The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state
<i>Orientia tsutsugamushi</i> (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 plas...
मुख्य लेखकों: | , , , , , , , , , , , |
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स्वरूप: | Journal article |
भाषा: | English |
प्रकाशित: |
Springer Nature
2022
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विषय: |
_version_ | 1826310383449669632 |
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author | Atwal, S Wongsantichon, J Giengkam, S Saharat, K Pittayasathornthun, YJ Chuenklin, S Wang, LC Chung, T Huh, H Lee, S-H Sobota, RM Salje, J |
author_facet | Atwal, S Wongsantichon, J Giengkam, S Saharat, K Pittayasathornthun, YJ Chuenklin, S Wang, LC Chung, T Huh, H Lee, S-H Sobota, RM Salje, J |
author_sort | Atwal, S |
collection | OXFORD |
description | <i>Orientia tsutsugamushi</i> (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. |
first_indexed | 2024-03-07T07:51:37Z |
format | Journal article |
id | oxford-uuid:3d8cd0c4-80d8-438e-89e8-a90d3229913d |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T07:51:37Z |
publishDate | 2022 |
publisher | Springer Nature |
record_format | dspace |
spelling | oxford-uuid:3d8cd0c4-80d8-438e-89e8-a90d3229913d2023-07-21T13:34:46ZThe obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular stateJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d8cd0c4-80d8-438e-89e8-a90d3229913dBacterial developmentCellular microbiologyEnglishSymplectic ElementsSpringer Nature2022Atwal, SWongsantichon, JGiengkam, SSaharat, KPittayasathornthun, YJChuenklin, SWang, LCChung, THuh, HLee, S-HSobota, RMSalje, J<i>Orientia tsutsugamushi</i> (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. |
spellingShingle | Bacterial development Cellular microbiology Atwal, S Wongsantichon, J Giengkam, S Saharat, K Pittayasathornthun, YJ Chuenklin, S Wang, LC Chung, T Huh, H Lee, S-H Sobota, RM Salje, J The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title | The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title_full | The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title_fullStr | The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title_full_unstemmed | The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title_short | The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
title_sort | obligate intracellular bacterium orientia tsutsugamushi differentiates into a developmentally distinct extracellular state |
topic | Bacterial development Cellular microbiology |
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