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 The Cek1 and Hog1 Mitogen-Activated Protein Kinases Play Complementary Roles in Cell Wall Biogenesis and Chlamydospore Formation in the Fungal Pathogen Candida albicans

2006 ◽  
Vol 5 (2) ◽  
pp. 347-358 ◽  
Author(s):  
B. Eisman ◽  
R. Alonso-Monge ◽  
E. Román ◽  
D. Arana ◽  
C. Nombela ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Map Kinase ◽  
Fungal Pathogen ◽  
Hog Pathway ◽  
Cell Wall Biogenesis ◽  
Chlamydospore Formation ◽  
Mitogen Activated Protein ◽  
Morphological Transitions ◽  
Relationship Of

ABSTRACT The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.

The Candida albicans pH-regulated KER1 gene encodes a lysine/glutamic-acid-rich plasma-membrane protein that is involved in cell aggregation

Microbiology ◽  
2004 ◽  
Vol 150 (8) ◽  
pp. 2641-2651 ◽  
Author(s):  
Amparo Galán ◽  
Manuel Casanova ◽  
Amelia Murgui ◽  
Donna M. MacCallum ◽  
Frank C. Odds ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Plasma Membrane ◽  
Glutamic Acid ◽  
Germ Tube ◽  
Cell Surface Hydrophobicity ◽  
Cell Aggregation ◽  
Surface Hydrophobicity ◽  
Amino Acid Sequences ◽  
Calcofluor White

Immunoscreening of a Candida albicans cDNA library with a polyclonal germ-tube-specific antibody (pAb anti-gt) resulted in the isolation of a gene encoding a lysine/glutamic-acid-rich protein, which was consequently designated KER1. The nucleotide and deduced amino acid sequences of this gene displayed no significant homology with any other known sequence. KER1 encodes a 134 kDa lysine (14·5 %)/glutamic acid (16·7 %) protein (Ker1p) that contains two potential transmembrane segments. KER1 was expressed in a pH-conditional manner, with maximal expression at alkaline pH and lower expression at pH 4·0, and was regulated by RIM101. A Δker1/Δker1 null mutant grew normally but was hyperflocculant under germ-tube-inducing conditions, yet this behaviour was also observed in stationary-phase cells grown under other incubation conditions. Western blotting analysis of different subcellular fractions, using as a probe a monospecific polyclonal antibody raised against a highly antigenic domain of Ker1p (pAb anti-Ker1p), revealed the presence of a 134 kDa band in the purified plasma-membrane fraction from the wild-type strain that was absent in the homologous preparation from Δker1/Δker1 mutant. The pattern of cell-wall protein and mannoprotein species released by digestion with β-glucanases, reactive towards pAbs anti-gt and anti-Ker1p, as well as against concanavalin A, was also different in the Δker1/Δker1 mutant. Mutant strains also displayed an increased cell-surface hydrophobicity and sensitivity to Congo red and Calcofluor white. Overall, these findings indicate that the mutant strain was affected in cell-wall composition and/or structure. The fact that the ker1 mutant had attenuated virulence in systemic mouse infections suggests that this surface protein is also important in host–fungus interactions.

scholarly journals The flowering hormone florigen accelerates secondary cell wall biogenesis to harmonize vascular maturation with reproductive development

2019 ◽  
Vol 116 (32) ◽  
pp. 16127-16136 ◽  
Author(s):  
Akiva Shalit-Kaneh ◽  
Tamar Eviatar-Ribak ◽  
Guy Horev ◽  
Naomi Suss ◽  
Roni Aloni ◽  
...  
Keyword(s):  
Cell Wall ◽  
Secondary Cell Wall ◽  
Floral Induction ◽  
Radial Expansion ◽  
Developmental Needs ◽  
Cellular Processes ◽  
Cell Wall Biogenesis ◽  
Reproductive Phase ◽  
Shoot System ◽  
Vascular Maturation

Florigen, a proteinaceous hormone, functions as a universal long-range promoter of flowering and concurrently as a generic growth-attenuating hormone across leaf and stem meristems. In flowering plants, the transition from the vegetative phase to the reproductive phase entails the orchestration of new growth coordinates and a global redistribution of resources, signals, and mechanical loads among organs. However, the ultimate cellular processes governing the adaptation of the shoot system to reproduction remain unknown. We hypothesized that if the mechanism for floral induction is universal, then the cellular metabolic mechanisms underlying the conditioning of the shoot system for reproduction would also be universal and may be best regulated by florigen itself. To understand the cellular basis for the vegetative functions of florigen, we explored the radial expansion of tomato stems. RNA-Seq and complementary genetic and histological studies revealed that florigen of endogenous, mobile, or induced origins accelerates the transcription network navigating secondary cell wall biogenesis as a unit, promoting vascular maturation and thereby adapting the shoot system to the developmental needs of the ensuing reproductive phase it had originally set into motion. We then demonstrated that a remarkably stable and broadly distributed florigen promotes MADS and MIF genes, which in turn regulate the rate of vascular maturation and radial expansion of stems irrespective of flowering or florigen level. The dual acceleration of flowering and vascular maturation by florigen provides a paradigm for coordinated regulation of independent global developmental programs.

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 Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase

2015 ◽  
Vol 112 (35) ◽  
pp. 11048-11053 ◽  
Author(s):  
Maya A. Farha ◽  
Tomasz L. Czarny ◽  
Cullen L. Myers ◽  
Liam J. Worrall ◽  
Shawn French ◽  
...  
Keyword(s):  
Cell Wall ◽  
High Throughput ◽  
High Throughput Screening ◽  
Teichoic Acid ◽  
Antibacterial Drug ◽  
Wall Teichoic Acid ◽  
Chemical Screening ◽  
Cellular Processes ◽  
Cell Wall Biogenesis ◽  
Antagonistic Interactions

Drug combinations are valuable tools for studying biological systems. Although much attention has been given to synergistic interactions in revealing connections between cellular processes, antagonistic interactions can also have tremendous value in elucidating genetic networks and mechanisms of drug action. Here, we exploit the power of antagonism in a high-throughput screen for molecules that suppress the activity of targocil, an inhibitor of the wall teichoic acid (WTA) flippase in Staphylococcus aureus. Well-characterized antagonism within the WTA biosynthetic pathway indicated that early steps would be sensitive to this screen; however, broader interactions with cell wall biogenesis components suggested that it might capture additional targets. A chemical screening effort using this approach identified clomiphene, a widely used fertility drug, as one such compound. Mechanistic characterization revealed the target was the undecaprenyl diphosphate synthase, an enzyme that catalyzes the synthesis of a polyisoprenoid essential for both peptidoglycan and WTA synthesis. The work sheds light on mechanisms contributing to the observed suppressive interactions of clomiphene and in turn reveals aspects of the biology that underlie cell wall synthesis in S. aureus. Further, this effort highlights the utility of antagonistic interactions both in high-throughput screening and in compound mode of action studies. Importantly, clomiphene represents a lead for antibacterial drug discovery.

scholarly journals Curcumin Targets Cell Wall Integrity via Calcineurin-Mediated Signaling in Candida albicans

2013 ◽  
Vol 58 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Awanish Kumar ◽  
Sanjiveeni Dhamgaye ◽  
Indresh Kumar Maurya ◽  
Ashutosh Singh ◽  
Monika Sharma ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Critical Role ◽  
Pathogenic Fungi ◽  
Cell Wall Integrity ◽  
Ergosterol Biosynthesis ◽  
Ros Generation ◽  
Calcofluor White ◽  
Content Type ◽  
Cell Wall Damage

ABSTRACTCurcumin (CUR) shows antifungal activity against a range of pathogenic fungi, includingCandida albicans. The reported mechanisms of action of CUR include reactive oxygen species (ROS) generation, defects in the ergosterol biosynthesis pathway, decrease in hyphal development, and modulation of multidrug efflux pumps. Reportedly, each of these pathways is independently linked to the cell wall machinery inC. albicans, but surprisingly, CUR has not been previously implicated in cell wall damage. In the present study, we performed transcriptional profiling to identify the yet-unidentified targets of CUR inC. albicans. We found that, among 348 CUR-affected genes, 51 were upregulated and 297 were downregulated. Interestingly, most of the cell wall integrity pathway genes were downregulated. The possibility of the cell wall playing a critical role in the mechanism of CUR required further validation; therefore, we performed specific experiments to establish if there was any link between the two. The fractional inhibitory concentration index values of 0.24 to 0.37 show that CUR interacts synergistically with cell wall-perturbing (CWP) agents (caspofungin, calcofluor white, Congo red, and SDS). Furthermore, we could observe cell wall damage and membrane permeabilization by CUR alone, as well as synergistically with CWP agents. We also found hypersusceptibility in calcineurin and mitogen-activated protein (MAP) kinase pathway mutants against CUR, which confirmed that CUR also targets cell wall biosynthesis inC. albicans. Together, these data provide strong evidence that CUR disrupts cell wall integrity inC. albicans. This new information on the mechanistic action of CUR could be employed in improving treatment strategies and in combinatorial drug therapy.

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 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.

scholarly journals The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for cell wall integrity

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 2004-2020 ◽  
Author(s):  
Emilia Moreno-Ruiz ◽  
Giuseppe Ortu ◽  
Piet W. J. de Groot ◽  
Fabien Cottier ◽  
Céline Loussert ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Pathogens ◽  
High Sensitivity ◽  
Wall Structure ◽  
Minor Role ◽  
Cell Wall Proteins ◽  
Calcofluor White ◽  
Fungal Cell ◽  
A Minor

The fungal cell wall is essential in maintaining cellular integrity and plays key roles in the interplay between fungal pathogens and their hosts. The PGA59 and PGA62 genes encode two short and related glycosylphosphatidylinositol-anchored cell wall proteins and their expression has been previously shown to be strongly upregulated when the human pathogen Candida albicans grows as biofilms. Using GFP fusion proteins, we have shown that Pga59 and Pga62 are cell-wall-located, N- and O-glycosylated proteins. The characterization of C. albicans pga59Δ/pga59Δ, pga62Δ/pga62Δ and pga59Δ/pga59Δ pga62Δ/pga62Δ mutants suggested a minor role of these two proteins in hyphal morphogenesis and that they are not critical to biofilm formation. Importantly, the sensitivity to different cell-wall-perturbing agents was altered in these mutants. In particular, simultaneous inactivation of PGA59 and PGA62 resulted in high sensitivity to Calcofluor white, Congo red and nikkomicin Z and in resistance to caspofungin. Furthermore, cell wall composition and observation by transmission electron microscopy indicated an altered cell wall structure in the mutant strains. Collectively, these data suggest that the cell wall proteins Pga59 and Pga62 contribute to cell wall stability and structure.

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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