Dosage-dependent roles of the Cwt1 transcription factor for cell wall architecture, morphogenesis, drug sensitivity and virulence in Candida albicans

Yeast ◽  
2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Inmaculada Moreno ◽  
Mar��a Martinez-Esparza ◽  
Leslie Carolina Laforet ◽  
Rafael Sentandreu ◽  
Joachim F. Ernst ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Drug Sensitivity ◽  
Cell Wall Architecture

scholarly journals The zinc cluster transcription factor Czf1 regulates cell wall architecture and integrity in Candida albicans

2021 ◽  
Author(s):  
Austin Mottola ◽  
Bernardo Ramírez‐Zavala ◽  
Kerstin Hünniger ◽  
Oliver Kurzai ◽  
Joachim Morschhäuser
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Zinc Cluster ◽  
Cell Wall Architecture

scholarly journals Candida albicans Ecm33p Is Important for Normal Cell Wall Architecture and Interactions with Host Cells

2006 ◽  
Vol 5 (1) ◽  
pp. 140-147 ◽  
Author(s):  
Raquel Martinez-Lopez ◽  
Hyunsook Park ◽  
Carter L. Myers ◽  
Concha Gil ◽  
Scott G. Filler
Keyword(s):  
Endothelial Cells ◽  
Cell Wall ◽  
Candida Albicans ◽  
Epithelial Cells ◽  
Normal Cell ◽  
Cell Wall Integrity ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Oral Epithelial ◽  
Cell Wall Architecture

ABSTRACT Candida albicans ECM33 encodes a glycosylphosphatidylinositol-linked cell wall protein that is important for cell wall integrity. It is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis. To identify potential mechanisms through which Ecm33p contributes to virulence, we investigated the interactions of C. albicans ecm33Δ mutants with endothelial cells and the FaDu oral epithelial cell line in vitro. The growth rate of blastospores of strains containing either one or no intact copies of ECM33 was 50% slower than that of strains containing two intact copies of ECM33. However, all strains germinated at the same rate, forming similar-length hyphae on endothelial cells and oral epithelial cells. Strains containing either one or no intact copies of ECM33 had modestly reduced adherence to both types of host cells, and a markedly reduced capacity to invade and damage these cells. Saccharomyces cerevisiae expressing C. albicans ECM33 did not adhere to or invade epithelial cells, suggesting that Ecm33p by itself does not act as an adhesin or invasin. Examination of ecm33Δ mutants by transmission electron microscopy revealed that the cell wall of these strains had an abnormally electron-dense outer mannoprotein layer, which may represent a compensatory response to reduced cell wall integrity. The hyphae of these mutants also had aberrant surface localization of the adhesin Als1p. Collectively, these results suggest that Ecm33p is required for normal cell wall architecture as well as normal function and expression of cell surface proteins in C. albicans.

scholarly journals Role of Transcription Factor CaNdt80p in Cell Separation, Hyphal Growth, and Virulence in Candida albicans

2010 ◽  
Vol 9 (4) ◽  
pp. 634-644 ◽  
Author(s):  
Adnane Sellam ◽  
Christopher Askew ◽  
Elias Epp ◽  
Faiza Tebbji ◽  
Alaka Mullick ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Cell Separation ◽  
Hyphal Growth ◽  
Functional Domain ◽  
Transcription Factor Family ◽  
Content Type ◽  
Genes Encoding

ABSTRACT The NDT80/PhoG transcription factor family includes ScNdt80p, a key modulator of the progression of meiotic division in Saccharomyces cerevisiae. In Candida albicans, a member of this family, CaNdt80p, modulates azole sensitivity by controlling the expression of ergosterol biosynthesis genes. We previously demonstrated that CaNdt80p promoter targets, in addition to ERG genes, were significantly enriched in genes related to hyphal growth. Here, we report that CaNdt80p is indeed required for hyphal growth in response to different filament-inducing cues and for the proper expression of genes characterizing the filamentous transcriptional program. These include noteworthy genes encoding cell wall components, such as HWP1, ECE1, RBT4, and ALS3. We also show that CaNdt80p is essential for the completion of cell separation through the direct transcriptional regulation of genes encoding the chitinase Cht3p and the cell wall glucosidase Sun41p. Consistent with their hyphal defect, ndt80 mutants are avirulent in a mouse model of systemic candidiasis. Interestingly, based on functional-domain organization, CaNdt80p seems to be a unique regulator characterizing fungi from the CTG clade within the subphylum Saccharomycotina. Therefore, this study revealed a new role of the novel member of the fungal NDT80 transcription factor family as a regulator of cell separation, hyphal growth, and virulence.

scholarly journals Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86270 ◽  
Author(s):  
Yolanda Delgado-Silva ◽  
Catarina Vaz ◽  
Joana Carvalho-Pereira ◽  
Catarina Carneiro ◽  
Eugénia Nogueira ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Cell Wall Biogenesis

scholarly journals Nanoscopic Cell Wall Architecture of an Immunogenic Ligand in Candida Albicans during Antifungal Drug Treatment

2016 ◽  
Vol 110 (3) ◽  
pp. 483a
Author(s):  
Aaron K. Neumann ◽  
Jia Lin ◽  
Michael J. Wester ◽  
Matthew S. Graus ◽  
Keith A. Lidke
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Drug Treatment ◽  
Antifungal Drug ◽  
Cell Wall Architecture

scholarly journals The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants

2002 ◽  
Vol 35 (3) ◽  
pp. 601-611 ◽  
Author(s):  
J. C. Kapteyn ◽  
L. L. Hoyer ◽  
J. E. Hecht ◽  
W. H. Müller ◽  
A. Andel ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Wild Type ◽  
Cell Wall Architecture

scholarly journals Activation of Cph1 causes ß(1,3)-glucan unmasking in Candida albicans and attenuates virulence in mice in a neutrophil-dependent manner

2021 ◽  
Vol 17 (8) ◽  
pp. e1009839
Author(s):  
Andrew S. Wagner ◽  
Trevor J. Hancock ◽  
Stephen W. Lumsdaine ◽  
Sarah J. Kauffman ◽  
Mikayla M. Mangrum ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Immune System ◽  
Mapk Pathway ◽  
Host Immune System ◽  
Dependent Manner ◽  
Antibody Treatment ◽  
Fungal Burden ◽  
Upstream Kinase

Masking the immunogenic cell wall epitope ß(1,3)-glucan under an outer layer of mannosylated glycoproteins is an important virulence factor deployed by Candida albicans during infection. Consequently, increased ß(1,3)-glucan exposure (unmasking) reveals C. albicans to the host’s immune system and attenuates its virulence. We have previously shown that activation of the Cek1 MAPK pathway via expression of a hyperactive allele of an upstream kinase (STE11ΔN467) induces unmasking. It also increased survival of mice in a murine disseminated candidiasis model and attenuated kidney fungal burden by ≥33 fold. In this communication, we utilized cyclophosphamide-induced immunosuppression to test if the clearance of the unmasked STE11ΔN467 mutant was dependent on the host immune system. Suppression of the immune response by cyclophosphamide reduced the attenuation in fungal burden caused by the STE11ΔN467 allele. Moreover, specific depletion of neutrophils via 1A8 antibody treatment also reduced STE11ΔN467-dependent fungal burden attenuation, but to a lesser extent than cyclophosphamide, demonstrating an important role for neutrophils in mediating fungal clearance of unmasked STE11ΔN467 cells. In an effort to understand the mechanism by which Ste11ΔN467 causes unmasking, transcriptomics were used to reveal that several components in the Cek1 MAPK pathway were upregulated, including the transcription factor CPH1 and the cell wall sensor DFI1. In this report we show that a cph1ΔΔ mutation restored ß(1,3)-glucan exposure to wild-type levels in the STE11ΔN467 strain, confirming that Cph1 is the transcription factor mediating Ste11ΔN467-induced unmasking. Furthermore, Cph1 is shown to induce a positive feedback loop that increases Cek1 activation. In addition, full unmasking by STE11ΔN467 is dependent on the upstream cell wall sensor DFI1. However, while deletion of DFI1 significantly reduced Ste11ΔN467-induced unmasking, it did not impact activation of the downstream kinase Cek1. Thus, it appears that once stimulated by Ste11ΔN467, Dfi1 activates a parallel signaling pathway that is involved in Ste11ΔN467-induced unmasking.

scholarly journals Iron alters the cell wall composition and intracellular lactate to affect Candida albicans susceptibility to antifungals and host immune response

2020 ◽  
Vol 295 (29) ◽  
pp. 10032-10044 ◽  
Author(s):  
Aparna Tripathi ◽  
Elisabetta Liverani ◽  
Alexander Y. Tsygankov ◽  
Sumant Puri
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Candida Albicans ◽  
Signaling Pathways ◽  
Host Immune Response ◽  
Fungal Cell Wall ◽  
Mitogen Activated Protein Kinase ◽  
Fungal Cell ◽  
High Iron ◽  
Cell Wall Architecture

Fungal pathogen Candida albicans has a complex cell wall consisting of an outer layer of mannans and an inner layer of β-glucans and chitin. The fungal cell wall is the primary target for antifungals and is recognized by host immune cells. Environmental conditions such as carbon sources, pH, temperature, and oxygen tension can modulate the fungal cell wall architecture. Cellular signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways, are responsible for sensing environmental cues and mediating cell wall alterations. Although iron has recently been shown to affect β-1,3-glucan exposure on the cell wall, we report here that iron changes the composition of all major C. albicans cell wall components. Specifically, high iron decreased the levels of mannans (including phosphomannans) and chitin; and increased β-1,3-glucan levels. These changes increased the resistance of C. albicans to cell wall-perturbing antifungals. Moreover, high iron cells exhibited adequate mitochondrial functioning; leading to a reduction in accumulation of lactate that signals through the transcription factor Crz1 to induce β-1,3-glucan masking in C. albicans. We show here that iron-induced changes in β-1,3-glucan exposure are lactate-dependent; and high iron causes β-1,3-glucan exposure by preventing lactate-induced, Crz1-mediated inhibition of activation of the fungal MAPK Cek1. Furthermore, despite exhibiting enhanced antifungal resistance, high iron C. albicans cells had reduced survival upon phagocytosis by macrophages. Our results underscore the role of iron as an environmental signal in multiple signaling pathways that alter cell wall architecture in C. albicans, thereby affecting its survival upon exposure to antifungals and host immune response.

scholarly journals Transcription Factor Efg1 Shows a Haploinsufficiency Phenotype in Modulating the Cell Wall Architecture and Immunogenicity of Candida albicans

2011 ◽  
Vol 11 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Martin Zavrel ◽  
Olivia Majer ◽  
Karl Kuchler ◽  
Steffen Rupp
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Structural Changes ◽  
Protein Composition ◽  
Surface Proteins ◽  
Wall Structure ◽  
Content Type ◽  
Cell Wall Biogenesis ◽  
General Metabolism

ABSTRACTTheCandida albicanstranscription factor Efg1 is known to be involved in many different cellular processes, including morphogenesis, general metabolism, and virulence. Here we show that besides its manifold roles, Efg1 also has a prominent effect on cell wall structure and composition, strongly affecting the structural glucan part. Deletion of only one allele ofEFG1already results in severe phenotypes for cell wall biogenesis, comparable to those with deletion of both alleles, indicative of a severe haploinsufficiency forEFG1. The observed defects in structural setup of the cell wall, together with previously reported alterations in expression of cell surface proteins, result in altered immunogenic properties of strains with compromised Efg1 function. This is shown by interaction studies with macrophages and primary dendritic cells. The structural changes in the cell wall carbohydrate meshwork presented here, together with the manifold changes in cell wall protein composition and metabolism reported in other studies, contribute to the altered immune response mounted by innate immune cells and to the altered virulence phenotypes observed for strains lackingEFG1.

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