Transcriptional Response of Candida albicans to Hypoxia: Linkage of Oxygen Sensing and Efg1p-regulatory Networks

Setiadi, Eleonora; Doedt, Thomas; Cottier, Fabien; Noffz, Christine; Ernst, Joachim F.

doi:10.1016/j.jmb.2006.06.040

Cited by 165 publications

(268 citation statements)

References 51 publications

Supporting

Mentioning

243

Contrasting

Unclassified

Order By: Relevance

“…Hyphaspecific genes are not the only genes affected in efg1 mutants as determined by genome-wide transcription analyses (Sohn et al, 2003;Doedt et al, 2004;Harcus et al, 2004;Cao et al, 2006;Setiadi et al, 2006), and Efg1 also regulates other cellular processes and development (Lo et al, 1997;Stoldt et al, 1997;Sonneborn et al, 1999;Srikantha et al, 2000;Zordan et al, 2007). Phd1, a member of the APSES family in S. cerevisiae, binds to DNA nonspecifically in vitro (Ho et al, 2006), but it binds specific promoters in vivo (Borneman et al, 2006); therefore, Phd1 is thought to use additional cofactors to achieve sequence-specific binding in yeast (Ho et al, 2006).…”

Section: Efg1 Interacts With Nua4 In Vivo and Recruits Nua4 To Promotmentioning

confidence: 99%

“…It is suggested to function downstream of the cAMP/protein kinase A (PKA) pathway in hyphal development (Sonneborn et al, 2000;Bockmuhl and Ernst, 2001), and both Efg1 and PKA are required for the induction of hypha-specific genes. However, Efg1 also regulates other genes that are not modulated by the cAMP pathway (Sohn et al, 2003;Doedt et al, 2004;Harcus et al, 2004;Setiadi et al, 2006). Numerous in vitro and in vivo studies with efg1 mutants have demonstrated that Efg1 is important for C. albicans virulence and for the interactions of C. albicans with endothelial and epithelia cells, as well as biofilm formation and catheter infection (Lo et al, 1997;Phan et al, 2000;Dieterich et al, 2002;Lewis et al, 2002;Ramage et al, 2002;Garcia-Sanchez et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

Lü

Mao

et al. 2008

MBoC

102

View full text Add to dashboard Cite

Efg1 is essential for hyphal development and virulence in the human pathogenic fungus Candida albicans. How Efg1 regulates gene expression is unknown. Here, we show that Efg1 interacts with components of the nucleosome acetyltransferase of H4 (NuA4) histone acetyltransferase (HAT) complex in both yeast and hyphal cells. Deleting YNG2, a subunit of the NuA4 HAT module, results in a significant decrease in the acetylation level of nucleosomal H4 and a profound defect in hyphal development, as well as a defect in the expression of hypha-specific genes. Using chromatin immunoprecipitation, Efg1 and the NuA4 complex are found at the UAS regions of hypha-specific genes in both yeast and hyphal cells, and Efg1 is required for the recruitment of NuA4. Nucleosomal H4 acetylation at the promoters peaks during initial hyphal induction in an Efg1-dependent manner. We also find that Efg1 bound to the promoters of hypha-specific genes is critical for recruitment of the Swi/Snf chromatin remodeling complex during hyphal induction. Our data show that the recruitment of the NuA4 complex by Efg1 to the promoters of hypha-specific genes is required for nucleosomal H4 acetylation at the promoters during hyphal induction and for subsequent binding of Swi/Snf and transcriptional activation. INTRODUCTIONCandida albicans has emerged as one of the most prevalent opportunistic fungal pathogens in humans. It causes mucosal as well as systemic candidiasis, especially in immunocompromised patients. C. albicans can undergo reversible morphogenetic transitions between budding yeast, pseudohyphal, and hyphal growth forms. Its unique ability to switch from yeast to hyphal growth in response to various signals is essential for its pathogenicity.Central to the yeast-to-hypha transition is the transcription factor Efg1, a member of the Asm1p, Phd1p, Sok2p, Efg1p, and StuAp (APSES) family of fungal proteins that regulate cellular differentiation in ascomycetes. Members of this family share a conserved DNA binding domain. Efg1 is an essential regulator of hyphal development, chlamydospore formation, and white-opaque phenotypic switching in C. albicans (Lo et al., 1997;Stoldt et al., 1997;Sonneborn et al., 1999;Srikantha et al., 2000;Zordan et al., 2007). It is suggested to function downstream of the cAMP/protein kinase A (PKA) pathway in hyphal development (Sonneborn et al., 2000;Bockmuhl and Ernst, 2001), and both Efg1 and PKA are required for the induction of hypha-specific genes. However, Efg1 also regulates other genes that are not modulated by the cAMP pathway (Sohn et al., 2003;Doedt et al., 2004;Harcus et al., 2004;Setiadi et al., 2006). Numerous in vitro and in vivo studies with efg1 mutants have demonstrated that Efg1 is important for C. albicans virulence and for the interactions of C. albicans with endothelial and epithelia cells, as well as biofilm formation and catheter infection (Lo et al., 1997;Phan et al., 2000;Dieterich et al., 2002;Lewis et al., 2002;Ramage et al., 2002;Garcia-Sanchez et al., 2004). Despite its importance, molecula...

show abstract

Section: Efg1 Interacts With Nua4 In Vivo and Recruits Nua4 To Promotmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

Lü

Mao

et al. 2008

MBoC

102

View full text Add to dashboard Cite

show abstract

“…Candida albicans-Candida albicans is an important human fungal pathogen that causes superficial skin infections as well as deep-seated infections, suggesting that its ability to switch between normoxia and hypoxia is a major determinant of its virulence (68). In C. albicans little is known about mechanisms utilized by this yeast to adapt to hypoxic microenvironments.…”

Section: Fungi With the Srebp Analogue Upc2pmentioning

confidence: 99%

“…Second, S. cerevisiae genes involved in glycolysis and fermentation are not stimulated by hypoxia (25,70), but hypoxia induces these genes and genes involved in hyphal growth in C. albicans while genes of oxidative metabolism are repressed (68). During normoxic conditions the global transcription factor Efg1p regulates the expression of genes involved in glycolysis and respiration, but it has no role in controlling the expression of respiratory genes and is not required to upregulate glycolytic gene expression in hypoxia (68,71). Efg1p also promotes filamentation under normoxic conditions.…”

Section: Fungi With the Srebp Analogue Upc2pmentioning

confidence: 99%

Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi?

Grahl¹,

Cramer²

2009

Med. Mycology

View full text Add to dashboard Cite

SummaryOver the past two decades, the incidence of fungal infections has dramatically increased. This is primarily due to increases in the population of immunocompromised individuals attributed to HIV/ AIDS pandemic and immunosuppression therapies associated with organ transplantation, cancer, and other diseases where new immunomodulatory therapies are utilized. Significant advances have been made in understanding how fungi cause disease, but clearly much remains to be learned about the pathophysiology of these often lethal infections.Fungal pathogens face numerous environmental challenges as they colonize and infect mammalian hosts. Regardless of a pathogen's complexity, its ability to adapt to environmental changes is critical for its survival and ability to cause disease. For example, at sites of fungal infections, the significant influx of immune effector cells and the necrosis of tissue by the invading pathogen generate hypoxic microenvironments to which both the pathogen and host cells must adapt in order to survive. However, our current knowledge of how pathogenic fungi adapt to and survive in hypoxic conditions during fungal pathogenesis is limited. Recent studies have begun to observe that the ability to adapt to various levels of hypoxia is an important component of the virulence arsenal of pathogenic fungi. In this review, we focus on known oxygen sensing mechanisms that non-pathogenic and pathogenic fungi utilize to adapt to hypoxic microenvironments and their possible relation to fungal virulence.

show abstract

“…Most virulence factors, including adhesion, invasion, and yeast-to-hypha transition, localize on the cell wall, such as Pga4p, Pga7p, Alg2p, Pmt4p, Mnn46p, Iff11p. [21][22][23][24][25][26][27][28] The cell wall also plays an important role in crucial host-fungus interactions that facilitate the establishment of human mycoses. Thus the cell wall proteins might be ideal vaccine targets to induce protective immune response in host.…”

Section: )mentioning

confidence: 99%

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

Wang

Yan

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.

show abstract

Transcriptional Response of Candida albicans to Hypoxia: Linkage of Oxygen Sensing and Efg1p-regulatory Networks

Cited by 165 publications

References 51 publications

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi?

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

Contact Info

Product

Resources

About