Rollins-Smith Louise A, Fites J Scott, Reinert Laura K, Shiakolas Andrea R, Umile Thomas P, Minbiole Kevin P C
Department of Pathology, Microbiology, and Immunology, and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
Infect Immun. 2015 Dec;83(12):4565-70. doi: 10.1128/IAI.00877-15. Epub 2015 Sep 14.
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.
蛙壶菌是壶菌门中的一种真菌病原体，可引发皮肤疾病壶菌病。壶菌病被认为是一种与全球两栖动物数量减少和灭绝相关的新发传染病。尽管两栖动物拥有发达的免疫防御系统，但从皮肤清除这种病原体的能力常常受损。此前，我们表明适应性免疫系统参与了对该病原体的控制，但蛙壶菌会释放抑制体外和体内淋巴细胞反应并诱导淋巴细胞凋亡的因子。对于这种真菌释放的抑制因子的性质知之甚少。在此，我们描述了由蛙壶菌产生但与其亲缘关系密切的非致病性壶菌多根同丝壶菌不产生的三种真菌代谢产物的分离和特性。这些代谢产物是甲硫腺苷（MTA）、色氨酸以及色氨酸的氧化产物犬尿氨酸（Kyn）。单独来看，MTA和Kyn均会抑制两栖动物淋巴细胞以及Jurkat人T细胞白血病细胞系的存活和增殖。然而，共同作用时，它们在低得多的浓度下就会发挥作用。我们推测蛙壶菌能够调整其代谢以释放改变皮肤局部环境从而抑制免疫并提高病原体存活率的产物。
