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Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen.
Mika-Gospodorz, Bozena Giengkam, Suparat Westermann, Alexander J Wongsantichon, Jantana Kion-Crosby, Willow Chuenklin, Suthida Wang, Loo Chien Sunyakumthorn, Piyanate Sobota, Radoslaw M Subbian, Selvakumar
Mika-Gospodorz, Bozena
Giengkam, Suparat
Westermann, Alexander J
Wongsantichon, Jantana
Kion-Crosby, Willow
Chuenklin, Suthida
Wang, Loo Chien
Sunyakumthorn, Piyanate
Sobota, Radoslaw M
Subbian, Selvakumar
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2020-07-03
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Abstract
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.
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Nat Commun. 2020;11(1):3363. Published 2020 Jul 3. doi:10.1038/s41467-020-17094-8.
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en
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2041-1723
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Attribution-NonCommercial-ShareAlike 4.0 International