Publication: Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
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Issued Date
2020-12-01
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20411723
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2-s2.0-85087419564
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.11, No.1 (2020)
Suggested Citation
Bozena Mika-Gospodorz, Suparat Giengkam, Alexander J. Westermann, Jantana Wongsantichon, Willow Kion-Crosby, Suthida Chuenklin, Loo Chien Wang, Piyanate Sunyakumthorn, Radoslaw M. Sobota, Selvakumar Subbian, Jörg Vogel, Lars Barquist, Jeanne Salje Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen. Nature Communications. Vol.11, No.1 (2020). doi:10.1038/s41467-020-17094-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/57667
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Title
Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
Other Contributor(s)
Helmholtz-Institut für RNA-basierte Infektionsforschung
A-Star, Institute of Molecular and Cell Biology
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Julius-Maximilians-Universität Würzburg
Nuffield Department of Medicine
Rutgers University
State University of New Jersey
A-Star, Institute of Molecular and Cell Biology
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Julius-Maximilians-Universität Würzburg
Nuffield Department of Medicine
Rutgers University
State University of New Jersey
Abstract
© 2020, The Author(s). 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.