Cell wall biogenesis in a double chitin synthase mutant (chsG−/chsE−) of Aspergillus fumigatus

Mellado, Emilia; Dubreucq, Guy; Mol, P. C.; Sarfati, J.; Paris, Sophie; Diaquin, Michel; Holden, David W.; Rodríguez-Tudela, Juan Luis; Latgé, Jean‐Paul

doi:10.1016/s1087-1845(02)00516-9

Cited by 83 publications

(63 citation statements)

References 47 publications

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“…It is possible that uge4 is expressed under conditions that were not tested; however, an alternative explanation is that uge4 is a product of gene duplication that could have served a purpose earlier in evolution but has now become silenced. Similar silent gene duplications have been reported in other cell wall-related genes in A. fumigatus (64,65). Interestingly, silencing of epimerases in Aspergillus species may play a role in virulence because in the nonpathogenic species A. nidulans, ugeB, the ortholog of A. fumigatus uge3, has been reported to be silent (55).…”

Section: Speciessupporting

confidence: 66%

Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides

Lee

Gravelat

Cerone

et al. 2014

Journal of Biological Chemistry

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Background:Aspergillus fumigatus produces two galactose-containing exopolysaccharides, galactomannan and galactosaminogalactan. Results: Galactosaminogalactan synthesis requires the UDP-glucose 4-epimerases, Uge5 and Uge3, whereas galactomannan synthesis requires Uge5 alone. Conclusion: Epimerases in A. fumigatus play both distinct and overlapping roles in exopolysaccharide synthesis. Significance: Uncovering the biosynthetic pathways of galactosaminogalactan will be crucial in developing therapeutics targeting this exopolysaccharide.

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Section: Speciessupporting

confidence: 66%

Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides

Lee

Gravelat

Cerone

et al. 2014

Journal of Biological Chemistry

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“…The filamentous fungi, like A. fumigatus and A. nidulans, have as many as eight chitin synthase genes, divided into separate classes, that are known to play different roles in the cell (reviewed in reference 9). For example, a double deletion of chsG (a class III chitin synthase) and chsE (a class V chitin synthase), or a deletion of chsE alone, leads to a hyphal phenotype very similar to that of the wild-type organism treated with nikkomycin Z in this study (e.g., large, swollen cells spaced intermittently among normal hyphal threads) (17). However, the inactivation of A. fumigatus chsD does not lead to any obvious phenotypic defects, even though total chitin levels were decreased by almost 20% (18).…”

Section: Discussionmentioning

confidence: 51%

Differential Effects of Inhibiting Chitin and 1,3-β- d -Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus

Fortwendel

Juvvadi

Pinchai

et al. 2009

Antimicrob Agents Chemother

132

135

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Aspergillus fumigatus must be able to properly form hyphae and maintain cell wall integrity in order to establish invasive disease. Ras proteins and calcineurin each have been implicated as having roles in these processes. Here, we further delineate the roles of calcineurin and Ras activity in cell wall biosynthesis and hyphal morphology using genetic and pharmacologic tools. Strains deleted for three genes encoding proteins of these pathways, rasA (the Ras protein), cnaA (calcineurin), or crzA (the zinc finger transcription factor downstream of calcineurin), all displayed decreased cell wall 1,3-␤-D-glucan content. Echinocandin treatment further decreased the levels of 1,3-␤-D-glucan for all strains tested yet also partially corrected the hyphal growth defect of the ⌬rasA strain. The inhibition of glucan synthesis caused an increase in chitin content for wild-type, dominant-active rasA, and ⌬rasA strains. However, this important compensatory response was diminished in the calcineurin pathway mutants (⌬cnaA and ⌬crzA). Taken together, our data suggest that the Ras and calcineurin pathways act in parallel to regulate cell wall formation and hyphal growth. Additionally, the calcineurin pathway elements cnaA and crzA play a major role in proper chitin and glucan incorporation into the A. fumigatus cell wall.

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“…Numerous examples of functional discrepancy for two gene products in spite of very similar sequences have been found among cell wall gene families both in yeast and in molds. In A. fumigatus chitin synthesis, disruption of the CHSE and CHSD genes resulted in a decrease in chitin content of the cell wall mutant, whereas disruption of the CHSG gene did not (20). In Saccharomyces cerevisiae, three genes encode FKS homologs.…”

Section: Discussionmentioning

confidence: 99%

Two α(1-3) Glucan Synthases with Different Functions in Aspergillus fumigatus

Beauvais

Maubon

Park³

et al. 2005

Appl Environ Microbiol

119

121

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␣(1-3) glucan is a main component of the Aspergillus fumigatus cell wall. In spite of its importance, synthesis of this amorphous polymer has not been investigated to date. Two genes in A. fumigatus, AGS1 and AGS2, are highly homologous to the AGS genes of Schizosaccharomyces pombe, which encode putative ␣(1-3) glucan synthases. The predicted Ags proteins of A. fumigatus have an estimated molecular mass of 270 kDa. AGS1 and AGS2 were disrupted in A. fumigatus. Both ⌬ags mutants have similar altered hyphal morphologies and reduced conidiation levels. Only ⌬ags1 presented a reduction in the ␣(1-3) glucan content of the cell wall. These results showed that Ags1p and Ags2p were functionally different. The cellular localization of the two proteins was in agreement with their different functions: Ags1p was localized at the periphery of the cell in connection with the cell wall, whereas Ags2p was intracellularly located. An original experimental model of invasive aspergillosis based on mixed infection and quantitative PCR was developed to analyze the virulence of A. fumigatus mutant and wild-type strains. Using this model, it was shown that the cell wall and morphogenesis defects of ⌬ags1 and ⌬ags2 were not associated with a reduction in virulence in either mutant. This result showed that a 50% reduction in the content of the cell wall ␣(1-3) glucan does not play a significant role in A. fumigatus pathogenicity.The fungal cell wall of Aspergillus fumigatus is mainly composed of polysaccharides that can be separated into two fractions, depending on their solubility in hot sodium hydroxide (7). The alkali-insoluble (AI) fraction constitutes the wall skeleton. It is composed of a branched ␤(1-3) glucan to which are attached chitin, ␤(1-3) and ␤(1-4) glucan, and galactomannan (7). The alkali-soluble (AS) fraction contains mainly ␣(1-3) glucans and galactomannan (1). Galactomannan has been shown to be associated with host immune reactions against A. fumigatus (18). In A. fumigatus, ␣(1-3) glucan is the major polysaccharide of the cell wall (40% [dry weight] of the cell wall) (7). The role of ␣(1-3) glucan in A. fumigatus pathogenicity has not been investigated, although its role in virulence has been demonstrated in Histoplasma capsulatum, Paracoccidioides brasiliensis, and Blastomyces dermatitidis. In these species, mutants with a reduction of ␣(1-3) glucan in their cell wall are avirulent (13,16,30). The construction of a mutant with a reduced amount of ␣(1-3) glucan in the cell wall of A. fumigatus and the study of its virulence in a mouse model are the aims of this paper.The synthesis of ␣(1-3) glucan has been studied only in Schizosaccharomyces pombe. In this fungal species, ␣(1-3) glucan synthesis is controlled by a single gene, AGS1 [for ␣(1-3) glucan synthase], which is an essential gene (12, 15). ␣(1-3) glucan synthesis is essential for correct cell wall morphogenesis, since the mutant ⌬ags1 with a reduced ␣(1-3) glucan in its cell wall shows a loss of cell polarity at restrictive temperatures (12,15).In this paper...

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Cell wall biogenesis in a double chitin synthase mutant (chsG−/chsE−) of Aspergillus fumigatus

Cited by 83 publications

References 47 publications

Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides

Overlapping and Distinct Roles of Aspergillus fumigatus UDP-glucose 4-Epimerases in Galactose Metabolism and the Synthesis of Galactose-containing Cell Wall Polysaccharides

Differential Effects of Inhibiting Chitin and 1,3-β- d -Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus

Two α(1-3) Glucan Synthases with Different Functions in Aspergillus fumigatus

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