COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans (original) (raw)
Related papers
Microbiology, 1999
In Candida albicans, three putative histidine kinase genes have been described thus far, including CaSLNI, CaNIKlICOSl and CaHKl. The encoded proteins for C. albicans, CaSlnlp and CaNiklp, which are similar to S l n l p from Saccharomyces cerevisiae and Nik-1 from Neurospora crassa, seem to function in osmoregulation and morphogenesis, respectively. Recently, the isolation of CaHKl, a putative histidine kinase gene from C. albicans has been reported. In addition t o the histidine and aspartyl domains located at its C-terminus as previously described, it is shown here that the N-terminal domain o f Cahklp contains a P-loop motif and a sequence which shows significant homology with the seven C-terminal domains of serinekhreonine kinases. The Ser/Thrhomologous domains of Cahklp could, in fact, correspond to its sensor sequence. CaHKl has been mapped to chromosome 2 and gene deletion studies were undertaken to understand its function. Acahkl mutants are phenotypically different from any other histidine kinase mutants thus far described either in C. albicans or in any other yeast or filamentous fungus. This study demonstrates that Acahkl mutants flocculate extensively in a genedosage-dependent manner under conditions which induce germ-tube formation, such as growth in medium 199 (pH 7.5). The flocculation occurs by an interaction along the hyphal surfaces, probably because of the altered expression o f one or more hyphal-cell-surface components in the Acahkl mutants. These results indicate that CaHKl could be involved in regulating their expression.
Hyphal growth in Candida albicans does not require induction of hyphal-specific gene expression
Molecular biology of the cell, 2015
Various stimuli, including N-acetylglucosamine (GlcNAc), induce the fungal pathogen Candida albicans to switch from budding to hyphal growth. Previous studies suggested that hyphal morphogenesis is stimulated by transcriptional induction of a set of genes that includes known virulence factors. To better understand hyphal development, we examined the role of GlcNAc metabolism using a triple mutant lacking the genes required to metabolize exogenous GlcNAc (hxk1Δ nag1Δ dac1Δ). Surprisingly, at low ambient pH (∼pH 4), GlcNAc stimulated this mutant to form hyphae without obvious induction of hyphal genes. This indicates that GlcNAc can stimulate a separate signal to induce hyphae that is independent of transcriptional responses. Of interest, GlcNAc could induce the triple mutant to express hyphal genes when the medium was buffered to a higher pH (>pH 5), which normally occurs after GlcNAc catabolism. Catabolism of GlcNAc raises the ambient pH rather than acidifying it, as occurs after...
Eukaryotic Cell, 2014
Prokaryotes and lower eukaryotes, such as yeasts, utilize two-component signal transduction pathways to adapt cells to environmental stress and to regulate the expression of genes associated with virulence. One of the central proteins in this type of signaling mechanism is the phosphohistidine intermediate protein Ypd1. Ypd1 is reported to be essential for viability in the model yeast Saccharomyces cerevisiae. We present data here showing that this is not the case for Candida albicans. Disruption of YPD1 causes cells to flocculate and filament constitutively under conditions that favor growth in yeast form. To determine the function of Ypd1 in the Hog1 mitogen-activated protein kinase (MAPK) pathway, we measured phosphorylation of Hog1 MAPK in ypd1⌬/⌬ and wild-type strains of C. albicans. Constitutive phosphorylation of Hog1 was observed in the ypd1⌬/⌬ strain compared to the wild-type strain. Furthermore, fluorescence microscopy revealed that green fluorescent protein (GFP)-tagged Ypd1 is localized to both the nucleus and the cytoplasm. The subcellular segregation of GFP-tagged Ypd1 hints at an important role(s) of Ypd1 in regulation of Ssk1 (cytosolic) and Skn7 (nuclear) response regulator proteins via phosphorylation in C. albicans. Overall, our findings have profound implications for a mechanistic understanding of two-component signaling pathways in C. albicans, and perhaps in other pathogenic fungi.
Journal of Biological Chemistry, 2001
Candida albicans, normally a human commensal, can cause fatal systemic infections under certain circumstances. Its unique ability to switch from yeast to hyphal growth in response to various environmental signals is inherent to its pathogenicity. Filamentation is regulated by multiple pathways including a Cph1-mediated mitogen-activated protein kinase pathway, an Efg1-mediated cAMP/PKA pathway, and a Cph2 pathway. To gain a general picture of how these various signaling pathways regulate differential gene expression during filamentation, we have constructed a partial C. albicans DNA array of 7,000 genes and used it to study the gene expression profiles using various mutants and growth conditions. By combining this novel technology with a new liquid medium in which cph1/cph1 is defective in filamentation, previously identified differentially expressed genes (ECE1, HWP1, HYR1, RBT1, SAPs5-6, and RBT4) are found to be regulated by all three pathways. In addition, two novel genes, DDR48 and YPL184, have been found to be differentially regulated during hyphal development and by all three pathways. This suggests that distinct filamentation signaling pathways converge to regulate a common set of differentially expressed genes. As one of the mechanisms for the observed convergence, we find that the transcription of a key regulator, TEC1, is regulated by Efg1 and Cph2. Importantly, most of the genes regulated by multiple filamentation pathways encode known virulence factors. Perhaps, C. albicans utilizes converging pathways to regulate its vital virulence factors to ensure its survival and pathogenicity in various host environments. Candida albicans is a common human commensal often associated with superficial colonization of the mucous epithelium. However, the incidence of fatal C. albicans infections, as well as drug-resistant strains, have increased dramatically in recent years in patients undergoing chemotherapy, transplantation, and in particular, in immunocompromised patients suffering from AIDS (1). C. albicans exhibits the ability to grow in a variety of reversible morphological forms (yeast, pseudohyphal, and hyphal) in response to various environmental signals (2). The ability of C. albicans to switch its mode of growth has been shown to be required for the pathogenicity of this fungus (3-5). Clearly a better understanding of the differentiation pathways which permit C. albicans to switch between the different morphological forms will reveal more about C. albicans pathogenesis. Multiple signaling pathways have been found to regulate filamentation. Cph1, a transcription factor homologous to Saccharomyces cerevisiae, Ste12, plays a role in hyphal development on certain solid media in C. albicans (6). As in S. cerevisiae, Cph1 in C. albicans is regulated by a mitogen-activated protein (MAP) 1 kinase cascade that includes Cst20, Hst7, and Cek1 (7-9). Mutants with homozygous deletions of the genes encoding these proteins all display a medium-specific defect in hyphal development on certain solid media. Efg1, a basic helixloop-helix protein similar to Phd1 of S. cerevisiae and StuA of Aspergillus nidulans, plays a major role in regulating hyphal development in C. albicans (3, 10). efg1/efg1 null mutant strains fail to produce hyphae under many conditions, including the presence of serum, which is one of the strongest inducers of hyphal formation (3, 10). Efg1 acts downstream of the cAMP/ protein kinase A (PKA) signaling pathway (11, 12). The Efg1mediated cAMP pathway is thought to be distinct from the Cph1-mediated MAP kinase pathway, because the cph1/cph1 efg1/efg1 double mutant has a greater defect in hyphal development and virulence than either single mutant (3). Cph1 and Efg1 are the first identified regulators of hyphal development. Recently, a new member of the TEA/ATTS family of transcription factors, Tec1, has been shown to regulate hyphal development and virulence in C. albicans (13). More recently, Cph2, a basic helix loop helix protein of the Myc subfamily, is found to regulate hyphal development in a medium-specific manner (34). Its activity is mediated, in part, through regulating TEC1 transcriptional induction. Condition-specific hyphal regulators such as Czf1 and Rim101/Prr2 have also been identified in C. albicans (14, 15). Czf1, a potential transcription factor with a zinc finger motif, regulates filamentous growth in response to embedded conditions. Rim101, a transcription factor with a zinc-finger domain similar to PacC of A. nidulans and Rim101 of S. cerevisiae, is involved in a pH-responsive pathway (15-18). Rim101-activated hyphal development requires Efg1 (15). C. albicans also has negative regulators of hyphal development. Tup1, a global transcriptional co-repressor, is required to maintain the organism in yeast form, as the disruption of TUP1 causes the organism to filament under conditions that normally induce it to grow as yeast (19). Tup1-mediated repression
Mycoses, 1999
SummaryCandida albicans is an important pathogen of the immunocompromised patient. Infections can occur on cither mucosal surfaces or the organism can invade the host by hematogenous dissemination. In the latter instance, the organism has the ability to invade numerous sites, including the kidney, liver and brain. Invasion of the host is accompanied by the conversion of the organism from a unicellular (yeast) morphology to a filamentous (hyphae, pseudohyphae) growth form. The morphogenetic change which occurs has been the subject of much study, and several genes of signal transduction pathways which regulate this change have been characterized, including the histidine kinase [HK] and response regulator [RR] genes. The HKs of C. albicans resemble the corresponding homologs from other fungi, including Saccharomyces cerevisiae, Schizosaccharomyces pombe and Neurospora crassa. We have characterized and functionally determined the roles of both a histidine kinase protein (Chk1p) and a re...
1999
Updated information and services can be found at: These include: REFERENCES http://jb.asm.org/content/181/10/3058#ref-list-1 at: This article cites 74 articles, 43 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on September 15, 2014 by guest http://jb.asm.org/ Downloaded from on September 15, 2014 by guest
Ras1Induced Hyphal Development in Candida albicans Requires the Formin Bni1
Eukaryotic Cell, 2005
Updated information and services can be found at: These include: REFERENCES http://ec.asm.org/content/4/10/1712#ref-list-1 at: This article cites 44 articles, 21 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on July 15, 2014 by guest http://ec.asm.org/ Downloaded from on July 15, 2014 by guest http://ec.asm.org/
Whole-Genome Analysis of Two-Component Signal Transduction Genes in Fungal Pathogens
Eukaryotic Cell, 2003
Updated information and services can be found at: These include: REFERENCES http://ec.asm.org/content/2/6/1151#ref-list-1 at: This article cites 57 articles, 21 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: