Simultaneous transcriptional profiling of bacteria and their host cells by heterogeneous RNA-Seq (hRNA-Seq)

We developed heterogeneous RNA-Seq (hRNA-Seq) to simultaneously capture prokaryotic and eukaryotic expression profiles of bacteria-infected cells. As proof of principle, hRNA-Seq was applied to Chlamydia-infected cells, successfully obtaining the transcriptomes of both Chlamydia and their host cells at 1 and 24 hours post-infection. Substantial transcription was found in the immediate-early period of infection for both Chlamydia and the host cell. We discovered possible chlamydial immune dampening strategies, and putative positive feedback mechanisms for Chlamydia-induced fibrotic scarring. In summary, hRNA-Seq helps to reveal the complex interplay between invading bacterial pathogens and their host mammalian cells and is immediately applicable to any bacteria/host cell interaction.