Taxonomic group: fungi / Chytridiomycota
(Phylum: Chytridiomycota)
Host organism: Xenopus laevis
Associated disease: chytridiomycosis
NCBI PubMed ID: 26371122Publication DOI: 10.1128/IAI.00877-15Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: louise.rollins-smith
vanderbilt.edu
Institutions: Departments of Pathology, Microbiology and Immunology and of Pediatrics, Vanderbilt University School of Medicine, Nashville, USA, Department of Biological Sciences, Vanderbilt University, Nashville, USA, Division of Natural and Computational Sciences, Gwynedd Mercy University, Gwynedd Valley, USA, Department of Chemistry, Villanova University, Villanova, USA
Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen
Tryptophan, immunomodulation, amphibian declines, Batrachochytrium dendrobatidis, kynurenine, methylthioadenosine, splenocytes
Structure type: monomer
Location inside paper: Fig. 1, A, methylthioadenosine
Trivial name: methylthioadenosine
Compound class: glycoside, nucleoside
Methods: 1H NMR, inhibition studies, biological assays, HPLC, UV, LC-MS, cell growth, HR-ESI-MS, centrifugation
Biological activity: compound has immunomodulatory effects in mammalian systems and inhibits proliferation of X. laevis splenocytes at concentrations ≥ 100 μM and inhibits division and survival of Jurkat T cells at concentrations ≥ 10 μM
Related record ID(s): 49623, 49625, 49635, 49636, 49698
NCBI Taxonomy refs (TaxIDs): 109871
Show glycosyltransferases
There is only one chemically distinct structure:
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