Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans

Abstract

SummaryTreatments that perturb DNA synthesis or mitosis will activate checkpoints that prevent cell cycle progression and cell proliferation. In yeast-form cells of the fungal pathogen Candida albicans , exposure to hydroxyurea (HU) or shutting off expression of the polo-like kinase CaCDC5 blocked nuclear division and spindle elongation, but activated a highly polarized growth mode. We have used transcription profiling both to characterize the initiation and progression of this polar growth pattern and to determine how cell elongation may be linked to the cell cycle in C. albicans . Different gene expression patterns during early stages of cell elongation support the concept that CaCdc5p-depleted and HU-exposed cells were blocked at different stages of the cell cycle, and suggest that different signals may generate the common polarized growth phenotype. Consistent with this, BUB2 expression was modulated in CaCdc5p-depleted cells, and absence of BUB2 prevented the maintenance of cell polarization, resulting in multibudded, pseudohyphal cells with constrictions. In contrast, HU-induced filaments did not modulate or require BUB2 , but were dependent on the GTPase Ras1p. However, at later stages of cell elongation, transcription profiles were more similar, and comparisons with serum-induced hyphae revealed that the cell cycle-arrested filaments expressed several targets of the hyphal signalling pathways. Thus, arresting the yeast cell cycle in S or M phase generates a polarized growth pattern through different mechanisms in C. albicans , and maintenance of the polar growth mode can ultimately lead to the expression of hyphal-associated cell wall and virulence-related factors, in the absence of any external stimuli.

Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

“…The filaments resemble serum-induced hyphae, and filament formation is independent of Cph1 or Efg1 but requires Cyr1/Cdc35 (11). Microarray experiments confirmed the resemblance of cell cycle-arrested filaments to serum-induced hyphae, as in both cases several targets of hyphasignaling pathways were expressed (10).…”

Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2

“…Previous work demonstrated that lower ergosterol levels, caused by ergosterol biosynthesis inhibitors, such as azoles, have an inhibitory effect on hypha formation (63,64). However, elongated growth forms resulting from impaired Hsp90 function are not considered true hyphae (14,65,66). Consistent with the relationship between ergosterol depletion and C. albicans morphogenesis mentioned by Victoria et al (67), we report a correlation between ergosterol content and elongated growth caused by impairment of Hsp90 function.…”

Morphogenesis in Candida albicans

“…Transcriptional profiling of HU-treated and cdc5 mutant strains showed different expression patterns. The HU-arrested cells require Ras1p for the extended bud growth, and the cdc5-arrested cells require Bub2p function for the formation of the extended buds (6). The different triggers stop the cells at different points in the cell cycle, and the hyperpolarized bud does not arise because the cells are trapped at a point corresponding to normal polarized growth.…”