The diploid genome sequence of
            <i>Candida albicans</i>

Jones, Ted; Federspiel, Nancy A.; Chibana, Hiroji; Dungan, Jan; Kalman, Sumner M.; Magee, B. B.; Newport, George; Thorstenson, Yvonne R.; Agabian, Nina; Magee, Patrick; Davis, Ronald W.; Scherer, Stewart

doi:10.1073/pnas.0401648101

Cited by 698 publications

(580 citation statements)

References 25 publications

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“…The TSA1 gene is present in C. albicans, C. glabrata, C. tropicalis, and C. dubliniensis and is similar to the TSA1 and TSA2 of S. cerevisiae. AHP 11, AHP 12, and AHP 13 are genes from strain SC5314 of C. albicans and show similarity to the S. cerevisiae alkyl hydroperoxide reductase AHP1 (YLR109W) 59 .…”

Section: Acknowledgmentsmentioning

confidence: 99%

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Abegg

Alabarse

Schüller

et al. 2012

Rev. Soc. Bras. Med. Trop.

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Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis account for approximately 95% of identifiable Candida infections. Other species, including C. krusei, C. lusitaniae, and C. guilliermondii, account for less than 5% of cases of invasive candidiasis. The most common causative agent is still C. albicans, but its incidence is declining and the frequencies of other species are increasing. Recently, Furlaneto et al. 1 noted that non-albicans Candida was the predominant species in different clinical specimens, with the exception of urine samples, in a Brazilian tertiary-care hospital. Invasive candidiasis has a mortality rate that approaches 40% 2,3 . Although most people are colonized by Candida sp., the majority never develop invasive candidiasis. Alterations in host immunity, physiological features, or normal microflora, rather than the acquisition of novel or hypervirulent factors by Candida, are suggested to degenerate the commensal-host interaction and lead to an opportunistic infection 4 .During the course of a systemic infection, Candida cells are engulfed by host phagocytes, where they are exposed to reactive oxygen species (ROS) 5 . ROS contribute to the killing of C. albicans in both cultured cells and entire organisms [6][7][8][9] . Upon incubation with macrophages, C. albicans deoxyribonucleic acid (DNA) repair genes are transcriptionally induced, suggesting that DNA damage indeed occurs in the phagosome and that genotoxic hypersensitivity stress would be disadvantageous to the pathogen 10 . Recently, it was demonstrated that a large proportion of C. albicans cell surface antigens related to acute candidemia are involved in oxidative stress 4 . In C. albicans, hyphal cells ABSTRACT Introduction: The capacity to overcome the oxidative stress imposed by phagocytes seems to be critical for Candida species to cause invasive candidiasis. Methods: To better characterize the oxidative stress response (OSR) of 8 clinically relevant Candida sp., glutathione, a vital component of the intracellular redox balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB)-glutathione disulfide (GSSG) reductase reconversion method; the total antioxidant capacity (TAC) was measured using a modified method based on the decolorization of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid radical cation (ABTS* + ). Both methods were used with cellular Candida sp. extracts treated or not with hydrogen peroxide (0.5 mM). Results: Oxidative stress induced by hydrogen peroxide clearly reduced intracellular glutathione levels. This depletion was stronger in Candida albicans and the levels of glutathione in untreated cells were also higher in this species. The TAC demonstrated intra-specific variation. Conclusions: Glutathione levels did not correlate with the measured TAC values, despite this being the most important non-enzymatic intracellular antioxidant molecule. The results indicate that the isolated measurement of TAC does not give a clear picture of the ability of a given Candida sp. to resp...

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Section: Acknowledgmentsmentioning

confidence: 99%

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Abegg

Alabarse

Schüller

et al. 2012

Rev. Soc. Bras. Med. Trop.

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“…phenotypic defects associated with heterozygous deletion strains) and conditional haploinsufficiency, in particular, provide the genetic basis to identify genes whose dosages become susceptible to a defined condition and, thus, are functionally involved in the relevant biological processes. As the genome of C. albicans has been determined and annotated (5,6), a reverse genetic approach can be used to explore haploinsufficiency at the genome level. The resulting assay, the C. albicans fitness test (CaFT) 2 , adapted from an analogous strategy first developed in S. cerevisiae (7,8), consists of ϳ2900 heterozygous deletion strains (ϳ45% genome coverage) in a single pool that can be screened for phenotypic variations in parallel.…”

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confidence: 99%

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

Sillaots

Davison

et al. 2009

Journal of Biological Chemistry

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The balance between saturated and unsaturated fatty acids plays a crucial role in determining the membrane fluidity. In the diploid fungal pathogen Candida albicans, the gene for fatty acid ⌬9 desaturase, OLE1, is essential for viability. Using a reverse genetic approach, termed the fitness test, we identified a group of structurally related synthetic compounds that induce specific hypersensitivity of the OLE1

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“…The genome of C. albicans strain SC5314 was recently sequenced using a whole-genome shotgun approach (Jones et al 2004). A community-based effort involving multiple laboratories subsequently produced a hand-curated annotation of C. albicans coding sequences (Braun et al 2005).…”

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confidence: 99%

Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans

Mitrovich

Tuch²,

Guthrie³

et al. 2007

Genome Res.

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Candida albicans is the most common fungal pathogen of humans. Frequently found as a commensal within the digestive tracts of healthy individuals, C. albicans is an opportunistic pathogen that causes a wide variety of clinical syndromes in immuno-compromised individuals. A comprehensive annotation of the C. albicans genome sequence was recently published. Because many C. albicans coding sequences are interrupted by introns, proper intron annotation is essential for the accurate definition of genes in this pathogen. Intron annotation is also important for identifying potential targets of splicing regulation, a common mechanism of gene control in eukaryotes. In this study, we report an improved annotation of C. albicans introns. In addition to correcting the existing intron annotations, 25% of which were incorrect, we have used novel computational and experimental approaches to identify new introns, bringing the total to 415, almost double the number previously known. Our identification methods focus primarily on intron features rather than protein-coding features, overcoming biases of traditional intron annotation methods. Introns are not randomly distributed in C. albicans, and are over-represented in genes involved in specific cellular processes, such as splicing, translation, and mitochondrial respiration. This nonrandom distribution suggests functional roles for these introns, and we demonstrate that splicing of two transcripts whose introns have unusual sequence features is responsive to environmental factors.[Supplemental material is available online at www.genome.org. The microarray data from this study are available at ArrayExpress (http://www.ebi.ac.uk), accession no. E-MEXP-1003.]The yeast Candida albicans commonly inhabits the mucous membranes and digestive tracts of healthy individuals. Perturbation of a host's immune defenses, however, can cause a dramatic shift to invasive, pathogenic growth. Particularly susceptible are those receiving immunosuppressive therapies, such as cancer and transplant patients (Kullberg and Filler 2002), and individuals infected with HIV, more than 90% of whom will at some point suffer candidiasis (Fidel 2002). C. albicans exhibits remarkable adaptability, capable of successfully invading virtually every human organ and tissue (for review, see Odds 1988). During infection, C. albicans is most commonly associated with mucosal surfaces, but in its most devastating form-disseminated candidiasis-it spreads through the host bloodstream and invades multiple tissues, with an associated mortality in excess of 40% (for example, see Alonso-Valle et al. 2003).Eukaryotic genes are often interrupted by introns, which must be spliced out of gene transcripts for coding sequences to be fully expressed. The regulation of intron splicing can also play an important role in controlling gene expression (for reviews, see only 5% of genes in S. cerevisiae contain introns, and most of these genes contain only one (Davis et al. 2000). The loss of introns within the S. cerevisiae lineage has not be...

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The diploid genome sequence of Candida albicans

Cited by 698 publications

References 25 publications

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans

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