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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
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 Jdoi
10.1038/s41467-020-17094-8subject
Has Abstractpub_date
2020-07-03 00:00:00pages
3363issue
1issn
2041-1723pii
10.1038/s41467-020-17094-8journal_volume
11pub_type
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