Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine [Fungal and Parasitic Infections]

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 th...

Source: Infection and Immunity - April 22, 2019 Category: Infectious Diseases Authors: Rollins-Smith, L. A., Ruzzini, A. C., Fites, J. S., Reinert, L. K., Hall, E. M., Joosse, B. A., Ravikumar, V. I., Huebner, M. I., Aka, A., Kehs, M. H., Gillard, B. M., Doe, E., Tasca, J. A., Umile, T. P., Clardy, J., Minbiole, K. P. C. Tags: Fungal and Parasitic Infections Source Type: research