Deciphering cell wall integrity signalling in <i>Aspergillus fumigatus</i>: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases

Dichtl, Karl; Helmschrott, Christoph; Dirr, Franziska; Wagener, Johannes

doi:10.1111/j.1365-2958.2011.07946.x

Cited by 114 publications

(158 citation statements)

References 30 publications

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“…To further confirm that the metH gene is indispensable for A. fumigatus, we constructed a conditional expression strain, AfS180, in which the expression of the coding sequence is driven by a doxycycline-dependent Tet-ON module (see Fig. S7 in the supplemental material) (74,75), a system that has successfully been used in A. fumigatus to prove gene essentiality (76). In the presence of doxycycline, the metH gene is properly expressed to support growth of AfS180 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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e Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. Here, we have investigated sulfur (S) utilization by the human-pathogenic mold Aspergillus fumigatus during invasive growth. Our data reveal that inorganic S compounds or taurine is unlikely to serve as an S source during invasive pulmonary aspergillosis since a sulfate transporter mutant strain and a sulfite reductase mutant strain are fully virulent. In contrast, the S-containing amino acid cysteine is limiting for fungal growth, as proven by the reduced virulence of a cysteine auxotroph. Moreover, phenotypic characterization of this strain further revealed the robustness of the subordinate glutathione redox system. Interestingly, we demonstrate that methionine synthase is essential for A. fumigatus virulence, defining the biosynthetic route of this proteinogenic amino acid as a potential antifungal target. In conclusion, we provide novel insights into the nutritional requirements of A. fumigatus during pathogenesis, a prerequisite to understanding and fighting infection.

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Section: Resultsmentioning

confidence: 99%

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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“…Deletion of rho3 (rhoC) in A. fumigatus caused no discernible phenotypic changes, and deletion of rho2 and rho4 (rhoB and rhoD, respectively) are related to cell wall stress and integrity (651). In A. fumigatus, Rho1 seems to be essential, and deletion of rho2 and rho4 alters the cell wall integrity (655).…”

Section: Ras-gtpasesmentioning

confidence: 99%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

165

195

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SUMMARYThe genusTrichodermacontains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for “hot topic” research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism inT. reesei,T. atroviride, andT. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of eachTrichodermaspecies discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved inN-linked glycosylation was detected, as were indications for the ability ofTrichodermaspp. to generate hybrid galactose-containingN-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique toTrichoderma, and these warrant further investigation. We found interesting expansions in theTrichodermagenus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique toT. atrovirideis the duplication of the alternative sulfur amino acid synthesis pathway.

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“…MidA is specifically required for resistance to the chitin binding agents calcofluor white and Congo red. In addition, we have shown that the Rho GTPases Rho1, Rho2, and Rho4 play a role in CWI maintenance (14). However, the direct involvement of Rho1, Rho2, or Rho4 in the CWI signaling process of Aspergillus spp.…”

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confidence: 99%

Role of the Guanine Nucleotide Exchange Factor Rom2 in Cell Wall Integrity Maintenance of Aspergillus fumigatus

et al. 2013

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Aspergillus fumigatus is a mold and the causal agent of invasive aspergillosis, a systemic disease with high lethality. Recently, we identified and functionally characterized three stress sensors implicated in the cell wall integrity (CWI) signaling of this pathogen, namely, Wsc1, Wsc3, and MidA. Here, we functionally characterize Rom2, a guanine nucleotide exchange factor with essential function for the cell wall integrity of A. fumigatus. A conditional rom2 mutant has severe growth defects under repressive conditions and incorporates all phenotypes of the three cell wall integrity sensor mutants, e.g., the echinocandin sensitivity of the ⌬wsc1 mutant and the Congo red, calcofluor white, and heat sensitivity of the ⌬midA mutant. Rom2 interacts with Rho1 and shows a similar intracellular distribution focused at the hyphal tips. Our results place Rom2 between the cell surface stress sensors Wsc1, Wsc3, MidA, and Rho1 and their downstream effector mitogen-activated protein (MAP) kinase module Bck1-Mkk2-MpkA.

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Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases

Cited by 114 publications

References 30 publications

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Role of the Guanine Nucleotide Exchange Factor Rom2 in Cell Wall Integrity Maintenance of Aspergillus fumigatus

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