Dataset Information

Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.

ABSTRACT: Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, and even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response to infection via local tryptophan deprivation, active catabolite production, and non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiology is unclear. Here, we show that Aspergillus fumigatus possesses three ido genes that are expressed under conditions of hypoxia or tryptophan abundance. Loss of these genes results in increased fungal pathogenicity and inflammation in a mouse model of aspergillosis, driven by an alternative tryptophan degradation pathway to indole derivatives and the host aryl hydrocarbon receptor. Fungal tryptophan metabolic pathways thus cooperate with the host xenobiotic response to shape host-microbe interactions in local tissue microenvironments.

SUBMITTER: Zelante T

PROVIDER: S-EPMC7844877 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.

Zelante Teresa T Choera Tsokyi T Beauvais Anne A Fallarino Francesca F Paolicelli Giuseppe G Pieraccini Giuseppe G Pieroni Marco M Galosi Claudia C Beato Claudia C De Luca Antonella A Boscaro Francesca F Romoli Riccardo R Liu Xin X Warris Adilia A Verweij Paul E PE Ballard Eloise E Borghi Monica M Pariano Marilena M Costantino Gabriele G Calvitti Mario M Vacca Carmine C Oikonomou Vasilis V Gargaro Marco M Wong Alicia Yoke Wei AYW Boon Louis L den Hartog Marcel M Spáčil Zdeněk Z Puccetti Paolo P Latgè Jean-Paul JP Keller Nancy P NP Romani Luigina L

Cell reports 20210101 4

Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, and even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response to infection via local tryptophan deprivation, active catabolite production, and non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiolog ...[more]

PMID: 33503414

Similar Datasets

Project description:Invasive aspergillosis (IA) is a life-threatening infectious disease caused by fungi from the genus Aspergillus, with an associated mortality as high as 90% in certain populations. IA-associated pulmonary lesions are characteristically depleted in oxygen relative to normal lung tissue, and it has been shown that the most common causal agent of IA, Aspergillus fumigatus, must respond to low-oxygen environments for pathogenesis and disease progression. Previous studies have demonstrated marked alterations to the Aspergillus fumigatus transcriptome in response to low-oxygen environments that induce a 'hypoxia response'. Consequently, we hypothesized that these transcriptomic changes would alter the volatile metabolome and generate a volatile hypoxia signature. In the present study, we analyzed the volatile molecules produced by A. fumigatus in both oxygen replete (normoxia) and depleted (hypoxia) environments via headspace solid-phase micro-extraction coupled to two-dimensional gas chromatography-time-of-flight mass spectrometry. Using the machine learning algorithm random forest, we identified 19 volatile molecules that were discriminatory between the four growth conditions assessed in this study (i.e., early hypoxia (1 h), late hypoxia (8 h), early normoxia (1 h), and late normoxia (8 h)), as well as a set of 19 that were discriminatory between late hypoxia cultures and all other growth conditions in aggregate. Nine molecules were common to both comparisons, while the remaining 20 were specific to only one of two. We assigned putative identifications to 13 molecules, of which six were most highly abundant in late hypoxia cultures. Previously acquired transcriptomic data identified putative biochemical pathways induced in hypoxia conditions that plausibly account for the production of a subset of these molecules, including 2,3-butanedione and 3-hydroxy-2-butanone. These two molecules may represent a novel hypoxia fitness pathway in A. fumigatus, and could be useful in the detection of hypoxia-associated A. fumigatus lesions that develop in established IA infections.

Dataset Information

Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.

Publications

Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets