This is a great paper! It talks about using the dual-RNA-seq of both the pathogen and the host at various time points, simultaneously in a Salmonella infection. They have used this technique to illustrate the role of some sRNA in virulence and pathogenesis. The idea itself is unique! The authors used Ilumina Sequencing, FACS, micro-array and various other techniques to reveal the molecular impact of bacterial riboregulators. It was a joyful journey to go through this paper!
Dual RNA-seq unveils noncoding RNA functions in host–pathogen interactions
Alexander J. Westermann1, Konrad U. Förstner1,2, Fabian Amman3,4, Lars Barquist1, Yanjie Chao1, Leon N. Schulte1, Lydia Müller3, Richard Reinhardt5, Peter F. Stadler3,4,6,7 & Jörg Vogel1,8
doi:10.1038/nature16547

Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic ‘dual RNA-seq’ approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK–STAT signalling, and we identify infection- specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.