five times, compared with the 22% residual activity of CRL-CLEAs, the value of CRL-FIL-CLEAs was 51%. Based on the above results, it was indicated that this method provided a new idea for the effective synthesis of immobilized enzyme.
研究领域:
生物化学
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酶工程
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生物催化
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2025
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IF 2.8
Zhen-Yu Zhao,Ya-Ning Che,Qian Huang,Han-Wen Yang,Xian-Hua Wang,Lin-Yi Dong
Candida albicans is the leading cause of invasive fungal disease; candidemia carries 30–40 % mortality. It commonly colonizes human mucosa as a commensal, but immunosuppression or disrupted microbiota enables opportunistic infection. Therefore, rapid, reliable diagnostics are vital to improve public health. In this study, a magnetic solid-phase microextraction (MSPE) technique based on nystatin-functionalized magnetic nanoparticles (Fe₃O₄@NYS) was developed to achieve the dual objectives of efficiently enriching C. albicans rapidly and extracting its deoxyribonucleic acid (DNA). Optimization of capture conditions enabled rapid enrichment of C. albicans with a maximum recovery rate of approximately 90 %. Subsequent to the capture of C. albicans, DNA extraction was performed on the Fe₃O₄@NYS- C. albicans complexes. Notably, Fe₃O₄@NYS facilitated the extraction of a substantial quantity of DNA, with the extraction yield reaching 1200 ng/mg. Therefore, the integration of DNA extraction with quantitative polymerase chain reaction (qPCR) technology enables sensitive and specific detection of C. albicans in real samples. The strategy demonstrated excellent linearity within the concentration range of 4.20 × 10 2 to 4.20 × 10 7 CFU mL −1 for C. albicans . The high sensitivity and accuracy of this method were confirmed in honey samples, showcasing a limit of detection (LOD) 420 CFU mL −1 , recoveries between 98.1 % and 99.8 %, and relative standard deviations (RSD) not exceeding 2.51 %. This method presents an innovative strategy for point-of-care clinical diagnosis, disease surveillance, and biosafety management, demonstrating substantial potential for the efficient isolation of DNA from complex biological matrices.
研究领域:
微生物学
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临床诊断
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纳米技术
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分子生物学
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传染病
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2012
·Vol. 127
·期 6
·4251-4255
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IF 1.289
Wentao Liu,Hongdong Duan,Xia Meng,Dawei Qin,Xingjian Wang,Juan Zhang
A series of macroporous beaded terpolymers with epoxy groups were synthesized by suspension polymerization with glycidyl methacrylate (GMA), ethylene glycol dimethacrylate (EGDMA), and the third monomers including styrene, methyl methacrylate, n -butyl acrylate (BA), butyl methacrylate (BMA), and 2-hydroxyethyl methacrylate for immobilization of Candida lipolytica lipase. The effect of various third monomers on loading and activity recovery of immobilized lipase were studied. Terpolymers with BA as the third monomer were found to give the biggest loading of lipase, and the activity recovery of lipase immobilized on poly(GMA-EGDMA-BA) terpolymers reached 79.0%. As the content of BA (%) increasing, the loading of lipase enhanced, but the activity recovery reached 88.5% for the initial stage and decreased to 46.9% at last. The poly(GMA-EGDMA-BA-10) showed an optimal result in lipase immobilization. Lipase immobilized on poly(GMA-EGDMA-BA-10) carriers had broader pH and higher temperature stability. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
研究领域:
生物化学
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高分子科学
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酶工程
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生物催化
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材料化学
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Virulence
·
2024
·
IF 5.5
Fen Wang,Jinping Zhang,Qian Zhang,Zhangyong Song,Caiyan Xin
Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
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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传染病学
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