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  • 1
    Online Resource
    Online Resource
    Condition-specific series of metabolic sub-networks and its application for gene set enrichment analysis
    Oxford University Press (OUP) ; 2019
    In:  Bioinformatics Vol. 35, No. 13 ( 2019-07-01), p. 2258-2266
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 35, No. 13 ( 2019-07-01), p. 2258-2266
    Abstract: Genome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism’s metabolism, yet their integration to achieve biological insight remains challenging. Results We investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO. Availability and implementation The metaboGSE R package is available at https://CRAN.R-project.org/package=metaboGSE. Supplementary information Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4803 , 1367-4811
    URL: Article
    DOI: 10.1093/bioinformatics/bty929
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 2
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    RNA Enrichment Method for Quantitative Transcriptional Analysis of Pathogens In Vivo Applied to the Fungus Candida albicans
    American Society for Microbiology ; 2015
    In:  mBio Vol. 6, No. 5 ( 2015-10-30)
    Details
    In: mBio, American Society for Microbiology, Vol. 6, No. 5 ( 2015-10-30)
    Abstract: Understanding the mechanisms utilized by pathogens to infect and cause disease in their hosts is crucial for rational drug development. Transcriptomic studies may help investigations of these mechanisms by determining which genes are expressed specifically during infection. This task has been difficult so far, since the proportion of microbial biomass in infected tissues is often extremely low, thus limiting the depth of sequencing and comprehensive transcriptome analysis. Here, we adapted a technology to capture and enrich C. albicans RNA, which was next used for deep RNA sequencing directly from infected tissues from two different host organisms. The high-resolution transcriptome revealed a large number of genes that were so far unknown to participate in infection, which will likely constitute a focus of study in the future. More importantly, this method may be adapted to perform transcript profiling of any other microbes during host infection or colonization.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.00942-15
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
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  • 3
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    Data_Sheet_7.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Fungal Biology Vol. 2 ( 2021-3-15)
    Details
    In: Frontiers in Fungal Biology, Frontiers Media SA, Vol. 2 ( 2021-3-15)
    Abstract: Candida albicans is a commensal of human mucosae, but also one of the most common fungal pathogens of humans. Systemic infections caused by this fungus, mostly affecting immunocompromised patients, are associated to fatality rates as high as 50% despite the available treatments. In order to improve this situation, it is necessary to fully understand how C. albicans is able to cause disease and how it copes with the host defenses. Our previous studies have revealed the importance of the C. albicans gene MBF1 in virulence and ability to colonize internal organs of mammalian and insect hosts. MBF1 encodes a putative transcriptional regulator, and as such it likely has an impact in the regulation of C. albicans gene expression during host infection. Here, recent advances in RNA-seq technologies were used to obtain a detailed analysis of the impact of MBF1 on C. albicans gene expression both in vitro and during infection. MBF1 was involved in the regulation of several genes with a role in glycolysis and response to stress, particularly to nutritional stress. We also investigated whether an interaction existed between MBF1 and GCN4 , a master regulator of response to starvation, and found that both genes were needed for resistance to amino acid starvation, suggesting some level of interaction between the two. Reinforcing this idea, we showed that the proteins encoded by both genes could interact. Consistent with the role of MBF1 in virulence, we also established that GCN4 was necessary for virulence in the mouse model of systemic infection as well as in the Galleria mellonella infection model.
    Type of Medium: Online Resource
    ISSN: 2673-6128
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/ffunb.2021.658899
    DOI: 10.3389/ffunb.2021.658899.s001
    DOI: 10.3389/ffunb.2021.658899.s002
    DOI: 10.3389/ffunb.2021.658899.s003
    DOI: 10.3389/ffunb.2021.658899.s004
    DOI: 10.3389/ffunb.2021.658899.s005
    DOI: 10.3389/ffunb.2021.658899.s006
    DOI: 10.3389/ffunb.2021.658899.s007
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 4
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    Evaluation of sixteen ELISA SARS-CoV-2 serological tests
    Elsevier BV ; 2021
    In:  Journal of Clinical Virology Vol. 142 ( 2021-09), p. 104931-
    Details
    In: Journal of Clinical Virology, Elsevier BV, Vol. 142 ( 2021-09), p. 104931-
    Type of Medium: Online Resource
    ISSN: 1386-6532
    URL: Article
    DOI: 10.1016/j.jcv.2021.104931
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 5
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    The CRH Family Coding for Cell Wall Glycosylphosphatidylinositol Proteins with a Predicted Transglycosidase Domain Affects Cell Wall Organization and Virulence of Candida albicans
    Elsevier BV ; 2006
    In:  Journal of Biological Chemistry Vol. 281, No. 52 ( 2006-12), p. 40399-40411
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 281, No. 52 ( 2006-12), p. 40399-40411
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M606361200
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
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  • 6
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    Azole resistance in a Candida albicans mutant lacking the ABC transporter CDR6/ROA1 depends on TOR signaling
    Elsevier BV ; 2018
    In:  Journal of Biological Chemistry Vol. 293, No. 2 ( 2018-01), p. 412-432
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 293, No. 2 ( 2018-01), p. 412-432
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M117.807032
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2997-X
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  • 7
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    Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies
    American Society for Microbiology ; 2021
    In:  Journal of Virology Vol. 95, No. 3 ( 2021-01-13)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 95, No. 3 ( 2021-01-13)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses to the spike (S) protein monomer, S protein native trimeric form, or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection ( n  = 93) and in individuals enrolled in a postinfection seroprevalence population study ( n  = 578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein, or within a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute-infection-phase samples. Interestingly, compared to anti-S antibody responses, those against the N protein appear to wane in the postinfection cohort. Seroprevalence in a “positive patient contacts” group ( n  = 177) was underestimated by N protein assays by 10.9 to 32.2%, while the “randomly selected” general population group ( n  = 311) was reduced by up to 45% relative to the S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies. IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and postinfection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection, but that responses against N appear to wane in the postinfection phase where those against the S protein persist over time. The most sensitive serological assay in both acute and postinfection phases used the native S protein trimer as the binding antigen, which has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01828-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
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    detail.hit.zdb_id: 80174-4
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  • 8
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    Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms
    American Society for Microbiology ; 2016
    In:  Antimicrobial Agents and Chemotherapy Vol. 60, No. 1 ( 2016-01), p. 229-238
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 1 ( 2016-01), p. 229-238
    Abstract: Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole, itraconazole, posaconazole, and voriconazole. Saccharomyces cerevisiae expressing the Candida albicans and C. glabrata ATP binding cassette (ABC) transporters ( CDR1 , CDR2 , and CgCDR1 ), major facilitator ( MDR1 ), and lanosterol 14-α-sterol-demethylase ( ERG11 ) alleles with mutations were used. In addition, pairs of C. albicans and C. glabrata strains from matched clinical isolates with known azole resistance mechanisms were investigated. The expression of ABC transporters increased all azole MICs, suggesting that all azoles tested were substrates of ABC transporters. The expression of MDR1 did not increase posaconazole, itraconazole, and isavuconazole MICs. Relative increases of azole MICs (from 4- to 32-fold) were observed for fluconazole, voriconazole, and isavuconazole when at least two mutations were present in the same ERG11 allele. Upon MIC testing of azoles with clinical C. albicans and C. glabrata isolates with known resistance mechanisms, the MIC 90 s of C. albicans for fluconazole, voriconazole, itraconazole, posaconazole, and isavuconazole were 128, 2, 1, 0.5, and 2 μg/ml, respectively, while in C. glabrata they were 128, 2, 4, 4, and 16 μg/ml, respectively. In conclusion, the effects of azole resistance mechanisms on isavuconazole did not differ significantly from those of other azoles. Resistance mechanisms in yeasts involving ABC transporters and ERG11 decreased the activity of isavuconazole, while MDR1 had limited effect.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02157-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
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  • 9
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    TAC1 , Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2
    American Society for Microbiology ; 2004
    In:  Eukaryotic Cell Vol. 3, No. 6 ( 2004-12), p. 1639-1652
    Details
    In: Eukaryotic Cell, American Society for Microbiology, Vol. 3, No. 6 ( 2004-12), p. 1639-1652
    Abstract: The ABC transporter genes CDR1 and CDR2 can be upregulated in Candida albicans developing resistance to azoles or can be upregulated by exposing cells transiently to drugs such as fluphenazine. The cis -acting drug-responsive element (DRE) present in the promoters of both genes and necessary for their upregulation contains 5′-CGG-3′ triplets that are often recognized by transcriptional activators with Zn(2)-Cys(6) fingers. In order to isolate regulators of CDR1 and CDR2 , the C. albicans genome was searched for genes encoding proteins with Zn(2)-Cys(6) fingers. Interestingly, three of these genes were tandemly arranged near the mating locus. Their involvement in CDR1 and CDR2 upregulation was addressed because a previous study demonstrated a link between mating locus homozygosity and azole resistance. The deletion of only one of these genes (orf19.3188) was sufficient to result in a loss of transient CDR1 and CDR2 upregulation by fluphenazine and was therefore named TAC1 (transcriptional activator of CDR genes). Tac1p has a nuclear localization, and a fusion of Tac1p with glutathione S -transferase could bind the cis -acting regulatory DRE in both the CDR1 and the CDR2 promoters. TAC1 is also relevant for azole resistance, since a TAC1 allele ( TAC1-2 ) recovered from an azole-resistant strain could trigger constitutive upregulation of CDR1 and CDR2 in an azole-susceptible laboratory strain. Transcript profiling experiments performed with a TAC1 mutant and a revertant containing TAC1-2 revealed not only CDR1 and CDR2 as targets of TAC1 regulation but also other genes ( RTA3 , IFU5 , and HSP12 ) that interestingly contained a DRE-like element in their promoters. In conclusion, TAC1 appears to be the first C. albicans transcription factor involved in the control of genes mediating antifungal resistance.
    Type of Medium: Online Resource
    ISSN: 1535-9778 , 1535-9786
    URL: Article
    DOI: 10.1128/EC.3.6.1639-1652.2004
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
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  • 10
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    Functional Analysis of cis - and trans -Acting Elements of the Candida albicans CDR2 Promoter with a Novel Promoter Reporter System
    American Society for Microbiology ; 2009
    In:  Eukaryotic Cell Vol. 8, No. 8 ( 2009-08), p. 1250-1267
    Details
    In: Eukaryotic Cell, American Society for Microbiology, Vol. 8, No. 8 ( 2009-08), p. 1250-1267
    Abstract: Azole resistance in Candida albicans can be mediated by the upregulation of the ATP binding cassette transporter genes CDR1 and CDR2 . Both genes are regulated by a cis -acting element called the drug-responsive element (DRE), with the consensus sequence 5′-CGGAWATCGGATATTTTTTT-3′, and the transcription factor Tac1p. In order to analyze in detail the DRE sequence necessary for the regulation of CDR1 and CDR2 and properties of TAC1 alleles, a one-hybrid system was designed. This system is based on a P (CDR2) -HIS3 reporter system in which complementation of histidine auxotrophy can be monitored by activation of the reporter system by CDR2 -inducing drugs such as estradiol. Our results show that most of the modifications within the DRE, but especially at the level of CGG triplets, strongly reduce CDR2 expression. The CDR2 DRE was replaced by putative DREs deduced from promoters of coregulated genes ( CDR1 , RTA3 , and IFU5 ). Surprisingly, even if Tac1p was able to bind these putative DREs, as shown by chromatin immunoprecipitation, those from RTA3 and IFU5 did not functionally replace the CDR2 DRE. The one-hybrid system was also used for the identification of gain-of-function (GOF) mutations either in TAC1 alleles from clinical C. albicans isolates or inserted in TAC1 wild-type alleles by random mutagenesis. In all, 17 different GOF mutations were identified at 13 distinct positions. Five of them (G980E, N972D, A736V, T225A, and N977D) have already been described in clinical isolates, and four others (G980W, A736T, N972S, and N972I) occurred at already-described positions, thus suggesting that GOF mutations can occur in a limited number of positions in Tac1p. In conclusion, the one-hybrid system developed here is rapid and powerful and can be used for characterization of cis - and trans -acting elements in C. albicans .
    Type of Medium: Online Resource
    ISSN: 1535-9778 , 1535-9786
    URL: Article
    DOI: 10.1128/EC.00069-09
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2009
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    detail.hit.zdb_id: 2077635-4
    SSG: 12
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