Meeting Abstract
Amphibians are declining in many parts of the world due to an emerging fungal disease, chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd). Previously, we showed that Bd cells and supernatant (Sup) factors inhibited lymphocytes by induction of apoptosis. Some of the toxic factors are associated with the cell wall. Cell walls alone inhibited lymphocytes, and interference with cell-wall synthesis inhibited the production of lymphotoxic factors. Other inhibitory factors are small metabolites. Using HPLC with UV-Visible detection, Bd and non-pathogenic Homolaphlyctis polyrhiza (Hp) supernatants were analyzed. Bd Sup consisted of two major components not present in the Hp Sup. One major metabolite was identified as methylthioadenosine (MTA). MTA inhibited X. laevis splenocytes at concentrations of less than or equal to 100 µM and inhibited survival of Jurkat T cells at concentrations of less than or equal to 10 µM. Another major component was tryptophan, which was not inhibitory. However, an oxidized tryptophan metabolite, kynurenine, was detected in the Bd Sup and suppressed proliferation of frog lymphocytes and Jurkat cells at supraphysiological concentrations. Although kynurenine alone was only inhibitory at mM concentrations, the addition of 10 µM MTA significantly enhanced the activity of kynurenine at much lower concentrations suggesting a synergistic inhibition of T cell proliferation. Support: National Science Foundation IOS-1121758 and DEB-1136662.
