Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine.

Autor:	Rollins-Smith LA; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA louise.rollins-smith@vanderbilt.edu.; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Ruzzini AC; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA., Fites JS; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA., Reinert LK; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Hall EM; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Joosse BA; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA., Ravikumar VI; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Huebner MI; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Aka A; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Kehs MH; Division of Natural and Computational Sciences, Gwynedd Mercy University, Gwynedd Valley, Pennsylvania, USA., Gillard BM; Division of Natural and Computational Sciences, Gwynedd Mercy University, Gwynedd Valley, Pennsylvania, USA., Doe E; Department of Chemistry, Villanova University, Villanova, Pennsylvania, USA., Tasca JA; Department of Chemistry, Villanova University, Villanova, Pennsylvania, USA., Umile TP; Division of Natural and Computational Sciences, Gwynedd Mercy University, Gwynedd Valley, Pennsylvania, USA.; Department of Chemistry, Villanova University, Villanova, Pennsylvania, USA., Clardy J; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA., Minbiole KPC; Department of Chemistry, Villanova University, Villanova, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2019 Apr 23; Vol. 87 (5). Date of Electronic Publication: 2019 Apr 23 (Print Publication: 2019).
DOI:	10.1128/IAI.00035-19
Abstrakt:	Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis , which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis , but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B. dendrobatidis SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 μM and is found at concentrations between 1 and 10 μM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 μM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 μM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 μM. We interpret these results to suggest that B. dendrobatidis produces an "armamentarium" of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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