Elucidation of host-pathogen interactions during Orientia tsutsugamushi infection and translation into new diagnostics

Orientia tsutsugamushi (Ot) is an obligate intracellular Rickettsiales bacterium that causes the mite-borne human disease scrub typhus, a leading cause of severe febrile illness in Asia and an emerging public health challenge in other parts of the world. Scrub typhus is the most significant rickettsial disease in severity and prevalence.

Its fundamental biology is not well understood, limiting advances in the development of urgently needed vaccines, diagnostics, and treatments.

My lab has spent the past eight years working in the USA and Thailand to develop Ot into a robust and experimentally tractable system. We are now poised to gain a deep understanding of the cellular microbiology of this organism. We recently identified Ot subpopulations with distinct physical properties.

This project will characterize the mechanism whereby these Ot forms enter cells and escape detection by the endolysosomal pathway.

We will also investigate how Ot exploits the host cellular machinery to grow and develop; budding-off mechanisms preceding bacterial dissemination also will be explored. Our knowledge of Ot heterogeneity will provide essential insights for development of improved diagnostic tools.

Our physical presence in Thailand and our local partners who can rapidly apply laboratory findings to the clinic will benefit at-risk populations the most.