Collaborative Research: Host and Pathogen Interactions in the Amphibian Disease, Chytridiomycosis

合作研究：两栖动物疾病壶菌病中宿主和病原体的相互作用

• 批准号: 1557592
• 负责人: Kevin Minbiole
• 金额: $ 15.98万
• 依托单位: Villanova University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557592&HistoricalAwards=false
• 关键词: Collaborative; Research; Host; Pathogen; Interactions

Amphibians (frogs, toads, salamanders) are central members of many biological communities. As tadpoles, they consume vegetation in streams and ponds, and as adults, they consume large numbers of insect prey. They, in turn, are eaten by snakes, birds and small mammals. Thus, the balance of many ecosystems depends on amphibians. Currently, nearly one third of amphibian species worldwide are at risk for development of a fungal skin disease that has driven more than 150 species into extinction. Fungi that cause disease have complex interactions with their hosts, and host immune defenses generally keep them in check. However, many pathogenic fungi have developed immune evasion strategies. This project will investigate the mechanisms used by a pathogenic fungus to impair the immune system. It will examine the chemical nature of factors released by the fungus that inhibit lymphocytes. If the factors are novel, they may be developed as therapeutic agents to control immune disorders. Success in this investigation will greatly advance our understanding of the specific mechanisms that are used by this fungus to evade immune clearance and may suggest novel virulence mechanisms used by other pathogenic fungi that affect humans.Batrachochytrium dendrobatidis (Bd) is a skin fungus that is one cause of worldwide declines and extinctions of amphibians. Fungi that infect vertebrates have complex interactions with their hosts, and host immune defenses generally keep them in check. However, many pathogenic fungi have developed immune evasion strategies. This project will investigate the mechanisms by which Bd inhibits lymphocyte functions. Investigators and students at Vanderbilt University School of Medicine, Villanova University, and Gwynedd Mercy University will investigate the immunotoxic molecules produced by Bd and a second amphibian fungus, Batrachochytrium salamandrivorans. The objectives are to isolate and characterize immunomodulatory and cytotoxic molecules produced by pathogenic Bd strains responsible for chytridiomycosis; (2) to further examine the mechanisms of immune system evasion by Bd, the subsets of lymphoid cells affected, and to determine whether other non-lymphoid cells are targets of Bd factors; (3) to determine whether Batrachochytrium from different geographic locations and with differing genetic makeup vary in their metabolic profiles and production of molecules toxic to lymphocytes and other cells.

两栖动物(青蛙、蟾蜍、火蜥蜴)是许多生物群落的中心成员。作为蝌蚪，它们吃溪流和池塘中的植被，作为成年，它们吃大量的昆虫猎物。反过来，它们又被蛇、鸟和小型哺乳动物吃掉。因此，许多生态系统的平衡依赖于两栖动物。目前，全球近三分之一的两栖动物物种面临着罹患真菌皮肤病的风险，这种疾病已导致150多种物种灭绝。导致疾病的真菌与宿主有复杂的相互作用，宿主的免疫防御通常会使它们受到控制。然而，许多病原真菌已经开发出免疫逃避策略。这个项目将研究一种致病真菌破坏免疫系统的机制。它将检查真菌释放的抑制淋巴细胞的因子的化学性质。如果这些因素是新的，它们可能会被开发为控制免疫疾病的治疗剂。这项研究的成功将极大地促进我们对这种真菌逃避免疫清除的具体机制的了解，并可能为其他影响人类的病原真菌提供新的毒力机制。树状巴氏杆菌(Batrachochytrium Dendrobatidis，Bd)是一种皮肤真菌，是全球两栖动物减少和灭绝的原因之一。感染脊椎动物的真菌与宿主有复杂的相互作用，宿主的免疫防御通常会抑制它们。然而，许多病原真菌已经开发出免疫逃避策略。本项目将研究BD抑制淋巴细胞功能的机制。范德比尔特大学医学院、维拉诺瓦大学和格温内德慈善大学的研究人员和学生将研究Bd和另一种两栖真菌Batrachochytrium salamandrivans产生的免疫毒性分子。其目的是分离和鉴定导致棘球菌病的Bd致病菌株产生的免疫调节和细胞毒分子；(2)进一步研究Bd、受影响的淋巴细胞亚群逃避免疫系统的机制，并确定其他非淋巴细胞是否是Bd因子的靶标；(3)确定来自不同地理位置、具有不同基因组成的巴氏杆菌是否在其代谢谱和产生对淋巴细胞及其他细胞有毒的分子方面存在差异。