Abstract:
:The transcriptional regulator Pdr1 plays a positive role in regulating azole drug resistance in Candida glabrata. Previous studies have shown the importance of the carboxyl (C)-terminal sequence of Pdr1 in fulfilling its function, as this region mediates interactions between Pdr1 and the co-activator Gal11A and is crucial for activation of Pdr1 targets. However, mechanisms of how Pdr1 is regulated, especially implication of its C-terminus in the regulatory activity, remain uncharacterized. In this study, we unexpectedly observed that the C-terminal modification of Pdr1 in an azole-resistant clinical isolate harboring a single GOF mutation, resulted in adverse effects such as decreased expression levels of Pdr1, downregulation of Pdr1 targets and azole hypersensitivity. Importantly, the C-terminal 3 × FLAG tagging significantly decreased the binding of Pdr1 to the pleiotropic drug response elements in its own promoter, promoted an irregular cellular mislocalization and thereby disrupted the transcriptional autoregulation of this master regulator. Unexpectedly, the aberrant cytoplasmic localization caused a non-functional interaction with Gal11A, a co-activator involved in drug resistance. Based on these findings, we proposed that C-terminal sequence of Pdr1 is vital for its stability and functionality, and targeting regulation of this region may represent a promising future strategy for combating C. glabrata infection and drug resistance.
journal_name
FEMS Yeast Resjournal_title
FEMS yeast researchauthors
Tian Y,Gao N,Ni Q,Mao Y,Dong D,Huang X,Jiang C,Li Z,Zhang L,Wang X,Peng Y,Chen Cdoi
10.1093/femsyr/foy038subject
Has Abstractpub_date
2018-06-01 00:00:00issue
4eissn
1567-1356issn
1567-1364pii
4966987journal_volume
18pub_type
杂志文章abstract::The pathogenic fungus Candida glabrata is relatively resistant to azole antifungals, which target lanosterol 14α-demethylase (Erg11p) in the ergosterol biosynthesis pathway. Our study revealed that C. glabrata exhibits increased azole susceptibility under low-iron conditions. To investigate the molecular basis of this...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12043
更新日期:2013-06-01 00:00:00
abstract::We studied the effect of the loss of the Ser-Thr protein phosphatase Sit4, an important post-translational regulator, on the steady-state levels of the low-affinity glucose transporter Hxt1p and observed a delay in its appearance after high glucose induction, slow growth, and diminished glucose consumption. By analyzi...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2012.00839.x
更新日期:2012-12-01 00:00:00
abstract::Formic acid disrupts mitochondrial electron transport and sequentially causes cell death in mammalian ocular cells by an unidentified molecular mechanism. Here, we show that a low concentration of formic acid induces apoptosis-like cell death in the budding yeast Saccharomyces cerevisiae, with several morphological an...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2008.00375.x
更新日期:2008-06-01 00:00:00
abstract::The transcriptional response of laboratory strains of Saccharomyces cerevisiae to salt or sorbitol stress has been well studied. These studies have yielded valuable data on how the yeast adapts to these stress conditions. However, S. cerevisiae is a saccharophilic fungus and in its natural environment this yeast encou...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/S1567-1356(02)00203-9
更新日期:2003-06-01 00:00:00
abstract::Aldose-1-epimerase or mutarotase (EC 5.1.3.3) catalyzes interconversion of alpha/beta-anomers of aldoses, such as glucose and galactose, and is distributed in a wide variety of organisms from bacteria to humans. Nevertheless, the physiological role of this enzyme has been elusive in most cases, because the alpha-form ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2009.00517.x
更新日期:2009-08-01 00:00:00
abstract::Zinc is a crucial mineral for all organisms as it is an essential cofactor for the proper function of a plethora of proteins and depletion of zinc causes oxidative stress. Glutathione is the major redox buffering agent in the cell and therefore important for mitigation of the adverse effects of oxidative stress. In ma...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fox028
更新日期:2017-06-01 00:00:00
abstract::Heat shock response (HSR) is an important element of cellular homeostasis. In yeast, HSR comprises of the heat shock proteins (Hsps) and the osmolytes trehalose and glycerol. The respective roles of trehalose and Hsp104 in regulating protein aggregation remain ambiguous. We report that trehalose and Hsp104 are importa...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/foy058
更新日期:2018-09-01 00:00:00
abstract::Among existing fungal pathogens, Candida glabrata is outstanding in its capacity to rapidly develop resistance to currently used antifungal agents. Resistance to the class of azoles, which are still widely used agents, varies in proportion (from 5 to 20%) depending on geographical area. Moreover, resistance to the cla...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1093/femsyr/fov025
更新日期:2015-06-01 00:00:00
abstract::Genes of the post-squalene ergosterol biosynthetic pathway in Saccharomyces cerevisiae have been overexpressed in a systematic approach with the aim to construct yeast strains that produce high amounts of sterols from a squalene-accumulating strain. This strain had previously been deregulated by overexpressing a trunc...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/S1567-1356(03)00126-0
更新日期:2003-10-01 00:00:00
abstract::Killer-toxin complexes produced by Kluyveromyces lactis and Pichia acaciae inhibit cell proliferation of Saccharomyces cerevisiae. Analysis of their actions in haploid MATalpha cells revealed that introduction of the opposite mating-type locus (MATa) significantly suppressed antizymosis. Together with resistance expre...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2005.00006.x
更新日期:2006-05-01 00:00:00
abstract::Extracellular proteins of Cryptococcus neoformans are involved in the pathogenesis of cryptococcosis, and some are immunoreactive antigens that may potentially serve as candidates for vaccine development. To further study the extracellular proteome of the human fungal pathogen Cry. neoformans, we conducted a proteomic...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2006.00198.x
更新日期:2007-06-01 00:00:00
abstract::An astaxanthin-overproducing (∼1000 μg g(-1)) strain of Phaffia rhodozyma, termed MK19, was established through 1-methyl-3-nitro-1-nitrosoguanidine and Co60 mutagenesis from wild-type JCM9042 (merely 35-67 μg g(-1)). The total fatty acid content of MK19 was much lower than that of the wild type. Possible causes of the...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2010.00705.x
更新日期:2011-03-01 00:00:00
abstract::Saccharomyces cerevisiae is an excellent ethanol producer, but is rather sensitive to high concentration of ethanol. Here, influences of ethanol on cellular membrane integrity and carbon metabolism of S. cerevisiae were investigated to rationalize mechanism involved in ethanol toxicity. Addition of 5% (v/v) ethanol di...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2012.00818.x
更新日期:2012-09-01 00:00:00
abstract::An extended definition of the term metabolic engineering is given and its successful use in the construction of biorecognition elements of sensors is demonstrated. It is shown that genetic and chemical modifications of methylotrophic yeast cells provide directed changes in their physiological responses towards methano...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/S1567-1356(02)00124-1
更新日期:2002-08-01 00:00:00
abstract::This study addresses the question of whether observable changes in fluxes in the primary carbon metabolism of Saccharomyces cerevisiae occur between the different phases of the cell division cycle. To detect such changes by metabolic flux analysis, a 13C-labeling experiment was performed with a fed-batch culture inocu...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2006.00199.x
更新日期:2007-06-01 00:00:00
abstract::Fourteen indigenous Saccharomyces cerevisiae strains isolated from the barks of three tree species located in the Atlantic Rain Forest and Cerrado biomes in Brazil were genetically and physiologically compared to laboratory strains and to strains from the Brazilian fuel ethanol industry. Although no clear correlation ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fow076
更新日期:2016-11-01 00:00:00
abstract::Cdc37p, the p50 homolog of Saccharomyces cerevisiae, is an Hsp90 cochaperone involved in the targeting of protein kinases to Hsp90. Here we report a role for Cdc37p in osmoadaptive signalling in this yeast. The osmosensitive phenotype that is displayed by the cdc37-34 mutant strain appears not to be the consequence of...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2007.00237.x
更新日期:2007-09-01 00:00:00
abstract::Homologous recombination (HR) is an error-free DNA repair mechanism that maintains genome integrity by repairing double-strand breaks (DSBs). Defects in HR lead to genomic instability and are associated with cancer predisposition. A key step in HR is the formation of Rad51 nucleoprotein filaments which are responsible...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fow073
更新日期:2016-09-01 00:00:00
abstract::Candida albicans maintains genetic diversity by random chromosome alterations, and this diversity allows utilization of various nutrients. Although the alterations seem to occur spontaneously, their frequencies clearly depend on environmental factors. In addition, this microorganism survives in adverse environments, w...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1111/j.1567-1364.2006.00150.x
更新日期:2007-01-01 00:00:00
abstract::Eight yeast strains that asexually reproduce by cell fission were isolated from bee bread of different solitary bees in Germany. DNA sequence analysis revealed that the strains shared the same sequence in the D1/D2 domain of the nuclear large subunit (LSU) rRNA gene with a strain that was previously isolated from a fi...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/foz038
更新日期:2019-06-01 00:00:00
abstract::In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral respon...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fou001
更新日期:2015-03-01 00:00:00
abstract::High initial cell density is used to increase volumetric productivity and shorten production time in lignocellulosic hydrolysate fermentation. Comparison of physiological parameters in high initial cell density cultivation of Saccharomyces cerevisiae in the presence of acetic, formic, levulinic and cinnamic acids demo...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fow072
更新日期:2016-11-01 00:00:00
abstract::In Saccharomyces cerevisiae, the cell integrity pathway plays a role in the oxidative stress response. In this study, we show that the Pkc1 protein mediates oxidative signalling by helping to downregulate ribosomal gene expression when cells are exposed to hydrogen peroxide. An active actin cytoskeleton is required fo...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2011.00754.x
更新日期:2011-12-01 00:00:00
abstract::Viruses are found in almost all organisms and physical habitats. One interesting example is the yeast viral 'killer system'. The virus provides the host with a toxin directed against strains that do not carry it, while the yeast cell enables its propagation. Although yeast viruses are believed to be common, they have ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12086
更新日期:2013-12-01 00:00:00
abstract::Candida albicans is an important opportunistic yeast pathogen of humans and has the ability to form drug-resistant biofilms, with increased expression of multidrug ATP-binding cassette (ABC) transporters. These biofilms are also capable of secreting immune-modulating prostaglandin E2 (PGE2 ) from host-derived arachido...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12093
更新日期:2013-12-01 00:00:00
abstract::Screening for genes affecting super-secreting phenotype of the over-secreting mutant of Kluyveromyces lactis resulted in isolation of the gene named KlMNN10, sharing high homology with Saccharomyces cerevisiae MNN10. The disruption of the KlMNN10 in Kluyveromyces lactis, as well as of MNN10 and MNN11 in Saccharomyces ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/j.femsyr.2004.03.001
更新日期:2004-09-01 00:00:00
abstract::A genetic and cell-biological analysis is provided for Saccharomyces cerevisiae DML1 (YMR211w) encoding a Drosophila melanogaster Misato-like protein. Misato and Dml1p are descendants of an ancestral tubulin-like protein, and exhibit regions with similarity to members of a GTPase family that include eukaryotic tubulin...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/s1567-1356(02)00083-1
更新日期:2002-05-01 00:00:00
abstract::Analysis of nucleotide sequences from the domains 1 and 2 of the large-subunit rDNA demonstrated species of the Pichia fluxuum clade to be phylogenetically isolated, and domains 1 and 2 and internal transcribed spacer rDNA sequence analyses of strains phenotypically identified as P. fluxuum resulted in the discovery o...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2005.00019.x
更新日期:2006-03-01 00:00:00
abstract::Yarrowia lipolytica is a dimorphic fungus whose morphology is controlled by several factors such as pH and different compounds. To determine if the STE11-mitogen-activated protein kinase (MAPK) pathway plays a role in dimorphism of Y. lipolytica, we isolated the gene encoding a Mapkkk. The isolated gene (STE11) has an...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2006.00084.x
更新日期:2006-08-01 00:00:00
abstract::In yeast, rRNA genes can be detected with the FISH technique using rRNA gene probes. This technique yields reliable, reproducible and precise results, but is time-consuming. Here, the primed in situ DNA synthesis (PRINS) procedure has been optimized for rapid detection of yeast rRNA genes. PRINS, which is as sensitive...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2009.00499.x
更新日期:2009-06-01 00:00:00