Candida glabrata tryptophan‐based pigment production via the Ehrlich pathway

Brunke, Sascha; Seider, Katja; Almeida, Ricardo Sergio; Heyken, Antje; Fleck, Christian Benjamin; Brock, Matthias; Barz, Dagmar; Rupp, Steffen; Hube, Bernhard

doi:10.1111/j.1365-2958.2010.07052.x

Cited by 37Fungal and yeast genetics researchMicrobial Metabolism and ApplicationsAntifungal resistance and susceptibility

Candida glabrata tryptophan‐based pigment production via the Ehrlich pathway

Brunke, Sascha, Seider, Katja, Almeida, Ricardo Sergio, Heyken, Antje, Fleck, Christian Benjamin, Brock, Matthias, Barz, Dagmar, Rupp, Steffen +1 more·2010·Molecular Microbiology

DOI 10.1111/j.1365-2958.2010.07052.x

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Abstract

Pigments contribute to the pathogenicity of many fungi, mainly by protecting fungal cells from host defence activities. Here, we have dissected the biosynthetic pathway of a tryptophan-derived pigment of the human pathogen Candida glabrata, identified key genes involved in pigment production and have begun to elucidate the possible biological function of the pigment. Using transcriptional analyses and a transposon insertion library, we have identified genes associated with pigment production. Targeted deletion mutants revealed that the pigment is a by-product of the Ehrlich pathway of tryptophan degradation: a mutant lacking a tryptophan-upregulated aromatic aminotransferase (Aro8) displayed significantly reduced pigmentation and a recombinantly expressed version of this protein was sufficient for pigment production in vitro. Pigment production is tightly regulated as the synthesis is affected by the presence of alternative nitrogen sources, carbon sources, cyclic AMP and oxygen. Growth of C. glabrata on pigment inducing medium leads to an increased resistance to hydrogen peroxide, an effect which was not observed with a mutant defective in pigmentation. Furthermore, pigmented yeast cells had a higher survival rate when exposed to human neutrophils and caused increased damage in a monolayer model of human epithelia, indicating a possible role of pigmentation during interactions with host cells.

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Tryptophan-based pigment production aids in survival of ROS stress.
“Furthermore, tryptophan-based pigment production is also known to aid in survival of the ROS stress [89].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [89]
C. glabrata cells producing tryptophan-based pigment cause increased damage to human oral epithelial TR146 cells.
“However, C. glabrata cells producing tryptophan-based pigment have been reported to cause increased damage to human oral epithelial TR146 cells [89].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [89]
A pigment derived from tryptophan protects C. glabrata against neutrophil attack.
“Although a pigment derived from tryptophan is known to protect C. glabrata against the neutrophil attack [89], a detailed characterization of C. glabrata-neutrophil interaction is yet to be done.”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [89]

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Authors: Brunke, S., Seider, K., Almeida, R. S., Heyken, A., Fleck, C. B., Brock, M., Barz, D., Rupp, S., & Hube, B.
Affiliations: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
Jena University Hospital (DE)
Fraunhofer Institute for Interfacial Engineering and Biotechnology (DE)
Corresponding author: Hube, Bernhard
ORCID: Brunke, Sascha
Brock, Matthias
Rupp, Steffen
Hube, Bernhard
Venue: Molecular Microbiology
Publisher: Wiley
Published: 2010-03-29
Volume: 76
Issue: 1
Pages: 25-47
ISSN: 0950-382X (ISSN-L)
1365-2958
DOI: 10.1111/j.1365-2958.2010.07052.x
OpenAlex: W2117338697
Cited by: 37
References: 96
Citations by year: 2025: 3 · 2024: 3 · 2021: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 3
FWCI: 1.43
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Molecular Microbiology (publishedVersion)
PubMed (publishedVersion)
Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords: Candida glabrata, fungal pigmentation, tryptophan degradation, Ehrlich pathway, aromatic aminotransferase, pigment synthesis, hydrogen peroxide resistance, epithelial damage, host-pathogen interaction, fungal pathogenicity, transposon insertion library, deletion mutants
MeSH terms: Cyclic AMP, Carbon, Cells, Cultured, DNA Transposable Elements, Epithelial Cells, Genes, Fungal, Humans, Hydrogen Peroxide, Neutrophils, Nitrogen, Oxygen, Pigments, Biological, Tryptophan, Gene Expression Regulation, Fungal, Mutagenesis, Insertional, Gene Deletion, Gene Expression Profiling, Candida glabrata, Biosynthetic Pathways

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Candida glabrata tryptophan‐based pigment production via the Ehrlich pathway

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