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The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state

Sharanjeet Atwal, Jantana Wongsantichon, Suparat Giengkam, Kittirat Saharat, Yanin Jaiyen Pittayasathornthun, Suthida Chuenklin, Loo Chien Wang, Taerin Chung, Hyun Huh, Sang-Hyuk Lee, Radoslaw M. Sobota and Jeanne Salje ()
Additional contact information
Sharanjeet Atwal: Rutgers the State University of New Jersey
Jantana Wongsantichon: Mahidol University
Suparat Giengkam: Mahidol University
Kittirat Saharat: Rutgers the State University of New Jersey
Yanin Jaiyen Pittayasathornthun: Mahidol University
Suthida Chuenklin: Rutgers the State University of New Jersey
Loo Chien Wang: Technology and Research (A*STAR)
Taerin Chung: Rutgers University
Hyun Huh: Rutgers University
Sang-Hyuk Lee: Rutgers University
Radoslaw M. Sobota: Technology and Research (A*STAR)
Jeanne Salje: Rutgers the State University of New Jersey

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Orientia tsutsugamushi (Ot) is an obligate intracellular bacterium in the family Rickettsiaceae that causes scrub typhus, a severe mite-borne human disease. Its mechanism of cell exit is unusual amongst Rickettsiaceae, as Ot buds off the surface of infected cells enveloped in plasma membrane. Here, we show that Ot bacteria that have budded out of host cells are in a distinct developmental stage compared with intracellular bacteria. We refer to these two stages as intracellular and extracellular bacteria (IB and EB, respectively). These two forms differ in physical properties: IB is both round and elongated, and EB is round. Additionally, IB has higher levels of peptidoglycan and is physically robust compared with EB. The two bacterial forms differentially express proteins involved in bacterial physiology and host-pathogen interactions, specifically those involved in bacterial dormancy and stress response, and outer membrane autotransporter proteins ScaA and ScaC. Whilst both populations are infectious, entry of IB Ot is sensitive to inhibitors of both clathrin-mediated endocytosis and macropinocytosis, whereas entry of EB Ot is only sensitive to a macropinocytosis inhibitor. Our identification and detailed characterization of two developmental forms of Ot significantly advances our understanding of the intracellular lifecycle of an important human pathogen.

Date: 2022
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DOI: 10.1038/s41467-022-31176-9

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