scholarly journals Fungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses

2021 ◽  
Vol 7 (9) ◽  
pp. 739
Author(s):  
Chibuike Ibe ◽  
Carol A. Munro
Keyword(s):  
Cell Wall ◽  
Fungal Pathogens ◽  
Surface Coat ◽  
Cell Wall Proteins ◽  
Fungal Cell ◽  
Protein Coat ◽  
Cell Wall Remodeling ◽  
Wall Construction ◽  
And Function ◽  
Physical And Chemical

Candida species are part of the normal flora of humans, but once the immune system of the host is impaired and they escape from commensal niches, they shift from commensal to pathogen causing candidiasis. Candida albicans remains the primary cause of candidiasis, accounting for about 60% of the global candidiasis burden. The cell wall of C. albicans and related fungal pathogens forms the interface with the host, gives fungal cells their shape, and also provides protection against stresses. The cell wall is a dynamic organelle with great adaptive flexibility that allows remodeling, morphogenesis, and changes in its components in response to the environment. It is mainly composed of the inner polysaccharide rich layer (chitin, and β-glucan) and the outer protein coat (mannoproteins). The highly glycosylated protein coat mediates interactions between C. albicans cells and their environment, including reprograming of wall architecture in response to several conditions, such as carbon source, pH, high temperature, and morphogenesis. The mannoproteins are also associated with C. albicans adherence, drug resistance, and virulence. Vitally, the mannoproteins contribute to cell wall construction and especially cell wall remodeling when cells encounter physical and chemical stresses. This review describes the interconnected cell wall integrity (CWI) and stress-activated pathways (e.g., Hog1, Cek1, and Mkc1 mediated pathways) that regulates cell wall remodeling and the expression of some of the mannoproteins in C. albicans and other species. The mannoproteins of the surface coat is of great importance to pathogen survival, growth, and virulence, thus understanding their structure and function as well as regulatory mechanisms can pave the way for better management of candidiasis.

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.

scholarly journals Yeast Mnn9 is both a priming glycosyltransferase and an allosteric activator of mannan biosynthesis

Open Biology ◽  
2013 ◽  
Vol 3 (9) ◽  
pp. 130022 ◽  
Author(s):  
Alexander Striebeck ◽  
David A. Robinson ◽  
Alexander W. Schüttelkopf ◽  
Daan M. F. van Aalten
Keyword(s):  
Cell Wall ◽  
Fungal Pathogens ◽  
Enzyme Assay ◽  
Antibiotic Sensitivity ◽  
Site Directed Mutagenesis ◽  
Fungal Cell ◽  
Pol I ◽  
Conserved Amino Acids ◽  
Allosteric Activator ◽  
Mannan Synthesis

The fungal cell possesses an essential carbohydrate cell wall. The outer layer, mannan, is formed by mannoproteins carrying highly mannosylated O - and N -linked glycans. Yeast mannan biosynthesis is initiated by a Golgi-located complex (M-Pol I) of two GT-62 mannosyltransferases, Mnn9p and Van1p, that are conserved in fungal pathogens. Saccharomyces cerevisiae and Candida albicans mnn9 knockouts show an aberrant cell wall and increased antibiotic sensitivity, suggesting the enzyme is a potential drug target. Here, we present the structure of Sc Mnn9 in complex with GDP and Mn 2+ , defining the fold and catalytic machinery of the GT-62 family. Compared with distantly related GT-78/GT-15 enzymes, Sc Mnn9 carries an unusual extension. Using a novel enzyme assay and site-directed mutagenesis, we identify conserved amino acids essential for Sc Mnn9 ‘priming’ α-1,6-mannosyltransferase activity. Strikingly, both the presence of the Sc Mnn9 protein and its product, but not Sc Mnn9 catalytic activity, are required to activate subsequent Sc Van1 processive α-1,6-mannosyltransferase activity in the M-Pol I complex. These results reveal the molecular basis of mannan synthesis and will aid development of inhibitors targeting this process.

scholarly journals Inhibitors against Fungal Cell Wall Remodeling Enzymes

ChemMedChem ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. 128-132 ◽  
Author(s):  
Ignacio Delso ◽  
Jessika Valero-Gonzalez ◽  
Fernando Gomollón-Bel ◽  
Jorge Castro-López ◽  
Wenxia Fang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Cell Wall Remodeling

Interactions of proteins with other wall components: a pivotal step in fungal cell wall construction

1995 ◽  
Vol 73 (S1) ◽  
pp. 384-387 ◽  
Author(s):  
R. Sentandreu ◽  
M. Sentandreu ◽  
M. V. Elorza ◽  
M. Iranzo ◽  
S. Mormeneo
Keyword(s):  
Cell Wall ◽  
Protein Interactions ◽  
Cell Walls ◽  
Noncovalent Interactions ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Covalent Bonds ◽  
Viscoelastic Composite ◽  
Wall Construction ◽  
Wall Components

Following synthesis of its individual components, the cell wall of Candida albicans is assembled extracellularly in two steps. First, a viscoelastic composite is formed by noncovalent interactions between mannoproteins and other wall components. Second, the initial network is consolidated by formation of covalent cross-linkages among the wall polymers. In both processes, specific proteins may regulate the final yeast or mycelial morphology. These proteins might carry out part of what could be called a morphogenetic code. Experimental results have shown that some mannoproteins form supramolecular complexes. They are secreted independently, but released together from cell walls by hydrolases. In C. albicans cell walls a transglutaminase activity has been detected that could be responsible for the formation of covalent bonds between structural proteins. Key words: fungal cell wall, construction, morphogenesis, protein interactions, noncovalent linkages, covalent linkages.

scholarly journals Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens

2000 ◽  
Vol 44 (9) ◽  
pp. 2547-2548 ◽  
Author(s):  
David A. Stevens
Keyword(s):  
Cell Wall ◽  
Fungal Pathogens ◽  
Enzyme Inhibitors ◽  
Chitin Synthase ◽  
Synergistic Activity ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Nikkomycin Z ◽  
Synthase Inhibitor

ABSTRACT The interaction between inhibitors of components of the fungal cell wall, glucan and chitin, was studied in vitro with the respective synthase enzyme inhibitors LY 303366 and nikkomycin Z. WithAspergillus fumigatus synergy was noted for inhibition and killing, and synergistic activity was also noted for some isolates of other species presently regarded as difficult to treat.

scholarly journals The Fungal Cell Wall: Structure, Biosynthesis, and Function

2017 ◽  
pp. 267-292 ◽  
Author(s):  
Neil A. R. Gow ◽  
Jean-Paul Latge ◽  
Carol A. Munro
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Cell Wall Structure ◽  
Wall Structure ◽  
Fungal Cell ◽  
And Function
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