TY - JOUR T1 - Dual RNA-seq provides insight into the biology of the neglected intracellular human pathogen <em>Orientia tsutsugamushi</em> JF - bioRxiv DO - 10.1101/743641 SP - 743641 AU - Bozena Mika-Gospodorz AU - Suparat Giengkam AU - Alexander J. Westermann AU - Jantana Wongsantichon AU - Willow Kion-Crosby AU - Suthida Chuenklin AU - Loo Chien Wang AU - Piyanate Sunyakumthorn AU - Radoslaw M. Sobota AU - Selvakumar Subbian AU - Jörg Vogel AU - Lars Barquist AU - Jeanne Salje Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/29/743641.abstract N2 - Emerging and neglected diseases pose challenges as their biology is frequently poorly understood, and genetic tools often do not exist to manipulate the responsible pathogen. Organism agnostic sequencing technologies offer a promising approach to understand the molecular processes underlying these diseases. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium and the causative agent of 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, we investigated the transcriptional architecture of Ot, including operon structure and non-coding RNAs, and found evidence for wide-spread post-transcriptional antisense regulation. We compared the host response to two clinical isolates and identified distinct immune response networks that are up-regulated in response to each strain, leading to predictions of relative virulence which were confirmed 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. ER -