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.