Exploiting the arthropod vector: novel mechanisms of Mycobacterium leprae transmission

项目摘要 汉森氏病（HD），通常被称为麻风病，被认为是一种古老的疾病， 疾病已被根除，但在2019年，全球向世卫组织报告的新病例数 超过20万。来自世界各地的新麻风病例中， 无法与曾经接触过的另一个麻风病人联系起来。缺乏一个 合理的生物接触源可能会引起新诊断患者的严重焦虑， 助长了麻风病作为一种神秘诅咒或惩罚的污名化。在美国， 犰狳是麻风分枝杆菌的天然宿主， 54%的土著病例也是由犰狳中传播的麻风病造成的;因此，麻风病是 在美国被认为是人畜共患病认识到M.麻风病是不稳定的 环境，因此中间宿主，如节肢动物载体，可能有助于 麻风病的传播。该项目的总体目标是确定血液的病媒潜力- 喂养蜱虫以获得并传播传染性M.麻风病对脊椎动物宿主的影响另夕h M.的转录活性。将节肢动物宿主背景中的麻风与M. 麻风病转录组，而在脊椎动物宿主。结合起来，该项目将有可能确定一个 麻风的另一传播途径和M.麻风病相关分子 这个传输周期。从拟议研究中获得的数据将大大提高我们的 了解麻风病的流行病学，因为这将是第一次评估麻风病的生物学， M.麻风病感染和钝眼蜱传播。根据实地调查和实验 我们怀疑Amblyomma蜱是M.麻风病人蜱媒 能力M。麻风病尚未在受控的实验室条件下得到彻底的研究 因此，该项目发现的相关性将提供新的信息， 与麻风病的生态学和流行病学有关。

PROJECT SUMMARY Hanson’s disease (HD), more commonly known as leprosy, is thought of as an ancient disease that has been eradicated, yet in 2019, the number of new cases reported globally to the WHO was more than 200,000. Up to 80% of the new leprosy cases presenting from around the world are unable to relate ever having come in contact with another person who had leprosy. The lack of a plausible biological contact source can provoke profound anxiety in newly diagnosed patients and contributes to the stigmatization of leprosy as a mystical curse or punishment. In the United States, armadillos are a large natural reservoir of Mycobacterium leprae and the same strain of bacteria that circulates among armadillos also is responsible for 54% of the indigenous cases; thus, leprosy is recognized as a zoonosis in the United States. It is realized that M. leprae is not stable in the environment, so an intermediary host, such as an arthropod vector, may contribute to the transmission of leprosy. The overall goal of this project is to determine the vector potential for blood- feeding ticks to acquire and transmit infectious M. leprae to vertebrate hosts. Additionally, the transcriptional activity of M. leprae in an arthropod host background will be compared to the M. leprae transcriptome while in a vertebrate host. Combined, this project will potentially identify an alternate route of leprosy transmission and the M. leprae molecules putatively associated with this transmission cycle. The data generated from the proposed studies will greatly enhance our understanding of the epidemiology of leprosy as it will be the first assessment of the biology of M. leprae infection and transmission by Amblyomma ticks. Based on field surveys and experimental evidence we suspect that Amblyomma ticks are competent vectors for M. leprae. Tick vector competence for M. leprae has not been thoroughly explored under controlled laboratory conditions previously, so the relevance of the findings from this project will provide novel information that can be related to the ecology and epidemiology of leprosy.