Orthologues of the Anaphase-Promoting Complex/Cyclosome Coactivators Cdc20p and Cdh1p Are Important for Mitotic Progression and Morphogenesis in Candida albicans

Chou, Hsin-I; Glory, Amandeep; Bachewich, Catherine

doi:10.1128/ec.00263-10

Cited by 18 publications

(30 citation statements)

References 91 publications

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“…Our screen identified four candidates as regulators of genome stability in C. albicans. Null or conditional deletion mutants have been obtained and studied for three of these genes, CDC20 (43), RAD51 (44), and RAD53 (45), yet the role of these genes in genome integrity was never addressed, except for RAD53, whose deletion increases the frequency of LOH (16). Reports of C. albicans mutants overexpressing the four candidate genes could not be found in the literature.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, the sustained presence of the Cdc20 protein could perturb genome integrity and our observation that overexpression of C. albicans CDC20 favors LOH, especially through chromosome loss when these types of events can occur, is consistent with this hypothesis. Conditional CDC20 deletion mutants of C. albicans have been characterized by Chou et al (43). Their work suggested that, similar to ScCDC20, CaCDC20 was important for the metaphase-to-anaphase transition and mitotic exit.…”

Section: Discussionmentioning

confidence: 99%

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A FACS-Optimized Screen Identifies Regulators of Genome Stability in Candida albicans

et al. 2015

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f Loss of heterozygosity (LOH) plays important roles in genome dynamics, notably, during tumorigenesis. In the fungal pathogen Candida albicans, LOH contributes to the acquisition of antifungal resistance. In order to investigate the mechanisms that regulate LOH in C. albicans, we have established a novel method combining an artificial heterozygous locus harboring the blue fluorescent protein and green fluorescent protein markers and flow cytometry to detect LOH events at the single-cell level. Using this fluorescence-based method, we have confirmed that elevated temperature, treatment with methyl methanesulfonate, and inactivation of the Mec1 DNA damage checkpoint kinase triggered an increase in the frequency of LOH. Taking advantage of this system, we have searched for C. albicans genes whose overexpression triggered an increase in LOH and identified four candidates, some of which are known regulators of genome dynamics with human homologues contributing to cancer progression. Hence, the approach presented here will allow the implementation of new screens to identify genes that are important for genome stability in C. albicans and more generally in eukaryotic cells.N ormally found as a harmless commensal organism, Candida albicans is also a major fungal pathogen of humans and is capable of causing serious and even life-threatening diseases when the immune system of the host is compromised (1). Although C. albicans is found mostly as a diploid organism, haploid and tetraploid forms have been observed in the laboratory and upon the passage of C. albicans in animal models of infection (2-4). The formation of tetraploids results from mating between diploids of opposite mating types that have undergone the so-called whiteopaque phenotypic switch (5). Meiosis is thought to have been lost in C. albicans, and the formation of haploids from diploids or diploids from tetraploids results from concerted chromosome loss (2, 6). The C. albicans genome is highly plastic, undergoing a number of important genome rearrangements, such as loss-ofheterozygosity (LOH) events, aneuploidies, and the formation of isochromosomes (7). In particular, LOH has been shown to occur during commensal carriage (8) and during systemic infection in a mouse model (9) and to contribute to the acquisition of antifungal resistance (10, 11). Stressful conditions such as high temperature, oxidative stress, or azole antifungal treatment trigger an increase in the frequency of LOH, as well as changes in the mechanisms leading to LOH; while azole treatment and temperature cause an increase in LOH due to chromosome loss and reduplication, oxidative stress results in an increase in gene conversion events (12). Yet, little is known about the molecular mechanisms that control LOH in C. albicans, despite the apparent importance of LOH in the biology of this species. Overall, it has been shown that knockout mutations in genes involved in base excision repair, nucleotide excision repair, and mismatch repair had little impact on the frequency of LOH in C. albican...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

A FACS-Optimized Screen Identifies Regulators of Genome Stability in Candida albicans

et al. 2015

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“…CDC20 encodes a protein that is required for the metaphase-to-anaphase transition and mitotic exit during the cell cycle. Depletion of Cdc20 in a mutant strain displaying resulted in highly polarized growth of yeast buds under yeast growth conditions but had no influence on serum-induced hyphal growth [55]. Further studies are required to investigate the association between Cdc20-mediated cell cycle progression and cell invasion.…”

Section: Resultsmentioning

confidence: 99%

Prediction of Phenotype-Associated Genes via a Cellular Network Approach: A Candida albicans Infection Case Study

et al. 2012

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Candida albicans is the most prevalent opportunistic fungal pathogen in humans causing superficial and serious systemic infections. The infection process can be divided into three stages: adhesion, invasion, and host cell damage. To enhance our understanding of these C. albicans infection stages, this study aimed to predict phenotype-associated genes involved during these three infection stages and their roles in C. albicans–host interactions. In light of the principles that proteins that lie closer to one another in a protein interaction network are more likely to have similar functions, and that genes regulated by the same transcription factors tend to have similar functions, a cellular network approach was proposed to predict the phenotype-associated genes in this study. A total of 4, 12, and 3 genes were predicted as adhesion-, invasion-, and damage-associated genes during C. albicans infection, respectively. These predicted genes highlight the facts that cell surface components are critical for cell adhesion, and that morphogenesis is crucial for cell invasion. In addition, they provide targets for further investigations into the mechanisms of the three C. albicans infection stages. These results give insights into the responses elicited in C. albicans during interaction with the host, possibly instrumental in identifying novel therapies to treat C. albicans infection.

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“…4, Supp. 3) could also contribute to the defective phenotypes observed for the ILS1 conditional mutant in both yeast and hyphal forms as described for the lack of mitotic regulators 44 . Moreover, the metabolic activity of the ILS1 biofilm was considerably lower ( P < 0.01) compared to the WT (−/+DOX) and heterozygous biofilms.…”

Section: Discussionmentioning

confidence: 96%

Screening of Candida albicans GRACE library revealed a unique pattern of biofilm formation under repression of the essential gene ILS1

Costa

Omran

Correia-Mesquita

et al. 2019

Sci Rep

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Candida albicans biofilm formation is governed by a regulatory circuit comprising nine transcription factors which control a network of target genes. However, there are still unknown genes contributing to biofilm features. Thus, the GRACE library was screened to identify genes involved in mature biofilm development. Twenty-nine conditional mutants were selected for a second screening revealing three groups of genes: twenty- two conditional mutants were defective for normal growth and unable to form biofilms; six strains, conditionally defective in genes ARC40, ARC35, ORF19.2438, SKP1, ERG6 , and ADE5,7 that are likely essential or involved in general cell processes, grew normally as free-floating cells but produced less biofilm; finally, the conditional strain for a putative essential isoleucyl- tRNA synthetase gene, ILS1 , was unable to grow as yeast-phase cells but was capable of producing a tridimensional biofilm structure in spite of reduced metabolic activity. This unique biofilm still relied on the classical biofilm genes, while it differentially induced groups of genes involved in adhesion, protein synthesis, cell wall organization, and protein folding. Although the conditional mutant repressed genes annotated for morphology and homeostasis processes affecting morphology and metabolism, the dynamic cell growth enabled the formation of a complex biofilm community independent of ILS1 .

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Orthologues of the Anaphase-Promoting Complex/Cyclosome Coactivators Cdc20p and Cdh1p Are Important for Mitotic Progression and Morphogenesis in Candida albicans

Cited by 18 publications

References 91 publications

A FACS-Optimized Screen Identifies Regulators of Genome Stability in Candida albicans

A FACS-Optimized Screen Identifies Regulators of Genome Stability in Candida albicans

Prediction of Phenotype-Associated Genes via a Cellular Network Approach: A Candida albicans Infection Case Study

Screening of Candida albicans GRACE library revealed a unique pattern of biofilm formation under repression of the essential gene ILS1

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