Different levels of DNA methylation in yeast and mycelial forms of Candida albicans

Russell, Peter; Welsch, Jo Anne; Rachlin, Elliot M.; McCloskey, James A.

doi:10.1128/jb.169.9.4393-4395.1987

Cited by 43 publications

(25 citation statements)

References 13 publications

(2 reference statements)

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“…In contrast, mammalian DNAs, such as human and mouse DNAs, in which most of the CpG sequences are methylated, cannot stimulate these cells (data not shown). Certain fungi are known to have unmethylated CpG motifs in their genomes, and this is true for C. albicans (37). Thus, to investigate the involvement of unmethylated CpG motifs in the activity of C. albicans DNA, we stimulated BM-DCs with C. albicans DNA pretreated with DNA methylase and measured the IL-12p40 levels in the culture supernatants.…”

Section: Resultsmentioning

confidence: 99%

Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids fromCandida albicans

et al. 2009

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The innate immune system of humans recognizes the human pathogenic fungus Candida albicans via sugar polymers present in the cell wall, such as mannan and ␤-glucan. Here, we examined whether nucleic acids from C. albicans activate dendritic cells. C. albicans DNA induced interleukin-12p40 (IL-12p40) production and CD40 expression by murine bone marrow-derived myeloid dendritic cells (BM-DCs) in a dose-dependent manner. BM-DCs that lacked Toll-like receptor 4 (TLR4), TLR2, and dectin-1, which are pattern recognition receptors for fungal cell wall components, produced IL-12p40 at levels comparable to the levels produced by BM-DCs from wild-type mice, and DNA from a C. albicans pmr1⌬ null mutant, which has a gross defect in mannosylation, retained the ability to activate BM-DCs. This stimulatory effect disappeared completely after DNase treatment. In contrast, RNase treatment increased production of the cytokine. A similar reduction in cytokine production was observed when BM-DCs from TLR9 ؊/؊ and MyD88 ؊/؊ mice were used. In a luciferase reporter assay, NF-B activation was detected in TLR9-expressing HEK293T cells stimulated with C. albicans DNA. Confocal microscopic analysis showed similar localization of C. albicans DNA and CpG-oligodeoxynucleotide (CpG-ODN) in BM-DCs. Treatment of C. albicans DNA with methylase did not affect its ability to induce IL-12p40 synthesis, whereas the same treatment completely eliminated the ability of CpG-ODN to induce IL-12p40 synthesis. Finally, impaired clearance of this fungal pathogen was not found in the kidneys of TLR9 ؊/؊ mice. These results suggested that C. albicans DNA activated BM-DCs through a TLR9-mediated signaling pathway using a mechanism independent of the unmethylated CpG motif.

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Section: Resultsmentioning

confidence: 99%

Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids fromCandida albicans

et al. 2009

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“…DNA repeats, particularly tandem duplications, are subject to methylation and gene silencing in some fungi, a phenomenon known as RIP, repeat induced point mutation, in Neurospora crassa, and MIP, methylation induced premeiotically, in Ascobolus immersus (Selker, 1997). DNA methylation has been reported to occur in C. albicans and to vary with morphological form (Russel et al, 1987). DNA methylation in N. crassa is inhibited by 5-azacytidine and by trichostatin A, a histone deacetylase inhibitor (Selker, 1998), but both compounds inhibited filamentation of C. albicans, precluding assessment of the effect of methylation on URA3 expression (unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans

et al. 2005

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HWP1 encodes an adhesin of Candida albicans and has been implicated in filamentation and virulence. URA3, an often-used transformation selection marker, is apparently incorrectly expressed when integrated at the HWP1 locus, which results in an attenuated virulence phenotype. Expression of URA3 is compromised by ectopic integration at other loci as well. In contrast, prior studies from the authors' laboratory had demonstrated that the filamentation deficiency and attenuated virulence of hwp1D mutants were fully restored in rescued strains in which URA3 was integrated at the HWP1 locus. This discrepancy prompted a reinvestigation of these mutants. A series of congenic strains were constructed which demonstrated that the filamentation and virulence defects of a homozygous hwp1D mutant could be rescued without introduction of a functional HWP1 allele. Despite the absence of detectable differences in URA3 expression, analysis of suppressor mutations suggested that reduced URA3 expression gave rise to the mutant phenotypes. Several independent spontaneous suppressor mutations that restored filamentation to strains of genotype hwp1D : : hisG-URA3-hisG/hwp1D : : hisG had acquired a tandem duplication of the hisG-URA3-hisG marker cassette. The hwp1 null mutant and rescued strains differed by the presence or absence of flanking hisG sequence. Substitution of the hisG-URA3-hisG insert of the hwp1 null mutant with URA3 alone largely rescued the filamentation and virulence phenotypes. The presence of a single copy of hisG adjacent to URA3 had no effect. It is concluded that flanking direct repeats of hisG, present as part of a recyclable disruption cassette, negatively influenced URA3 expression and are responsible for the previously reported phenotypes of the hwp1 mutants.

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“…An inverse correlation between 5-methylcytosine content and gene expression has been observed (12,25), although more important than total amount seems to be their upstream location toward the particular gene (17,28). In fungal DNA, the content of 5-methylcytosine is variable depending on the organism analyzed (1, 18) (one species contains N6-methyl adenine [20]), and the role of DNA methylation on gene regulation during fungal development has been suggested for several fungi (2,16,23,24).…”

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confidence: 99%

DNA methylation and polyamines in regulation of development of the fungus Mucor rouxii

1988

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DNA from intact or spherically growing spores of Mucor rouxuii is highly methylated, whereas DNA from germlings has low levels of methylation. DNA from spores incubated with hydroxyurea or 1,4-diaminobutanone is also highly methylated. The reversal of the effect of 1,4-diaminobutanone by azacytidine correlated with DNA hypomethylation. These data suggest that the change in growth pattern from spherical to polarized correlates with the degree of DNA methylation and that this, in turn, may be controlled by polyamine levels.

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Different levels of DNA methylation in yeast and mycelial forms of Candida albicans

Cited by 43 publications

References 13 publications

Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids fromCandida albicans

Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids fromCandida albicans

Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans

DNA methylation and polyamines in regulation of development of the fungus Mucor rouxii

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