Morphogenesis‐independent regulation of actin transcript levels in the pathogenic yeast <i>Candida albicans</i>

Delbrück, Sebastian; Ernst, Joachim F.

doi:10.1111/j.1365-2958.1993.tb00956.x

Cited by 73 publications

(56 citation statements)

References 28 publications

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“…One such feedback system involving the high-affinity cAMP PDE has already been proven in mammalian cells (Zinman & Hollenberg, 1974;Loten, 1978;Gettys et al, 1987), where cAMP hydrolysis plays an important role in terminating the hormonal stimulus and is one of several mechanisms inducing desensitization in the target cells. A similar mechanism is apparent in Candida as illustrated in the & Ernst, 1993) and incubated at 37 6C. Seven days later hyphae were excised from the edges of the colonies, transferred to solid SD and incubated at 30 6C for up to 5 days.…”

Section: Discussionmentioning

confidence: 98%

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

Jung

Stateva

2003

Microbiology

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The cAMP-dependent pathway, which regulates yeast-to-hypha morphogenesis in Candida albicans, is controlled by changes in cAMP levels determined by the processes of synthesis and hydrolysis. Both low-and high-affinity cAMP phosphodiesterases are encoded in the C. albicans genome. CaPDE2, encoding the high-affinity cAMP phosphodiesterase, has been cloned and shown to be toxic in Saccharomyces cerevisiae upon overexpression under pGAL1, but functional under the moderate pMET3. Deletion of CaPDE2 causes elevated cAMP levels and responsiveness to exogenous cAMP, higher sensitivity to heat shock, severe growth defects at 42 6C and highly reduced levels of EFG1 transcription. In vitro in hypha-inducing liquid medium CaPDE2, deletion prohibits normal hyphal, but not pseudohyphal growth. On solid medium capde2 mutants form aberrant hyphae, with fewer branches and almost no lateral buds, which are deficient in hypha-to-yeast reversion. The phenotypic defects of capde2 mutants show that the cAMP-dependent pathway plays specific roles in hyphal and pseudohyphal development, its regulatory role however, being greater in liquid than on solid medium in vitro. The increased expression of CaPDE2 after serum addition correlates well with a drop in cAMP levels following the initial rise in response to the hyphal inducer. These results suggest that Capde2p mediates a desensitization mechanism by lowering basal cAMP levels in response to environmental stimuli in C. albicans.

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Section: Discussionmentioning

confidence: 98%

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

Jung

Stateva

2003

Microbiology

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“…The expression of many other C. albicans genes fluctuates in response to the inducing conditions during the yeast-to-hypha transition rather than to morphogenesis itself. These genes encode proteins involved in wideranging functions such as glycolysis (ADH1, PYK1, GPM1, and PGK1 [67]), protein synthesis and folding (TEF3, RP10, and HSP90 [65,66,69]), cell wall biosynthesis (CHS1, CHS2, CHS3, and GFA1 [10,24,59]), and formation of the cytoskeleton (ACT1 [13,66]). We know of only one C. albicans mRNA (HST7) that remains at relatively constant levels during the yeast-to-hypha transition.…”

Section: Discussionmentioning

confidence: 99%

The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins

et al. 1996

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A hyphally regulated gene (HYR1) from the dimorphic human pathogenic fungus Candida albicans was isolated and characterized. Northern (RNA) analyses showed that the HYR1 mRNA was induced specifically in response to hyphal development when morphogenesis was stimulated by serum addition and temperature elevation, increases in both culture pH and temperature, or N-acetylglucosamine addition. The HYR1 gene sequence revealed a 937-codon open reading frame capable of encoding a protein with an N-terminal signal sequence, a C-terminal glycosylphosphatidylinositol-anchoring domain, 17 potential N glycosylation sites, and a large domain rich in serine and threonine (51% of 230 residues). These features are observed in many yeast cell wall proteins, but no homologs are present in the databases. In addition, Hyr1p contained a second domain rich in glycine, serine, and asparagine (79% of 239 residues). The HYR1 locus in C. albicans CAI4 was disrupted by "Ura-blasting," but the resulting homozygous ⌬hyr1/⌬hyr1 null mutant displayed no obvious morphological phenotype. The growth rates for yeast cells and hyphae and the kinetics of germ tube formation in the null mutant were unaffected. Aberrant expression of HYR1 in yeast cells, when an ADH1-HYR1 fusion was used, did not stimulate hyphal formation in C. albicans or pseudohyphal growth in Saccharomyces cerevisiae. HYR1 appears to encode a nonessential component of the hyphal cell wall.Candida albicans is a major fungal pathogen in humans (44,45). Most frequently it causes superficial, irritating infections of the oral and urogenital tracts. However, serious deep-seated or systemic infections can develop, particularly in immunocompromised individuals.A number of factors are thought to promote the virulence of C. albicans. Many of these factors relate to properties of the C. albicans cell surface, for example, the ability to adhere to host tissues (7,8,27) and the immunomodulatory effects of various cell wall components (40,72). Another potential virulence factor is the ability to undergo a morphological transition from a budding yeast to a hyphal form, but this has not been established unambiguously (12,39,48,57,60,61). Changes in the C. albicans cell surface accompany the morphological transition (9,15,16,31,38,64), and hence morphogenesis is intimately linked with other virulence factors such as adherence. Processes germane to the regulation of the yeast-to-hypha transition are therefore important in establishing the role of this transition in the pathogenicity of C. albicans.Several factors influenced our experimental approach. First, classical genetic approaches were inappropriate because C. albicans is asexual and diploid (55). Second, nonstandard usage of the CTG codon in C. albicans (52,53,78) precluded the use of standard reporter genes, and until recently (62), no sensitive reporter genes for C. albicans were available. Hence, we attempted to identify C. albicans genes which are regulated specifically in response to morphogenesis. Using various approaches, we identifie...

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“…Similarly, use of a neutral pH in combination with an elevated temperature accelerated filamentation, but there was no clear correlation to the SEC20 transcript level. Thus, we conclude that the level of SEC20 expression, like the expression of many other genes (11,47) does not directly reflect filament formation but may depend on other factors. We also determined that the SEC20 transcript was not induced by heat shock but increased during the early growth phase (data not shown).…”

Section: Fig 2 Disruption Of Sec20 Alleles (A)mentioning

confidence: 99%

Divergence of Eukaryotic Secretory Components: the Candida albicans Homolog of the Saccharomyces cerevisiae Sec20 Protein Is N Terminally Truncated, and Its Levels Determine Antifungal Drug Resistance and Growth

Weber¹,

Santore

Ernst³

et al. 2001

J Bacteriol

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Sec20p is a component of the yeast Saccharomyces cerevisiae secretory pathway that does not have a close homolog in higher eukaryotic cells. To verify the function of Sec20p in other fungal species, we characterized the gene encoding a Sec20p homolog in the human fungal pathogen Candida albicans. The deduced protein has 27% identity with, but is missing about 100 N-terminal residues compared to S. cerevisiae Sec20p, which is part of the cytoplasmic tail interacting with the cytoplasmic protein Tip20p. Because a strain lacking both C. albicans SEC20 alleles could not be constructed, we placed SEC20 under transcriptional control of two regulatable promoters, MET3p and PCK1p. Repression of SEC20 expression in these strains prevented (MET3p-SEC20 allele) or retarded (PCK1p-SEC20 allele) growth and led to the appearance of extensive intracellular membranes, which frequently formed stacks. Reduced SEC20 expression in the PCK1p-SEC20 strain did not affect morphogenesis but led to a series of hypersensitivity phenotypes including supersensitivity to aminoglycoside antibiotics, to nystatin, to sodium dodecyl sulfate, and to cell wall inhibitors. These results demonstrate the occurrence and function of Sec20p in a fungal species other than S. cerevisiae, but the lack of the N-terminal domain and the apparent absence of a close TIP20 homolog in the C. albicans genome also indicate a considerable diversity in mechanisms of retrograde vesicle traffic in eukaryotes.

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Morphogenesis‐independent regulation of actin transcript levels in the pathogenic yeast Candida albicans

Cited by 73 publications

References 28 publications

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins

Divergence of Eukaryotic Secretory Components: the Candida albicans Homolog of the Saccharomyces cerevisiae Sec20 Protein Is N Terminally Truncated, and Its Levels Determine Antifungal Drug Resistance and Growth

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