Active Infection & Immunity Digestion, Kidneys & Other Organs

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

Funder Wellcome Charity-funded
Recipient organisation Rutgers State University of New Jersey
Funding £2.5M
Period Aug 2022 — Jul 2027

In plain English

AI plain-English summary

Scrub typhus bacteria come in different physical forms, and researchers have just discovered that these forms enter human cells using distinct mechanisms. This matters because scrub typhus—caused by the bacterium *Orientia tsutsugamushi*—is a leading cause of severe fever in Asia and an emerging threat elsewhere, yet its fundamental biology remains poorly understood. No effective vaccine exists, and current diagnostics are inadequate. The bacterium’s ability to hide inside cells and evade the immune system has stymied progress for decades. The research team, based in the USA and Thailand, will dissect exactly how the bacterial forms slip past the cell’s endolysosomal defences, how they hijack host machinery to replicate, and how they bud off to spread. Because the team works directly in Thailand, where the disease is endemic, laboratory findings can move quickly into clinical testing. If successful, this work could lead to diagnostic tools that detect scrub typhus earlier and more accurately, reducing the number of patients who are misdiagnosed or treated too late. It also lays the groundwork for future vaccine design—though that remains a longer-term goal.

View original technical description
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.

View the original record at the funder ↗

Researchers

Jeanne Salje (EPMC Awardee)

Related Research

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Original classification

Senior Research Fellowship

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