The same receptor, G protein, and mitogen-activated protein kinase pathway activate different downstream regulators in the alternative white and opaque pheromone responses of Candida albicans.
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ABSTRACT:
SUBMITTER: Yi S
PROVIDER: S-EPMC2262975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white-opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10-fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white-opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white-opaque switching to cellular physiology.
| S-EPMC4981270 | biostudies-literature
Project description:Modes of sexual reproduction in eukaryotic organisms are extremely diverse. The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent. In this study, we report that functionally- and morphologically-differentiated white and opaque cells show a coordinated behavior during mating. Although white cells are mating-incompetent, they can produce sexual pheromones when treated with pheromones of the opposite mating type or by physically interacting with opaque cells of the opposite mating type. In a co-culture system, pheromones released by white cells induce opaque cells to form mating projections, and facilitate both opposite- and same-sex mating of opaque cells. Deletion of genes encoding the pheromone precursor proteins and inactivation of the pheromone response signaling pathway (Ste2-MAPK-Cph1) impair the promoting role of white cells (MTLa) in the sexual mating of opaque cells. White and opaque cells communicate via a paracrine pheromone signaling system, creating an environment conducive to sexual mating. This coordination between the two different cell types may be a trade-off strategy between sexual and asexual lifestyles in C. albicans.
| S-EPMC4199524 | biostudies-literature
Project description:The opportunistic pathogen Candida albicans undergoes a parasexual mating cycle in which cells must switch from the conventional "white" form to the alternative "opaque" form to become mating competent. Pheromones secreted by opaque cells induce the formation of polarized mating projections and result in cell-cell conjugation. In contrast, white cells are unable to undergo mating, but can still respond to pheromone by expression of adhesion genes that promote biofilm formation. In this study, we have analyzed the dual ability of pheromones to activate mating by opaque cells and biofilm formation by white cells. We first show that there is considerable plasticity in interactions between the α pheromone and its receptor, Ste2, by analysis of analogs of the α pheromone. Significantly, substituted forms of α pheromone can induce a response in opaque cells and this is sufficient to drive same-sex a-a cell fusion and homothallic mating. In addition, pheromone analogs were able to induce adhesion and biofilm formation in white cells of C. albicans. Because of the observed plasticity in pheromone signaling, we subsequently tested putative pheromones from multiple Candida species and identified nonnative ligands that can induce self-mating and biofilm responses in C. albicans. Our findings demonstrate that environmental signals can initiate C. albicans parasexual reproduction and biofilm formation, and highlight the role of the pheromone-signaling apparatus in mediating these functions.
| S-EPMC3038756 | biostudies-literature
Project description:In Candida albicans, the a1-alpha2 complex represses white-opaque switching, as well as mating. Based upon the assumption that the a1-alpha2 corepressor complex binds to the gene that regulates white-opaque switching, a chromatinimmunoprecipitation-microarray analysis strategy was used to identify 52 genes that bound to the complex. One of these genes, TOS9, exhibited an expression pattern consistent with a "master switch gene." TOS9 was only expressed in opaque cells, and its gene product, Tos9p, localized to the nucleus. Deletion of the gene blocked cells in the white phase, misexpression in the white phase caused stable mass conversion of cells to the opaque state, and misexpression blocked temperature-induced mass conversion from the opaque state to the white state. A model was developed for the regulation of spontaneous switching between the opaque state and the white state that includes stochastic changes of Tos9p levels above and below a threshold that induce changes in the chromatin state of an as-yet-unidentified switching locus. TOS9 has also been referred to as EAP2 and WOR1.
| S-EPMC1595353 | biostudies-literature
Project description:ObjectivesCandida albicans, a polymorphic yeast, is one of the most common, opportunistic fungal pathogens of humans. Among the different morphological forms, opaque form is one of the least-studied ones. This opaque phenotype is essential for mating and is also reported to be involved in colonizing the gastrointestinal tract. Considering the significance of the clinical and sexual reproduction of C. albicans, we have investigated the morphophysiological modulations in opaque form using a proteomic approach.Data descriptionIn the current investigation, we have used Micro-Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analysis to create a protein profile for opaque-specific proteins. Whole-cell proteins from C. albicans (ATCC10231) cells that had been cultured for seven days on synthetic complete dextrose (SCD) medium in both as an opaque (test) and as a white (control) form cells were extracted, digested, and identified using LC-MS/MS. This information is meant to serve the scientific community and represents the proteome profile (SWATH Spectral Libraries) of C. albicans opaque form.
| S-EPMC10759580 | biostudies-literature
Project description:Candida albicans strains that are homozygous at the mating type locus (MTLa or MTLalpha) can spontaneously switch at a low frequency from the normal yeast cell morphology (white) to an elongated cell type (opaque), which is the mating-competent form of the fungus. The ability to switch reversibly between these two cell types also contributes to the pathogenicity of C. albicans, as white and opaque cells are differently adapted to specific host niches. We found that in strain WO-1, a strain in which genomic alterations have occurred, but not in other tested strains, switching from the white to the opaque phase can also be induced by environmental conditions. Transient incubation of white cells under anaerobic conditions programmed the cells to switch en masse to the opaque phase. The anaerobic induction of white-opaque switching was controlled by the transcription factor CZF1, which in heterozygous MTLa/alpha cells regulates filamentous growth under embedded, hypoxic conditions. Intriguingly, passage of white cells of strain WO-1 through the mouse intestine, a host niche in which the cells are likely to be exposed to anaerobic conditions, resulted in a strongly increased frequency of switching to the opaque phase. These results demonstrate that white-opaque switching is not only a spontaneous process but, in combination with genomic alterations, can also be induced by environmental signals, suggesting that switching and mating of C. albicans may occur with high efficiency in appropriate niches within its human host.
| S-EPMC2405950 | biostudies-literature
Project description:Modes of sexual reproduction in eukaryotic organisms are highly diversified. The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent. In this study, we report that functionally and morphologically differentiated white and opaque cells show a coordinating behavior in the process of mating. Although white cells are mating-incompetent, they are induced to produce sexual pheromones when treated with opposite pheromones or interacted with opaque cells of an opposite mating type. In a co-culture system, pheromones released by white cells induce opaque cells to form mating projections and thus facilitate both opposite- and same-sex mating of opaque cells. Deletion of genes encoding the pheromone precursor proteins and inactivation of the pheromone response signaling pathway (Ste2-MAPK-Cph1) impair the promoting role of white cells (MTLa) in sexual mating of opaque cells. White and opaque cells communicate via a paracrine pheromone signaling and thus create an environment conducive to sexual mating. This coordination behavior of the two different cell types may be a trade-off strategy between sexual and asexual lifestyles in C. albicans.
2014-10-23 | GSE56039 | GEO
Project description:To mate, Candida albicans must undergo homozygosis at the mating type-like locus MTL[1, 2], then switch from the white to opaque phenotype [3, 4]. Paradoxically, when opaque cells are transferred in vitro to 37 degrees C, the temperature of their animal host, they switch en masse to white [5-7], suggesting that their major niche might not be conducive to mating. It has been suggested that pheromones secreted by opaque cells of opposite mating type [8] or the hypoxic condition of host niches [9, 10] stabilize opaque cells. There is, however, an additional possibility, namely that CO(2), which achieves levels in the host 100 times higher than in air [11-13], stabilizes the opaque phenotype. CO(2) has been demonstrated to regulate the bud-hypha transition in C. albicans[14, 15], expression of virulence genes in bacteria [16], and mating events in Cryptococcus neoformans[14, 17]. We tested the possibility that CO(2) stabilizes the opaque phenotype, and found that physiological levels of CO(2) induce white-to-opaque switching and stabilize the opaque phenotype at 37 degrees C. It exerts this control equally under anaerobic and aerobic conditions. These results suggest that the high levels of CO(2) in the host induce and stabilize the opaque phenotype, thus facilitating mating.
| S-EPMC2667266 | biostudies-literature
Project description:In this study, we investigated the relationships among the pheromone components to identify how the MAPK proteins are coordinated through a scaffold that lacks a key domain. An attempt to bypass other components by artificially driving either Cst5 or Ste11 to the plasma membrane suggested that the interactions among the proteins are more complex than the linear cascade characterized in S. cerevisiae. Moreover, the findings suggest the MAPK proteins Hst7 and Ste11 regulate the translocation of Cst5 within the cytoplasm. Indeed, it appears that Ste11 interacts with Cst5 to generate a complex node to tether the downstream kinases where Ste11 can both act enzymatically on Hst7 as well as make the MAPK Cek1 available for phosphorylation and activation by Hst7.
2020-12-01 | GSE158062 | GEO
Project description:Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans.
| S-EPMC3280983 | biostudies-literature