The fungal cell wall is located outside the plasma membrane and is the cell compartment that mediates all the relationships of the cell with the environment. It protects the contents of the cell, gives rigidity and defines the cellular structure. The cell wall is a skeleton with high plasticity that protects the cell from different stresses, among which osmotic changes stand out. The cell wall allows interaction with the external environment since some of its proteins are adhesins and receptors. Since, some components have a high immunogenic capacity, certain wall components can drive the host's immune response to promote fungus growth and dissemination. The cell wall is a characteristic structure of fungi and is composed mainly of glucans, chitin and glycoproteins. As the components of the fungal cell wall are not present in humans, this structure is an excellent target for antifungal therapy. In this article, we review recent data on the composition and synthesis, influence of the components of the cell wall in fungi-host interaction and the role as a target for the next generation of antifungal drugs in yeasts (Candida and Cryptococcus) and filamentous fungi (Aspergillus).

/pdf/the-fungal-cell-wall-candida-cryptococcus-and-aspergillus-54zl8aas5y.pdf

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species.

Cell wall glucans of fungi. A review.

https://research.birmingham.ac.uk/portal/files/48660822/Hopke_et_al_TIM_2018_accepted.pdf

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

The opportunistic fungal pathogen Aspergillus fumigatus is increasingly found as a coinfecting agent along with Pseudomonas aeruginosa in cystic fibrosis patients Amongst the numerous molecules secreted by P aeruginosa during its growth, phenazines constitute a major class P aeruginosa usually secreted four phenazines, pyocyanin (PYO), phenazine-1-carboxamide (PCN), 1-hydroxyphenazine (1-HP) and phenazine-1-carboxylic acid (PCA) These phenazines inhibited the growth of A fumigatus but the underlying mechanisms and the impact of these four phenazines on A fumigatus biology were not known In the present study, we analyzed the functions of the four phenazines and their mode of action on A fumigatus All four phenazines showed A fumigatus growth inhibitory effects by inducing production of reactive oxygen species (ROS), specifically O2·− and reactive nitrogen species (RNS), ONOO− A fumigatus Sod2p was the major factor involved in resistance against the ROS and RNS induced by phenazines Sub-inhibitory concentrations of PYO, PCA and PCN promote A fumigatus growth by an independent iron-uptake acquisition Of the four phenazines 1-HP had a redox-independent function; being able to chelate metal ions 1-HP induced A fumigatus iron starvation Our data show the fine-interactions existing between A fumigatus and P aeruginosa, which can lead to stimulatory or antagonistic effects

/pdf/pseudomonas-aeruginosa-manipulates-redox-and-iron-58qcdj913v.pdf

Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines.

α-(1,3)-Glucan is a major component of the cell wall of Aspergillus fumigatus, an opportunistic human fungal pathogen. There are three genes (AGS1, AGS2 and AGS3) controlling the biosynthesis of α-(1,3)-glucan in this fungal species. Deletion of all the three AGS genes resulted in a triple mutant that was devoid of α-(1,3)-glucan in its cell wall; however, its growth and germination was identical to that of the parental strain in vitro. In the experimental murine aspergillosis model, this mutant was less pathogenic than the parental strain. The AGS deletion resulted in an extensive structural modification of the conidial cell wall, especially conidial surface where the rodlet layer was covered by an amorphous glycoprotein matrix. This surface modification was responsible for viability reduction of conidia in vivo, which explains decrease in the virulence of triple agsΔ mutant.

/pdf/deletion-of-the-a-1-3-glucan-synthase-genes-induces-a-3og9yl1a20.pdf

Deletion of the α-(1,3)-glucan synthase genes induces a restructuring of the conidial cell wall responsible for the avirulence of Aspergillus fumigatus.

β-(1,3)-Glucan, the major fungal cell wall component, ramifies through β-(1,6)-glycosidic linkages, which facilitates its binding with other cell wall components contributing to proper cell wall assembly. Using Saccharomyces cerevisiae as a model, we developed a protocol to quantify β-(1,6)-branching on β-(1,3)-glucan. Permeabilized S. cerevisiae and radiolabeled substrate UDP-(14C)glucose allowed us to determine branching kinetics. A screening aimed at identifying deletion mutants with reduced branching among them revealed only two, the bgl2Δ and gas1Δ mutants, showing 15% and 70% reductions in the branching, respectively, compared to the wild-type strain. Interestingly, a recombinant Gas1p introduced β-(1,6)-branching on the β-(1,3)-oligomers following its β-(1,3)-elongase activity. Sequential elongation and branching activity of Gas1p occurred on linear β-(1,3)-oligomers as well as Bgl2p-catalyzed products [short β-(1,3)-oligomers linked by a linear β-(1,6)-linkage]. The double S. cerevisiae gas1Δ bgl2Δ mutant showed a drastically sick phenotype. An ScGas1p ortholog, Gel4p from Aspergillus fumigatus, also showed dual β-(1,3)-glucan elongating and branching activity. Both ScGas1p and A. fumigatus Gel4p sequences are endowed with a carbohydrate binding module (CBM), CBM43, which was required for the dual β-(1,3)-glucan elongating and branching activity. Our report unravels the β-(1,3)-glucan branching mechanism, a phenomenon occurring during construction of the cell wall which is essential for fungal life. IMPORTANCE The fungal cell wall is essential for growth, morphogenesis, protection, and survival. In spite of being essential, cell wall biogenesis, especially the core β-(1,3)-glucan ramification, is poorly understood; the ramified β-(1,3)-glucan interconnects other cell wall components. Once linear β-(1,3)-glucan is synthesized by plasma membrane-bound glucan synthase, the subsequent event is its branching event in the cell wall space. Using Saccharomyces cerevisiae as a model, we identified GH72 and GH17 family glycosyltransferases, Gas1p and Bgl2p, respectively, involved in the β-(1,3)-glucan branching. The sick phenotype of the double Scgas1Δ bgl2Δ mutant suggested that β-(1,3)-glucan branching is essential. In addition to ScGas1p, GH72 family ScGas2p and Aspergillus fumigatus Gel4p, having CBM43 in their sequences, showed dual β-(1,3)-glucan elongating and branching activity. Our report identifies the fungal cell wall β-(1,3)-glucan branching mechanism. The essentiality of β-(1,3)-glucan branching suggests that enzymes involved in the glucan branching could be exploited as antifungal targets.

https://journals.asm.org/doi/pdf/10.1128/mBio.00619-17

The Dual Activity Responsible for the Elongation and Branching of β-(1,3)-Glucan in the Fungal Cell Wall.

In vitro testing of Aspergillus fumigatus susceptibility to echinocandins has always been a challenge. Using a simple and quick colorimetric method to analyze the activity of inhibitors of β-1,3-glucan synthesis, we found that the composition of the culture medium significantly influences glucan synthesis and consequently the antifungal properties of inhibitors of β-1,3-glucan synthesis when they are tested alone or in combination with chitin synthase inhibitors.

https://hal-pasteur.archives-ouvertes.fr/pasteur-01725799/document

The composition of the culture medium influences the β-1,3-glucan metabolism of Aspergillus fumigatus and the antifungal activity of inhibitors of β-1,3-glucan synthesis

Synthesis -1,3-Glucan β Activity of Inhibitors of Aspergillus fumigatus and the Antifungal -1,3-Glucan Metabolism of β Influences the The Composition of the Culture Medium

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The Dual Activity Responsible for the Elongation and Branching of β-(1,3)-Glucan in the Fungal Cell Wall.

The composition of the culture medium influences the β-1,3-glucan metabolism of Aspergillus fumigatus and the antifungal activity of inhibitors of β-1,3-glucan synthesis

Synthesis -1,3-Glucan β Activity of Inhibitors of Aspergillus fumigatus and the Antifungal -1,3-Glucan Metabolism of β Influences the The Composition of the Culture Medium