scholarly journals Requirement for Candida albicans Sun41 in Biofilm Formation and Virulence

2007 ◽  
Vol 6 (11) ◽  
pp. 2046-2055 ◽  
Author(s):  
Carmelle T. Norice ◽  
Frank J. Smith ◽  
Norma Solis ◽  
Scott G. Filler ◽  
Aaron P. Mitchell
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Insertional Mutagenesis ◽  
Surface Protein ◽  
Altered Expression ◽  
Promising Therapeutic Target ◽  
A Cell ◽  
Homozygous Mutations ◽  
Insertion Mutations

ABSTRACT The cell wall of Candida albicans lies at the crossroads of pathogenicity and therapeutics. It contributes to pathogenicity through adherence and invasion; it is the target of both chemical and immunological antifungal strategies. We have initiated a dissection of cell wall function through targeted insertional mutagenesis of cell wall-related genes. Among 25 such genes, we were unable to generate homozygous mutations in 4, and they may be essential for viability. We created homozygous mutations in the remaining 21 genes. Insertion mutations in SUN41, Orf19.5412, Orf19.1277, MSB2, Orf19.3869, and WSC1 caused hypersensitivity to the cell wall inhibitor caspofungin, while two different ecm33 insertions caused mild caspofungin resistance. Insertion mutations in SUN41 and Orf19.5412 caused biofilm defects. Through analysis of homozygous sun41Δ/sun41Δ deletion mutants and sun41Δ/sun41Δ+pSUN41-complemented strains, we verified that Sun41 is required for biofilm formation and normal caspofungin tolerance. The sun41Δ/sun41Δ mutant had altered expression of four cell wall damage response genes, thus suggesting that it suffers a cell wall structural defect. Sun41 is required for inducing disease, because the mutant was severely attenuated in mouse models of disseminated and oropharyngeal candidiasis. Although the mutant produced aberrant hyphae, it had no defect in damaging endothelial or epithelial cells, unlike many other hypha-defective mutants. We suggest that the sun41Δ/sun41Δ cell wall defect is the primary cause of its attenuated virulence. As a small fungal surface protein with predicted glucosidase activity, Sun41 represents a promising therapeutic target.

scholarly journals Environmentally contingent control of Candida albicans cell wall integrity by transcriptional regulator Cup9

Genetics ◽  
2021 ◽  
Author(s):  
Yuichi Ichikawa ◽  
Vincent M Bruno ◽  
Carol A Woolford ◽  
Hannah Kim ◽  
Eunsoo Do ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Surface Protein ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Cell Wall Integrity ◽  
Yeast Growth ◽  
Transcription Factor Genes ◽  
A Cell ◽  
Rna Levels

Abstract The fungal pathogen Candida albicans is surrounded by a cell wall that is the target of caspofungin and other echinocandin antifungals. C. albicans can grow in several morphological forms, notably budding yeast and hyphae. Yeast and hyphal forms differ in cell wall composition, leading us to hypothesize that there may be distinct genes required for yeast and hyphal responses to caspofungin. Mutants in 27 genes reported previously to be caspofungin hypersensitive under yeast growth conditions were all caspofungin hypersensitive under hyphal growth conditions as well. However, a screen of mutants defective in transcription factor genes revealed that Cup9 is required for normal caspofungin tolerance under hyphal and not yeast growth conditions. In a hyphal-defective efg1Δ/Δ background, Cup9 is still required for normal caspofungin tolerance. This result argues that Cup9 function is related to growth conditions rather than cell morphology. RNA-seq conducted under hyphal growth conditions indicated that 361 genes were up-regulated and 145 genes were down-regulated in response to caspofungin treatment. Both classes of caspofungin-responsive genes were enriched for cell wall-related proteins, as expected for a response to disruption of cell wall integrity and biosynthesis. The cup9Δ/Δ mutant, treated with caspofungin, had reduced RNA levels of 40 caspofungin up-regulated genes, and had increased RNA levels of 8 caspofungin down-regulated genes, an indication that Cup9 has a narrow rather than global role in the cell wall integrity response. Five Cup9-activated surface-protein genes have roles in cell wall integrity, based on mutant analysis published previously (PGA31, IFF11) or shown here (ORF19.3499, ORF19.851 or PGA28), and therefore may explain the hypersensitivity of the cup9Δ/Δ mutant to caspofungin. Our findings define Cup9 as a new determinant of caspofungin susceptibility.

scholarly journals Candida albicans Sun41p, a Putative Glycosidase, Is Involved in Morphogenesis, Cell Wall Biogenesis, and Biofilm Formation

2007 ◽  
Vol 6 (11) ◽  
pp. 2056-2065 ◽  
Author(s):  
Ekkehard Hiller ◽  
Sonja Heine ◽  
Herwig Brunner ◽  
Steffen Rupp
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Cell Monolayer ◽  
The Sun ◽  
Calcofluor White ◽  
Cellular Processes ◽  
Cell Wall Biogenesis ◽  
Reduced Adherence ◽  
Higher Sensitivity

ABSTRACT The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis. In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the host-pathogen interaction.

scholarly journals Critical role for CaFEN1 and CaFEN12 of Candida albicans in cell wall integrity and biofilm formation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Md. Alfatah ◽  
Vinay K. Bari ◽  
Anubhav S. Nahar ◽  
Swati Bijlani ◽  
K. Ganesan
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Critical Role ◽  
Cell Wall Integrity

scholarly journals The Enterococcal Surface Protein, Esp, Is Involved in Enterococcus faecalis Biofilm Formation

2001 ◽  
Vol 67 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
Alejandro Toledo-Arana ◽  
Jaione Valle ◽  
Cristina Solano ◽  
Marı́a Jesús Arrizubieta ◽  
Carme Cucarella ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Biofilm Formation ◽  
Insertional Mutagenesis ◽  
Surface Protein ◽  
Structural Similarity ◽  
Abiotic Surfaces ◽  
Polyvinyl Chloride Plastic ◽  
Primary Attachment ◽  
Encoding Gene ◽  
The Relationship

ABSTRACT The enterococcal surface protein, Esp, is a high-molecular-weight surface protein of unknown function whose frequency is significantly increased among infection-derived Enterococcus faecalisisolates. In this work, a global structural similarity was found between Bap, a biofilm-associated protein of Staphylococcus aureus, and Esp. Analysis of the relationship between the presence of the Esp-encoding gene (esp) and the biofilm formation capacity in E. faecalis demonstrated that the presence of the esp gene is highly associated (P < 0.0001) with the capacity of E. faecalis to form a biofilm on a polystyrene surface, since 93.5% of the E. faecalis esp-positive isolates were capable of forming a biofilm. Moreover, none of the E. faecalis esp-deficient isolates were biofilm producers. Depending on theE. faecalis isolate, insertional mutagenesis ofesp caused either a complete loss of the biofilm formation phenotype or no apparent phenotypic defect. Complementation studies revealed that Esp expression in an E. faecalis esp-deficient strain promoted primary attachment and biofilm formation on polystyrene and polyvinyl chloride plastic from urine collection bags. Together, these results demonstrate that (i) biofilm formation capacity is widespread among clinical E. faecalis isolates, (ii) the biofilm formation capacity is restricted to the E. faecalis strains harboringesp, and (iii) Esp promotes primary attachment and biofilm formation of E. faecalis on abiotic surfaces.

scholarly journals Hwp1 and Related Adhesins Contribute to both Mating and Biofilm Formation in Candida albicans

2009 ◽  
Vol 8 (12) ◽  
pp. 1909-1913 ◽  
Author(s):  
Iuliana V. Ene ◽  
Richard J. Bennett
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Sexual Differentiation ◽  
Biofilm Formation ◽  
Filamentous Growth ◽  
Cell Wall Proteins ◽  
Related Cell

ABSTRACT Candida albicans Hwp1, Hwp2, and Rbt1 are related cell wall proteins expressed during the programs of sexual differentiation and filamentous growth. In this study, we compare strains lacking either single factors or a combination of these genes, and we demonstrate distinct but overlapping roles in mating and biofilm formation.

scholarly journals RBR1, a Novel pH-Regulated Cell Wall Gene of Candida albicans, Is Repressed by RIM101 and Activated by NRG1

2004 ◽  
Vol 3 (3) ◽  
pp. 776-784 ◽  
Author(s):  
Henrike Lotz ◽  
Kai Sohn ◽  
Herwig Brunner ◽  
Fritz A. Mühlschlegel ◽  
Steffen Rupp
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Transcriptional Profiling ◽  
Hyphal Growth ◽  
Additional Cell ◽  
A Cell ◽  
Acidic Conditions ◽  
Ph Dependent ◽  
Glycosylphosphatidyl Inositol

ABSTRACT The transcription factor Rim101p of Candida albicans has been shown to play a major role in pH-dependent gene regulation. Rim101p is involved in cell wall biosynthesis, since it regulates PHR1 and PHR2, two almost functionally redundant cell wall glycosidases important for adaptation to either neutral or acidic habitats within the human host. To identify additional cell wall components regulated by Rim101p, we performed transcriptional profiling with a cell wall-specific DNA microarray. We showed that Rim101p contributes to the activation of known hypha-specific genes such as HWP1 and RBT1 but is also required for repression of the previously uncharacterized potential cell wall genes RBR1, RBR2, and RBR3. Further characterization of RBR1 revealed that it encodes a small glycosylphosphatidyl inositol protein that is expressed under acidic conditions predominantly at low temperature. Deletion of the gene resulted in a filamentation defect at low pH. Most interestingly, NRG1, a transcriptional repressor of hyphal growth in C. albicans, was required for RBR1 expression. The apparently activating effect of NRG1 observed in this study has not been described before. In addition, we showed that expression of NRG1 is not only temperature but also pH dependent.

scholarly journals Function of Candida albicans Adhesin Hwp1 in Biofilm Formation

2006 ◽  
Vol 5 (10) ◽  
pp. 1604-1610 ◽  
Author(s):  
Clarissa J. Nobile ◽  
Jeniel E. Nett ◽  
David R. Andes ◽  
Aaron P. Mitchell
Keyword(s):  
Candida Albicans ◽  
Cell Surface ◽  
Biofilm Formation ◽  
Tight Binding ◽  
Surface Protein ◽  
Venous Catheter ◽  
Cell Surface Protein ◽  
Additional Support

ABSTRACT Hwp1 is a well-characterized Candida albicans cell surface protein, expressed only on hyphae, that mediates tight binding to oral epithelial cells. Prior studies indicate that HWP1 expression is dependent upon Bcr1, a key regulator of biofilm formation. Here we test the hypothesis that Hwp1 is required for biofilm formation. In an in vitro model, the hwp1/hwp1 mutant produces a thin biofilm that lacks much of the hyphal mass found in the hwp1/HWP1 reconstituted strain. In a biofilm cell retention assay, we find that the hwp1/hwp1 mutant is defective in retention of nonadherent bcr1/bcr1 mutant cells. In an in vivo rat venous catheter model, the hwp1/hwp1 mutant has a severe biofilm defect, yielding only yeast microcolonies in the catheter lumen. These properties of the hwp1/hwp1 mutant are consistent with its role as a hypha-specific adhesin and indicate that it is required for normal biofilm formation. Overexpression of HWP1 in a bcr1/bcr1 mutant background improves adherence in the in vivo catheter model. This finding provides additional support for the model that Hwp1 is critical for biofilm adhesion. Hwp1 is the first cell surface protein known to be required for C. albicans biofilm formation in vivo and is thus an excellent therapeutic target.

Characterisation of Pga1, a putative Candida albicans cell wall protein necessary for proper adhesion and biofilm formation

Mycoses ◽  
2010 ◽  
Vol 54 (6) ◽  
pp. 491-500 ◽  
Author(s):  
Rami Hashash ◽  
Samer Younes ◽  
Wael Bahnan ◽  
Joseph El Koussa ◽  
Katia Maalouf ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Cell Wall Protein
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