Advanced Science
·
2024
·
IF 14.3
Cheng Zhen,Li Wang,Yanru Feng,Malcolm Whiteway,Sijin Hang,Jinhua Yu,Hui Lu,Yuanying Jiang
Candidiasis, which presents a substantial risk to human well-being, is frequently treated with azoles. However, drug-drug interactions caused by azoles inhibiting the human CYP3A4 enzyme, together with increasing resistance of Candida species to azoles, represent serious issues with this class of drug, making it imperative to develop innovative antifungal drugs to tackle this growing clinical challenge. A drug repurposing approach is used to examine a library of Food and Drug Administration (FDA)-approved drugs, ultimately identifying otilonium bromide (OTB) as an exceptionally encouraging antifungal agent. Mechanistically, OTB impairs vesicle-mediated trafficking by targeting Sec31, thereby impeding the plasma membrane (PM) localization of the ergosterol transporters, such as Sip3. Consequently, OTB obstructs the movement of ergosterol across membranes and triggers cytotoxic autophagy. It is noteworthy that C. albicans encounters challenges in developing resistance to OTB because it is not a substrate for drug transporters. This study opens a new door for antifungal therapy, wherein OTB disrupts ergosterol subcellular distribution and induces cytotoxic autophagy. Additionally, it circumvents the hepatotoxicity associated with azole-mediated liver enzyme inhibition and avoids export-mediated drug resistance in C. albicans .
研究领域:
药理学
·
微生物学
·
分子生物学
·
医学真菌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
·
2021
·Vol. 48
·期 3
·857-865
·
IF 1.73
Ming-Kun Shao,Wen-Jin Qi,Meng-Yao Hou,Dan-Dan Luo
Background The role of fungal pathogenic factors and the immune response of the vaginal epithelium in vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are still unclear. Our study wants to clarify whether there are differences in pathogenic factors between VVC and RVVC strains, confirm the roles of pathogenic factors in the pathogenesis of RVVC, and analyze the influence of pathogenic factors on vaginal host immunity. Methods VVC- and RVVC-causing Candida albicans strains were genotyped with 25S rDNA. Drug susceptibility assays using a modified alamarBlue broth microdilution method were carried out. Milk culture medium and egg yolk culture medium were used to measure the secreted aspartate protease (Sap) and phospholipase (Plb) activity of the samples. We used C. albicans with different Sap activity levels to induce RVVC in mice and measured interleukin 4 (IL4), interleukin 8 (IL8), and interleukin 17 (IL17) in vaginal lavage fluid at different stages of RVVC infection. Results There were no significant differences between VVC and RVVC fungi except that the Sap activity was lower for RVVC-causing C. albicans than for VVC-causing C. albicans . C. albicans with both strong Sap and weak Sap induced RVVC in mice. C. albicans with strong Sap had a reduced RVVC infection rate. In addition, C. albicans with strong Sap stimulated the vaginal epithelium to secrete more IL4, IL8, and IL17. Conclusion Compared with that of VVC-causing C. albicans , the Sap activity of RVVC-causing C. albicans was lower. C. albicans with strong Sap was less capable of causing repeated vaginal infections than that with weak Sap and stimulated the vaginal epithelium to produce more cytokines.
研究领域:
微生物学
·
免疫学
·
传染病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Materials Interfaces
·
2022
·Vol. 9
·期 16
·2102590
·
IF 6.389
Bin Zhou,Guohua Li,Mingxi Wu,Zhangkai Zhou,Xin Cai,Jingxuan Cai,Jianhua Zhou
A platform for real-time monitoring and comprehensively studying the adhesion process of microorganisms onto material surfaces as well as their bioactivity on the surface is very helpful to reveal the microbial contamination mechanism on drainage catheters, intravascular stents, and implanted sensors. Herein, a multifunctional sensor based on localized surface plasmon resonance of gold nano-match head arrays (GNMAs) is developed for monitoring the adhesion behavior of microorganisms (such as Candida albicans , i.e., C. albicans ) as well as its inhibitory activity. The sensor is fabricated through soft lithography processes using nanopatterned polydimethylsiloxane stamps, and modified with polymers of different charges for investigating the adhesion of C. albicans onto different charged surfaces. The spectroscopic study shows that C. albicans are more favorable to positively charged surfaces than negatively charged ones, which is also proven by the fluorescence images under microscope. Moreover, the authors demonstrate that the GNMA modified with poly- l -lysine (PLL) can effectively kill the adhered C. albicans due to the membrane destruction and the reactive oxygen species induced by PLL. These unique advantages suggest that the sensor is capable as both an antifungal study system and a real-time monitoring platform for antifungal performance evaluation.
研究领域:
生物医学工程
·
微生物学
·
纳米技术
·
材料科学
✓ 已验证
DOI
高影响因子
eLife
·
2023
·
IF 7.7
Xun Sun,Jing Yu,Cheng Zhu,Xinreng Mo,Qiangqiang Sun,Dandan Yang,Chang Su,Yang Lu
The GAL pathway of yeasts has long served as a model system for understanding of how regulatory mode of eukaryotic metabolic pathways evolves. While Gal4 mode has been well-characterized in Saccharomycetaceae clade, little is known about the regulation of the GAL pathway in other yeasts. Here, we find that Rep1, a Ndt80-like family transcription factor, serves as a galactose sensor in the commensal-pathogenic fungus Candida albicans. It is presented at the GAL gene promoters independent of the presence of galactose. Rep1 recognizes galactose via a direct physical interaction. The net result of this interaction is the recruitment of a transcriptional activator Cga1 (Candida galactose gene activator, orf19.4959) and transcription of the GAL genes proceeds. Rep1 and Cga1 are conserved across the CTG species. Rep1 itself does not possess transcriptional activity. Instead, it provides a scaffold to recruit different factors for transcriptional regulation. Rep1-Cga1 mode of regulation represents a new example of network rewiring in fungi, which provides insight into how C. albicans evolves transcriptional programs to colonize diverse host niches.
研究领域:
分子生物学
·
微生物学
·
真菌遗传学
·
转录调控
✓ 已验证
DOI
PubMed
高影响因子
Catalysts
·
2026
·Vol. 16
·期 5
·377
·
IF 4.5
Sining Wei,Mahwish Aziz,Yilin Zhang,Jian Xiong,Cheng Cheng,Bin Wu
This study addressed the issue of insufficient activity in CALB lipase during the catalytic synthesis of key chiral intermediates for moxifloxacin. A structure-guided protein engineering strategy was employed to systematically modify its functional domains. Through molecular dynamics simulations of CALB-I189K, multiple regions exhibiting high conformational flexibility were preliminarily identified. Subsequently, by integrating 3D structural alignment with active site pocket distance analysis, the functionally most critical region (143–146) was selected. A site-directed saturation mutation library was constructed specifically targeting this region. Building upon the previously reported CALB-I189K, a mutant I189K/L144R/A146K was ultimately obtained through high-throughput screening combined with chiral HPLC validation. This mutant maintains excellent stereoselectivity (E = 206.52) while enhancing catalytic efficiency (kcat/Κm) to 273.73 min−1·mM−1, approximately 4.5-fold that of I189K. At a substrate concentration of 1 M, it achieves 50% conversion within 2.6 h, demonstrating kinetic resolution capabilities approaching industrial standards. Molecular simulation analysis indicates that the L144R and A146K mutations synergistically enhance catalytic performance primarily by optimizing spatial distances between catalytic residues. This study not only provides a high-performance catalyst for the efficient biosynthesis of moxifloxacin chiral intermediates but also offers new insights for enzyme rational design based on dynamic structural information.
✓ 已验证
DOI
高影响因子
Plasma Processes and Polymers
·
2026
·Vol. 23
·期 8
·e70236
·
IF 3.2
Sihong Ma,Tianyi Song,Pengyu Zhao,Haoqian Chen,Tianshuo Yan,Li Guo,Miaojing Li,Zifeng Wang,Dingxin Liu,Xiaohua Wang,Mingzhe Rong
Mixed infections caused by fungal-bacterial polymicrobial biofilms pose major clinical challenges, and plasma-activated water (PAW) has potential for the treatment of infections. In this study, Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA) were used to establish fungal-bacterial biofilms, and the inactivation effects of PAWs on the two microorganisms in biofilms were evaluated. The 30-min PAW treatment reduced the viable C. albicans and MRSA within biofilms on silica films to below 2.00-log 10 CFU/mL. The two consecutive 30-min PAW treatments achieved significant reductions of approximately 3.32-log 10 CFU/mL for C. albicans and 4.08-log 10 CFU/mL for MRSA in biofilms on wound-mimicking porcine skins. Therefore, owing to its non-selective inactivation ability, PAW provides an alternative therapy for the mixed infections caused by diverse microorganisms.
✓ 已验证
产品关联
DOI
高影响因子
Virulence
·
2025
·
IF 5.4
Guangyuan Yang,Xiaojia Niu,Tian Zhuang,Xiaoxiao Zhu,Qianwen Xu,Hongchen Wang,Jing Shao,Changzhong Wang,Yue Yang,Tianming Wang,Wenfan Wei,Daqiang Wu
The mitochondrial anchoring protein Num1 directly affects mitochondrial redox function, cell division, and growth in unicellular fungi. However, the functional characterization of Num11, its Candida albicans homolog, remains elusive. Our investigation revealed that Num11 deletion in C. albicans caused profound cellular defects: (1) Disrupted cell cycle progression and mitochondrial dysfunction manifesting as mitochondrial morphological aggregation, ATP depletion, membrane potential collapse, and ROS overproduction; (2) Hypersensitivity to cell wall-perturbing agents accompanied by thicker cell walls and increased surface exposure of β-glucan/chitin; (3) Enhanced macrophage phagocytosis and proinflammatory cytokine release. These cellular alterations translated to significantly attenuated virulence in both Galleria mellonella and systematic mice infection models. Mechanistically, transcriptome profiling and protein interaction analyses demonstrated Num11 deficiency hyperactivates the Cdc42-Cek1 MAPK cascade (phospho-Cek1 increased), driving cell wall remodeling. Our findings establish Num11’s dual closely connected regulatory roles in C. albicans pathogenesis: as a mitochondrial scaffold maintaining bioenergetic homeostasis to attenuate growth and as a negative regulator of the Cdc42-Cek1 axis controlling cell wall architecture through affection on mitochondria. These coordinated actions collectively underscore Num11’s critical role in mediating host–pathogen interactions during invasive candidiasis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antibiotics-Basel
·
2023
·Vol. 12
·期 12
·1675
·
IF 4.8
Ting Fang,Juan Xiong,Li Wang,Zhe Feng,Sijin Hang,Jinhua Yu,Wanqian Li,Yanru Feng,Hui Lu,Yuanying Jiang
Candida albicansfilamentation plays a significant role in developing both mucosal and invasive candidiasis, making it a crucial virulence factor. Consequently, exploring and identifying inhibitors that impede fungal hyphal formation presents an intriguing approach toward antifungal strategies. In line with this anti-filamentation strategy, we conducted a comprehensive screening of a library of FDA-approved drugs to identify compounds that possess inhibitory properties against hyphal growth. The compound octenidine dihydrochloride (OCT) exhibits potent inhibition of hyphal growth inC. albicansacross different hyphae-inducing media at concentrations below or equal to 3.125 μM. This remarkable inhibitory effect extends to biofilm formation and the disruption of mature biofilm. The mechanism underlying OCT’s inhibition of hyphal growth is likely attributed to its capacity to impede ergosterol biosynthesis and induce the generation of reactive oxygen species (ROS), compromising the integrity of the cell membrane. Furthermore, it has been observed that OCT demonstrates protective attributes against invasive candidiasis inGalleria mellonellalarvae through its proficient eradication ofC. albicanscolonization in infectedG. mellonellalarvae by impeding hyphal formation. Although additional investigation is required to mitigate the toxicity of OCT in mammals, it possesses considerable promise as a potent filamentation inhibitor against invasive candidiasis.Keywords:octenidine dihydrochloride;anti-filamentation;Candida albicans;ergosterol biosynthesis
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-10
·
IF 4.38
Ma Yinzheng,Wang Yuanxiao,Zhou Xia,Yang Heng,Zhang Huixin,Chen Wenhan,Zhang Haiying,Zhang Yunxia,He Xiaowen
Clausena lansium (Lour.) Skeels seeds have been shown to have diverse beneficial medical value due to their unique active components. This study analysed the composition of essential oils (EOs) of C. lansium seeds and investigated their potential antifungal effects against Candida strains . A total of forty-six components were identified in all samples by gas chromatography-mass spectrometry (GC–MS). The main components were sabinene, β -phellandrene and 4-terpineol. Thirteen EOs of C. lansium seeds were classified into three clusters based on their components. Cluster analysis showed that the difference between the tropics and subtropics was the greatest. These EOs and the three main chemicals showed different antifungal activities against five Candida species ( C. albicans , C. tropicalis , C. glabrata , C. krusei and C. parapsilosis ). The antifungal activity against C. glabrata and C. krusei was higher than that against other Candida strains. EOs of C. lansium seeds displayed noteworthy antifungal activity against both sensitive and fluconazole-resistant strains, with inhibition zone diameters in the range of 9.4–23.4 mm. Comprehensive analysis illustrated the importance of sabinene, β -phellandrene and 4-terpineol to antifungal activity, and there may be some synergistic effects with other components. These results represent the first report about the correlation between the chemical composition of EOs of C. lansium seeds and antifungal activity. Taken together, the results obtained provide scientific evidence for the traditional use of C. lansium seeds waste.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2024
·
IF 9.7
Shuo Zou,Jiena Chen,Yee-Ying Lee,Yong Wang,Zhen Zhang
Partial acylglycerols are valued for their emulsifying and stabilizing properties, yet precise green synthesis remains challenging due to low yield and selectivity. This study aimed to elucidate the “lipase selectivity-substrate structure-product composition” relationship to enhance the yield of targeted partial acylglycerol. The results showed that lipase exhibited a greater selectivity towards fatty acids with shorter chain lengths and higher unsaturation. Hydroxyl donors also affected the esterification process, with the enzyme-acyl complex exhibiting selectivity towards hydroxyl donors as follows: glycerol > monoacylglycerol > diacylglycerol. Substrate ratio significantly influenced enzymatic reactions; a 10:1 ratio favored triacylglycerol formation (>80 %), while a 1:1 ratio produced > 90 % partial acylglycerols. Molecular docking simulations revealed that substrates primarily interacted with lipase through hydrogen bonding and hydrophobic interactions. A comprehensive understanding of lipase selectivity patterns could facilitate the design of more efficient reaction systems, enabling the conversion of basic lipid resources into desired high value-added products.
研究领域:
生物化学
·
生物催化
·
绿色化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Zhuang Li,Yahui Huang,Jie Tu,Wanzhen Yang,Na Liu,Wei Wang,Chunquan Sheng
Over the past several decades, invasive fungal infections, especially candidiasis, have caused dramatic morbidity and mortality due to ineffective antifungal drugs and severe drug resistance. Herein, new BRD4–histone deacetylase (HDAC) inhibitors were designed to restore the susceptibility of Candida albicans (C. albicans) to fluconazole (FLC). Interestingly, several compounds showed excellent selectivity against fungal HDACs. In particular, compound B2 showed excellent synergistic effect with FLC against resistant C. albicans (FICI = 0.063) with high selectivity against fungal HDACs (SI = 1653) and low cytotoxicity. Compound B2 effectively synergized with FLC and prevented biofilm formation and morphological transition in resistant C. albicans, potentiating the antifungal activity of FLC in vivo and significantly reducing kidney fungal loads. Thus, this drug combination is promising in the treatment of resistant C. albicans infections.
研究领域:
微生物学
·
药理学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Fang-Ying Zhu,Jia Zhong,Qi Shen,Dong-Xu Jia,Shi-Jin Ma,Jun Du,Hui Wu,Qing Yang,Min Cao,Zhi-Qiang Liu,Yu-Guo Zheng
d -(+)-pantothenic acid (DPA) has been widely used in feed and food additives and pharmaceutical industries. d -(−)-pantolactone ( D PL) is a key intermediate in the production of DPA . The bio-asymmetric synthesis of D PL from ketopantoyl lactone (KPL) by conjugated polyketone reductases is an attractive route. In this study, high expression of a conjugated polyketone reductase from Candida glabrata ( Cgl CPR) in Escherichia coli was achieved after optimization of vectors. The optimum temperature and pH of purified Cgl CPR were 40 °C and 4.5, respectively. The Michaelis-Menten constant K m and V max of purified Cgl CPR for KPL are 73.09 μM and 2.29 μmol mg −1 s −1 , respectively. To circumvent the spontaneous degradation of KPL in biocatalytic reaction of synthesizing DPL, the reaction was performed by a strategy combing fed-batch addition of whole cell catalyst with substrate semi-continuous feeding. At the final KPL loading of 1000 mM, DPL with an isolated yield of 94.24 % was obtained after 13-h reaction and enantiomeric excess ( e.e. ) achieved > 99 %. The space-time yield of DPL reached to 228 g L −1 d −1 .
研究领域:
生物技术
·
生物化学
·
酶学
·
药学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）