Dysregulation of antimicrobial peptide gene expression

该研究解决了体表上皮细胞的抗菌反应，特别是这些防御的失败如何导致机会性细菌感染的发展。 细菌性肺炎是造成肉牛生产经济损失的重要原因，也是研究宿主、病原体和环境之间复杂相互作用的范例。 拟议的研究调查了抗菌肽对一系列牛呼吸道病原体的活性，以及增加这些天然抗菌产品产量的刺激因素。 我们以前观察到，皮质类固醇和病毒感染损害这些抗菌肽的合成，这种影响可能介导的压力相关的细菌感染的易感性。 这种效应将在体内得到证实，并将阐明细胞内信号转导途径。 将测试人工刺激这些反应作为预防细菌性肺炎的新方法的潜力。 最后，在壶菌病的背景下，同样的反应进行了调查，这是一种新出现的青蛙真菌疾病，是全球两栖动物物种减少和灭绝的原因之一。有人提出，压力相关的抗菌肽合成失败是全球气候变化，局部环境条件的改变，增加易感性，这种皮肤感染性疾病之间的联系。 这些研究将阐明抗菌肽基因表达的失败是否以及如何导致两种似乎有许多相似之处的重要疾病-肉牛的细菌性肺炎和青蛙的壶菌病。 这些发现有望改善控制肉牛中这种常见疾病的策略，以及更好地了解环境影响是否以及如何影响青蛙种群对这种新兴传染病的易感性。

The research addresses antibacterial responses of epithelial cells at body surfaces, and particularly how failure of these defences leads to development of opportunistic bacterial infections. Bacterial pneumonia is an important cause of economic loss in beef production, and a paradigm for studying the complex interactions among host, pathogens, and the environment. The proposed research investigates the activity of antimicrobial peptides against a range of bovine respiratory pathogens, and the stimuli that increase production of these natural antibacterial products. We previously observed that corticosteroids and viral infection impair the synthesis of these antimicrobial peptides, and this effect may mediate stress-related susceptibility to bacterial infection. This effect will be confirmed in vivo, and the intracellular signalling pathways responsible will be elucidated. The potential for artificial stimulation of these responses as a novel method to prevent bacterial pneumonia will be tested. Finally, the same response is investigated in the context of chytridiomycosis, an emerging fungal disease of frogs that is one reason for global declines and extinction of amphibian species. It is proposed that stress-related failure of antimicrobial peptide synthesis is a link between global climate change, local alteration of environmental conditions, and increased predisposition to this cutaneous infectious disease. These studies will elucidate whether and how a failure of antimicrobial peptide gene expression leads to two important diseases that appear to share many similarities--bacterial pneumonia in beef cattle, and chytridiomycosis in frogs. These findings are expected to lead to improved strategies to control this common disease in beef cattle, as well as an improved understanding of whether and how environmental influences affect susceptibility of frog populations to this emerging infectious disease.