7 results on '"Zeng, Gui-Sheng"'
Search Results
2. Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans.
- Author
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Yang DL, Hu YL, Yin ZX, Zeng GS, Li D, Zhang YQ, Xu ZH, Guan XM, Weng LX, and Wang LH
- Subjects
- Burkholderia cenocepacia chemistry, Candida albicans physiology, Candidiasis drug therapy, Humans, Microbial Sensitivity Tests, Antifungal Agents pharmacology, Candida albicans drug effects, Drug Resistance, Fungal, Fatty Acids, Monounsaturated adverse effects, Fluconazole pharmacology, Triazoles metabolism
- Abstract
Objective: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo., Methods: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR)., Results: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis., Conclusion: The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
3. Protective Effects of cis-2-Dodecenoic Acid in an Experimental Mouse Model of Vaginal Candidiasis.
- Author
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Yang DL, Zhang YQ, Hu YL, Weng LX, Zeng GS, and Wang LH
- Subjects
- Animals, Candida albicans metabolism, Candida albicans pathogenicity, Candida albicans physiology, Candidiasis, Vulvovaginal genetics, Candidiasis, Vulvovaginal immunology, Candidiasis, Vulvovaginal microbiology, Chemokine CCL2 genetics, Chemokine CCL2 immunology, Disease Models, Animal, Female, Fungal Proteins genetics, Fungal Proteins metabolism, Humans, Insulin-Like Growth Factor Binding Protein 3 genetics, Insulin-Like Growth Factor Binding Protein 3 immunology, Mice, Virulence drug effects, Virulence Factors genetics, Virulence Factors metabolism, Candida albicans drug effects, Candidiasis, Vulvovaginal drug therapy, Fatty Acids, Monounsaturated administration & dosage
- Abstract
Objective: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo., Methods: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms., Results: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively., Conclusion: BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
4. Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes.
- Author
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Tapsin S, Sun M, Shen Y, Zhang H, Lim XN, Susanto TT, Yang SL, Zeng GS, Lee J, Lezhava A, Ang EL, Zhang LH, Wang Y, Zhao H, Nagarajan N, and Wan Y
- Subjects
- Aptamers, Nucleotide chemistry, Genome, Bacterial genetics, Genome, Fungal genetics, RNA metabolism, RNA, Bacterial genetics, RNA, Bacterial metabolism, RNA-Binding Proteins metabolism, Aptamers, Nucleotide genetics, Bacillus subtilis genetics, Candida albicans genetics, Flavin Mononucleotide metabolism, Gene Expression Regulation, Bacterial genetics, Gene Expression Regulation, Fungal genetics, Pseudomonas aeruginosa genetics, Saccharomyces cerevisiae genetics
- Abstract
RNAs are well-suited to act as cellular sensors that detect and respond to metabolite changes in the environment, due to their ability to fold into complex structures. Here, we introduce a genome-wide strategy called PARCEL that experimentally identifies RNA aptamers in vitro, in a high-throughput manner. By applying PARCEL to a collection of prokaryotic and eukaryotic organisms, we have revealed 58 new RNA aptamers to three key metabolites, greatly expanding the list of natural RNA aptamers. The newly identified RNA aptamers exhibit significant sequence conservation, are highly structured and show an unexpected prevalence in coding regions. We identified a prokaryotic precursor tmRNA that binds vitamin B2 (FMN) to facilitate its maturation, as well as eukaryotic mRNAs that bind and respond to FMN, suggesting FMN as the second RNA-binding ligand to affect eukaryotic expression. PARCEL results show that RNA-based sensing and gene regulation is more widespread than previously appreciated in different organisms.
- Published
- 2018
- Full Text
- View/download PDF
5. Phosphoregulation of Nap1 plays a role in septin ring dynamics and morphogenesis in Candida albicans.
- Author
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Huang ZX, Zhao P, Zeng GS, Wang YM, Sudbery I, and Wang Y
- Subjects
- Animals, Candida albicans cytology, Candida albicans growth & development, Candidiasis microbiology, Candidiasis pathology, Cell Cycle, Disease Models, Animal, Fungal Proteins chemistry, Fungal Proteins genetics, Fungal Proteins metabolism, Gene Deletion, Mass Spectrometry, Mice, Mice, Inbred BALB C, Mutagenesis, Site-Directed, Nucleosome Assembly Protein 1 chemistry, Nucleosome Assembly Protein 1 genetics, Phosphorylation, Protein Processing, Post-Translational, Virulence, Candida albicans genetics, Candida albicans metabolism, Gene Expression Regulation, Fungal, Macromolecular Substances metabolism, Nucleosome Assembly Protein 1 metabolism, Septins metabolism
- Abstract
Unlabelled: Nap1 has long been identified as a potential septin regulator in yeasts. However, its function and regulation remain poorly defined. Here, we report functional characterization of Nap1 in the human-pathogenic fungus Candida albicans. We find that deletion of NAP1 causes constitutive filamentous growth and changes of septin dynamics. We present evidence that Nap1's cellular localization and function are regulated by phosphorylation. Phos-tag gel electrophoresis revealed that Nap1 phosphorylation is cell cycle dependent, exhibiting the lowest level around the time of bud emergence. Mass spectrometry identified 10 phosphoserine and phosphothreonine residues in a cluster near the N terminus, and mutation of these residues affected Nap1's localization to the septin ring and cellular function. Nap1 phosphorylation involves two septin ring-associated kinases, Cla4 and Gin4, and its dephosphorylation occurs at the septin ring in a manner dependent on the phosphatases PP2A and Cdc14. Furthermore, the nap1Δ/Δ mutant and alleles carrying mutations of the phosphorylation sites exhibited greatly reduced virulence in a mouse model of systemic candidiasis. Together, our findings not only provide new mechanistic insights into Nap1's function and regulation but also suggest the potential to target Nap1 in future therapeutic design., Importance: Septins are conserved filament-forming GTPases involved in a wide range of cellular events, such as cytokinesis, exocytosis, and morphogenesis. In Candida albicans, the most prevalent human fungal pathogen, septin functions are indispensable for its virulence. However, the molecular mechanisms by which septin structures are regulated are poorly understood. In this study, we deleted NAP1, a gene encoding a putative septin regulator, in C. albicans and found that cells lacking NAP1 showed abnormalities in morphology, invasive growth, and septin ring dynamics. We identified a conserved N-terminal phosphorylation cluster on Nap1 and demonstrated that phosphorylation at these sites regulates Nap1 localization and function. Importantly, deletion of NAP1 or mutation in the N-terminal phosphorylation cluster strongly reduced the virulence of C. albicans in a mouse model of systemic infection. Thus, this study not only provides mechanistic insights into septin regulation but also suggests Nap1 as a potential antifungal target.
- Published
- 2014
- Full Text
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6. Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary-phase entry and stress response in Candida albicans.
- Author
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Zhu Y, Fang HM, Wang YM, Zeng GS, Zheng XD, and Wang Y
- Subjects
- Amino Acid Sequence, Antifungal Agents toxicity, Candida albicans drug effects, Candida albicans genetics, Cobalt toxicity, GTP Phosphohydrolases genetics, Gene Deletion, Genetic Complementation Test, Hydrogen Peroxide toxicity, Hyphae growth & development, Microbial Viability, Molecular Sequence Data, Phylogeny, Sequence Alignment, Candida albicans physiology, Cyclic AMP metabolism, Fungal Proteins physiology, GTP Phosphohydrolases physiology, Gene Expression Regulation, Fungal, Stress, Physiological
- Abstract
The GTPase Ras1 activates the yeast-to-hypha transition in Candida albicans by activating cAMP synthesis. Here, we have characterized Ras2. Ras2 belongs to a group of atypical Ras proteins in some fungal species that share poor identity with other Ras GTPases with many variations in conserved motifs thought to be crucial for Ras-associated activities. We find that recombinant Ras2 is enzymatically as active as Ras1. However, only RAS1 can rescue the lethality of the Saccharomyces cerevisiae ras1 ras2 mutant, suggesting functional divergence of the two genes. ras2Delta is normal in hyphal growth, but deleting RAS2 in the ras1Delta background greatly aggravates the hyphal defect, indicating that Ras2 also has a role in hyphal development. Strikingly, while RAS1 deletion causes a approximately 20-fold decrease in cellular cAMP, further deletion of RAS2 restores it to approximately 30% of the wild-type level. Consistently, while the ras1Delta mutant enters the stationary phase prematurely, the double mutant does so normally. Moreover, ras1Delta cells exhibit increased resistance to H(2)O(2) and higher sensitivity to the heavy metal Co(2+), whereas ras2Delta cells show the opposite phenotypes. Together, our data reveal a novel regulatory mechanism by which two antagonizing Ras GTPases balance each other in regulating multiple cellular processes in C. albicans.
- Published
- 2009
- Full Text
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7. 4-Thioxo-3,5-dithia-1,7-hepta-nedioic acid.
- Author
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Zeng GS, Zou JP, Peng Q, Wen ZH, and Zhang AQ
- Abstract
The complete molecule of the title compound, C(5)H(6)O(4)S(3), is generated by crystallographic twofold symmetry with the C=S group lying on the rotation axis. The molecules are linked through weak hydrogen-bond contacts by glide-plane operations to form R(2) (2)(20) rings and ladder-like C(4) chains along the c axis.
- Published
- 2008
- Full Text
- View/download PDF
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