scholarly journals Cooperative Role of MAPK Pathways in the Interaction of Candida albicans with the Host Epithelium

2019 ◽  
Vol 8 (1) ◽  
pp. 48 ◽  
Author(s):  
Inês Correia ◽  
Daniel Prieto ◽  
Elvira Román ◽  
Duncan Wilson ◽  
Bernhard Hube ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Epithelial Damage ◽  
Mapk Pathways ◽  
Molecular Approaches ◽  
Abiotic Surfaces ◽  
Solid Media ◽  
Epithelial Invasion ◽  
Semi Solid

Candida albicans is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control the expression of key virulence factors such as the yeast-to-hypha transition, the biogenesis of the cell wall, and the interaction with the host. In the present study, we have combined molecular approaches and infection biology to analyse the role of C. albicans MAPK pathways during an epithelial invasion. Hog1 was found to be important for adhesion to abiotic surfaces but was dispensable for damage to epithelial cells. The Mkc1 cell wall integrity (CWI) and Cek1 pathways, on the other hand, were both required for oral epithelial damage. Analysis of the ability to penetrate nutrient-rich semi-solid media revealed a cooperative role for Cek1 and Mkc1 in this process. Finally, cek2Δ (as well as cek1Δ) but not mkc1Δ or hog1Δ mutants, exhibited elevated β-glucan unmasking as revealed by immunofluorescence studies. Therefore, the four MAPK pathways play distinct roles in adhesion, epithelial damage, invasion and cell wall remodelling that may contribute to the pathogenicity of C. albicans.

scholarly journals Role of the Candida albicans MNN1 gene family in cell wall structure and virulence

2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Steven Bates ◽  
Rebecca A Hall ◽  
Jill Cheetham ◽  
Mihai G Netea ◽  
Donna M MacCallum ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Gene Family ◽  
Cell Wall Structure ◽  
Wall Structure

scholarly journals A Candida albicans cell wall-linked protein promotes invasive filamentation into semi-solid medium

2010 ◽  
Vol 76 (3) ◽  
pp. 733-748 ◽  
Author(s):  
Paola C. Zucchi ◽  
Talya R. Davis ◽  
Carol A. Kumamoto
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Solid Medium ◽  
Semi Solid

scholarly journals Mannan molecular sub-structures control nanoscale glucan exposure in Candida

2017 ◽  
Author(s):  
Matthew S. Graus ◽  
Michael J. Wester ◽  
Douglas W. Lowman ◽  
David L. Williams ◽  
Michael D. Kruppa ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Super Resolution ◽  
Ligand Interaction ◽  
Interaction Sites ◽  
Single Receptor ◽  
Labile N ◽  
Innate Immune Evasion ◽  
Acid Labile

AbstractN-linked mannans (N-mannans) in the cell wall of Candida albicans are thought to mask β-(1,3)-glucan from recognition by Dectin-1, contributing to innate immune evasion. Lateral cell wall exposures of glucan on Candida albicans are predominantly single receptor-ligand interaction sites and are restricted to nanoscale geometries. Candida species exhibit a range of basal glucan exposures and their mannans also vary in size and complexity at the molecular level. We used super resolution fluorescence imaging and a series of protein mannosylation mutants in C. albicans and C. glabrata to investigate the role of specific N-mannan features in regulating the nanoscale geometry of glucan exposure. Decreasing acid labile mannan abundance and α-(1,6)-mannan backbone length correlated most strongly with increased density and nanoscopic size of glucan exposures in C. albicans and C. glabrata, respectively. Additionally, a C. albicans clinical isolate with high glucan exposure produced similarly perturbed N-mannan structures and exhibited similar changes to nanoscopic glucan exposure geometry. We conclude that acid labile N-mannan controls glucan exposure geometry at the nanoscale. Furthermore, variations in glucan nanoexposure characteristics are clinically relevant and are likely to impact the nature of the pathogenic surface presented to innate immunocytes at dimensions relevant to receptor engagement, aggregation and signaling.

scholarly journals Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

2009 ◽  
Vol 8 (8) ◽  
pp. 1235-1249 ◽  
Author(s):  
Elvira Román ◽  
Fabien Cottier ◽  
Joachim F. Ernst ◽  
Jesús Pla
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Protein Kinase ◽  
Osmotic Shock ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
High Osmolarity ◽  
Cell Wall Biogenesis ◽  
Solid Media ◽  
Mitogen Activated Protein

ABSTRACT We have characterized the role that the Msb2 protein plays in the fungal pathogen Candida albicans by the use of mutants defective in the putative upstream components of the HOG pathway. Msb2, in cooperation with Sho1, controls the activation of the Cek1 mitogen-activated protein kinase under conditions that damage the cell wall, thus defining Msb2 as a signaling element of this pathway in the fungus. msb2 mutants display altered sensitivity to Congo red, caspofungin, zymolyase, or tunicamycin, indicating that this protein is involved in cell wall biogenesis. Msb2 (as well as Sho1 and Hst7) is involved in the transmission of the signal toward Cek1 mediated by the Cdc42 GTPase, as revealed by the use of activated alleles (Cdc42G12V) of this protein. msb2 mutants have a stronger defective invasion phenotype than sho1 mutants when tested on certain solid media that use mannitol or sucrose as a carbon source or under hypoxia. Interestingly, Msb2 contributes to growth under conditions of high osmolarity when both branches of the HOG pathway are altered, as triple ssk1 msb2 sho1 mutants (but not any single or double mutant) are osmosensitive. However, this phenomenon is independent of the presence of Hog1, as Hog1 phosphorylation, Hog1 translocation to the nucleus, and glycerol accumulation are not affected in this mutant following an osmotic shock. These results reveal essential functions in morphogenesis, invasion, cell wall biogenesis, and growth under conditions of high osmolarity for Msb2 in C. albicans and suggest the divergence and specialization of this signaling pathway in filamentous fungi.

The role of TNF-α in a murine model of Kawasaki disease arteritis induced with a Candida albicans cell wall polysaccharide

2013 ◽  
Vol 24 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Toshiaki Oharaseki ◽  
Yuki Yokouchi ◽  
Hitomi Yamada ◽  
Hiroshi Mamada ◽  
Satoshi Muto ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Kawasaki Disease ◽  
Murine Model ◽  
Cell Wall Polysaccharide ◽  
Tnf Α

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.

The role of TNF-α in a murine model of Kawasaki disease arteritis induced with a Candida albicans cell wall polysaccharide

2013 ◽  
Author(s):  
Toshiaki Oharaseki ◽  
Yuki Yokouchi ◽  
Hitomi Yamada ◽  
Hiroshi Mamada ◽  
Satoshi Muto ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Kawasaki Disease ◽  
Murine Model ◽  
Cell Wall Polysaccharide ◽  
Tnf Α

scholarly journals Candida albicans cell wall integrity transcription factors regulate polymicrobial biofilm formation with Streptococcus gordonii

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7870 ◽  
Author(s):  
Jennifer Chinnici ◽  
Lisa Yerke ◽  
Charlene Tsou ◽  
Sujay Busarajan ◽  
Ryan Mancuso ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Biofilm Formation ◽  
Mixed Cultures ◽  
Cell Wall Integrity ◽  
Antibiotic Tolerance ◽  
Streptococcus Gordonii ◽  
Knock Out

Polymicrobial biofilms play important roles in oral and systemic infections. The oral plaque bacterium Streptococcus gordonii is known to attach to the hyphal cell wall of the fungus Candida albicans to form corn-cob like structures in biofilms. However, the role of C. albicans in formation of polymicrobial biofilms is not completely understood. The objective of this study was to determine the role of C. albicans transcription factors in regulation of polymicrobial biofilms and antibiotic tolerance of S. gordonii. The proteins secreted by C. albicans and S. gordonii in mixed planktonic cultures were determined using mass spectrometry. Antibiotic tolerance of S. gordonii to ampicillin and erythromycin was determined in mixed cultures and mixed biofilms with C. albicans. Additionally, biofilm formation of S. gordonii with C. albicans knock-out mutants of 45 transcription factors that affect cell wall integrity, filamentous growth and biofilm formation was determined. Furthermore, these mutants were also screened for antibiotic tolerance in mixed biofilms with S. gordonii. Analysis of secreted proteomes resulted in the identification of proteins being secreted exclusively in mixed cultures. Antibiotic testing showed that S. gordonii had significantly increased survival in mixed planktonic cultures with antibiotics as compared to single cultures. C. albicans mutants of transcription factors Sfl2, Brg1, Leu3, Cas5, Cta4, Tec1, Tup1, Rim101 and Efg1 were significantly affected in mixed biofilm formation. Also mixed biofilms of S. gordonii with mutants of C. albicans transcription factors, Tec1 and Sfl2, had significantly reduced antibiotic tolerance as compared to control cultures. Our data indicates that C. albicans may have an important role in mixed biofilm formation as well as antibiotic tolerance of S. gordonii in polymicrobial biofilms. C. albicans may play a facilitating role than being just an innocent bystander in oral biofilms and infections.

scholarly journals PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion

Microbiology ◽  
2010 ◽  
Vol 156 (8) ◽  
pp. 2484-2494 ◽  
Author(s):  
Julia Calderon ◽  
Martin Zavrel ◽  
Enrico Ragni ◽  
William A. Fonzi ◽  
Steffen Rupp ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Crucial Role ◽  
Extracellular Enzymes ◽  
Hyphal Growth ◽  
Fungal Cell ◽  
Cell Monolayers ◽  
Cell Wall Assembly ◽  
Abiotic Surfaces ◽  
Wall Assembly

The fungal cell wall plays a crucial role in host–pathogen interactions. Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space. Candida albicans Phr1 and Phr2 proteins belong to family GH72 of the β-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly. PHR1 and PHR2, homologues of Saccharomyces cerevisiae GAS1, are differently regulated by extracellular pH. PHR1 is expressed when ambient pH is 5.5 or higher, whereas PHR2 has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence. In this work we explored whether PHR1 deletion affects the ability of C. albicans to adhere to and invade human epithelia. PHR1 null mutants exhibited a marked reduction in adhesion to both abiotic surfaces and epithelial cell monolayers. In addition, the mutant was unable to penetrate and invade reconstituted human epithelia. Transcription profiling of selected hyphal-specific and adhesin-encoding genes indicated that in the PHR1 null mutant, HWP1 and ECE1 transcript levels were similarly reduced in both adhesion and suspension conditions. These results, combined with microscopy analysis of the septum position, suggest that PHR1 is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth. Thus, the β-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in the maintenance of the morphological state on which the adhesive and invasive properties of C. albicans greatly depend.

scholarly journals Contribution of Phospholipomannan to the Surface Expression of β-1,2-Oligomannosides in Candida albicans and Its Presence in Cell Wall Extracts

2002 ◽  
Vol 70 (8) ◽  
pp. 4323-4328 ◽  
Author(s):  
D. Poulain ◽  
C. Slomianny ◽  
T. Jouault ◽  
J. M. Gomez ◽  
P. A. Trinel
Keyword(s):  
Cell Wall ◽  
Monoclonal Antibodies ◽  
Candida Albicans ◽  
Fluorescence Microscopy ◽  
Cell Surface ◽  
Western Blotting ◽  
Surface Expression ◽  
Solid Media ◽  
Protective Antibodies ◽  
Complex Expression

ABSTRACT β-1,2-Oligomannosides (β-1,2-Man) derived from Candida albicans mannan have been shown to act as adhesins and to induce protective antibodies. We used monoclonal antibodies specific for β-1,2-Man in electron, confocal, and fluorescence microscopy to study the surface expression of β-1,2-Man epitopes. These monoclonal antibodies were also used for Western blotting of cell surface extracts to study the nature of the molecules expressing the β-Man epitopes. Evidence was obtained for the contribution of a glycolipid, phospholipomannan (PLM), to the complex expression of β-1,2-Man epitopes at the cell wall surfaces of yeasts grown on solid media. PLM was present in intercellular matrixes of colonies grown on agar and was detected as a contaminant in mannan batches prepared by conventional methods.

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