Biology subjects

Szymczak, S.

Publications and source records attributed to Szymczak, S..

3 recordsLinked to original sources

bioRxiv2023

Tryptophan wasting and disease activity as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases.

Chronic inflammatory diseases (CID) are systems disorders affecting various organs including the intestine, joint and skin. The essential amino acid tryptophan (Trp) is not only used for protein synthesis but can also be catabolized to various bioactive derivatives that are important for cellular energy metabolism and immune regulation. Increased Trp catabolism via the kynurenine pathway is seen across individual CID entities1-5. Here, we assessed the levels of Trp and tryptophan derivatives across 13 CID to investigate the extent and nature of Trp wasting as a systems phenomenon in CID. We found reduced serum Trp levels across the majority of CID and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Increases in the kynurenine-to-Trp ratio (Kyn:Trp) indicate that the kynurenine pathway is a major route for CID-related Trp wasting. However, the extent of Trp depletion and its relationship with disease activity varies by disease, indicating potential differences in Trp metabolism. In addition, we find that amino acid catabolism in chronic inflammation is specific to tryptophan wasting, whereas other proteinogenic amino acids are not affected. Hence, our results suggest that increased Trp catabolism is a common metabolic occurrence in CID that may directly affect systemic immunity. Grant supportThis work was supported by the DFG Cluster of Excellence 1261 "Precision medicine in chronic inflammation" (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund "Try-IBD" 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings ("Taxonomy, Treatments, Targets and Remission", No. 831434, "ImmUniverse", grant agreement No. 853995, "BIOMAP", grant agreement No. 821511).

immunology↗

bioRxiv2023

A single base pair duplication in SLC33A1 gene causes fetal losses and neonatal lethality in Manech Tete Rousse dairy sheep

Recently, we evidenced that the Manech Tete Rousse (MTR) deficient homozygous haplotype 2 (MTRDHH2) was likely to harbor a recessive lethal variant in ovine. In the present study, we fine mapped this region by analyzing the whole genome sequence of five MTRDHH2 heterozygous carriers compared to 95 sequences of non-carrier animals from MTR and others ovine breeds. We successfully identified a single base pair duplication in the SLC33A1 gene, resulting in a frameshift leading to a premature stop codon (p.Arg246Alafs*3). SLC33A1 acts as a transmembrane transporter of acetyl-Coenzyme A, essential for cellular metabolism. In order to assess for the lethal phenotype in homozygous MTR sheep, we generated at-risk matings by artificial insemination (AI) between rams and ewes heterozygous for the SLC33A1 variant named SLC33A1_dupG. Gestation status was checked 15 days post-AI by a molecular test from blood expression of the interferon Tau-stimulated MX1 gene, and by ultrasonography performed between 45 days and 60 days post-AI. Based on ultrasonography, the AI success was reduced by 12% compared to safe matings suggesting embryonic/fetal losses further confirmed by the molecular test based on MX1 differential expression. Forty-nine lambs were born from at-risk matings with a mortality rate of 34.7% observed before weaning. Homozygous SLC33A1_dupG lambs contributed to 47% of this mortality occurring mainly in the first five days after lambing with no obvious clinical signs. Thus, an appropriate management of SLC33A1_dupG (allele frequency of 0.04) in the MTR selection scheme should increase the overall fertility and lamb survival.

genomics↗

bioRxiv2019

Hemibiotrophic fungal pathogen induces systemic susceptibility and systemic shifts in wheat metabolome and microbiome composition

Yield losses caused by fungal pathogens represent a major threat to global food production. One of the most devastating fungal wheat pathogens is Zymoseptoria tritici. Despite the importance of this fungus and wheat as main staple food crop the underlying mechanisms of plant-pathogen interactions are poorly understood. Here we present a conceptual framework based on coinfection assays, comparative metabolomics, and microbiome profiling to study the interaction of Z. tritici in susceptible and resistant wheat. We demonstrate that Z. tritici suppresses the production of immune-related metabolites in a susceptible cultivar. Remarkably, this fungus-induced immune suppression spreads within the leaf and even to other leaves, a previously undescribed phenomenon that we term \"systemic induced susceptibility\". Using a comparative metabolomics approach, we identified defense-related biosynthetic pathways that are suppressed and induced in susceptible and resistant cultivars, respectively. We show that these fungus-induced changes also dramatically affect the wheat leaf microbiome. Our findings emphasize that immune suppression by this hemibiotrophic pathogen impacts specialized plant metabolism, alters its associated microbial communities, and renders wheat vulnerable to further infections.

plant biology↗