Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen

Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamush...

Full description

Bibliographic Details
Main Authors: Mika-Gospodorz, B, Giengkam, S, Westermann, AJ, Wongsantichon, J, Kion-Crosby, W, Chuenklin, S, Wang, LC, Sunyakumthorn, P, Sobota, RM, Subbian, S, Vogel, J, Barquist, L, Salje, J
Format: Journal article
Language:English
Published: Springer Nature 2020
_version_ 1826290499335487488
author Mika-Gospodorz, B
Giengkam, S
Westermann, AJ
Wongsantichon, J
Kion-Crosby, W
Chuenklin, S
Wang, LC
Sunyakumthorn, P
Sobota, RM
Subbian, S
Vogel, J
Barquist, L
Salje, J
author_facet Mika-Gospodorz, B
Giengkam, S
Westermann, AJ
Wongsantichon, J
Kion-Crosby, W
Chuenklin, S
Wang, LC
Sunyakumthorn, P
Sobota, RM
Subbian, S
Vogel, J
Barquist, L
Salje, J
author_sort Mika-Gospodorz, B
collection OXFORD
description Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium that causes the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning to study the transcriptional architecture of Ot, we find evidence for wide-spread post-transcriptional antisense regulation. Comparing the host response to two clinical isolates, we identify distinct immune response networks for each strain, leading to predictions of relative virulence that are validated in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
first_indexed 2024-03-07T02:45:07Z
format Journal article
id oxford-uuid:abca48e9-1a18-492f-8638-f9af73eb2ffc
institution University of Oxford
language English
last_indexed 2024-03-07T02:45:07Z
publishDate 2020
publisher Springer Nature
record_format dspace
spelling oxford-uuid:abca48e9-1a18-492f-8638-f9af73eb2ffc2022-03-27T03:24:20ZDual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogenJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:abca48e9-1a18-492f-8638-f9af73eb2ffcEnglishSymplectic ElementsSpringer Nature2020Mika-Gospodorz, BGiengkam, SWestermann, AJWongsantichon, JKion-Crosby, WChuenklin, SWang, LCSunyakumthorn, PSobota, RMSubbian, SVogel, JBarquist, LSalje, JStudying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium that causes the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning to study the transcriptional architecture of Ot, we find evidence for wide-spread post-transcriptional antisense regulation. Comparing the host response to two clinical isolates, we identify distinct immune response networks for each strain, leading to predictions of relative virulence that are validated in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
spellingShingle Mika-Gospodorz, B
Giengkam, S
Westermann, AJ
Wongsantichon, J
Kion-Crosby, W
Chuenklin, S
Wang, LC
Sunyakumthorn, P
Sobota, RM
Subbian, S
Vogel, J
Barquist, L
Salje, J
Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title_full Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title_fullStr Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title_full_unstemmed Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title_short Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
title_sort dual rna seq of orientia tsutsugamushi informs on host pathogen interactions for this neglected intracellular human pathogen
work_keys_str_mv AT mikagospodorzb dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT giengkams dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT westermannaj dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT wongsantichonj dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT kioncrosbyw dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT chuenklins dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT wanglc dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT sunyakumthornp dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT sobotarm dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT subbians dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT vogelj dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT barquistl dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen
AT saljej dualrnaseqoforientiatsutsugamushiinformsonhostpathogeninteractionsforthisneglectedintracellularhumanpathogen