Quantifying the transcriptome of a human pathogen: Exploring transcriptional adaptation of Streptococcus pneumoniae under infection-relevant conditions

Streptococcus pneumoniae, or the pneumococcus, is a Gram positive opportunistic pathogen and the etiologic agent of lower respiratory tract infections, sepsis and meningitis. The pneumococcal genome is relatively small (~2 Mbps), yet laden with genomic features, both coding-sequences and non-coding regulatory structures. This compact genome empowers the pneumococcus to successfully colonize the human nasopharyngeal passage and to survive host immune responses in infection sites. Recent sequencing technologies allow high-resolution and precise quantification of genome-wide transcripts abundance. By exploiting these technologies, we defined genome-wide transcriptional units as well as the exact start and termination sites. Furthermore, we have emphasized the emerging role of pneumococcal RNA in regulating the gene expression. In addition, we have shown that the pneumococcal genome is actively transcribed in response to a wide array of infection-relevant microenvironments. Next, we have established an infection model suitable for the simultaneous observation of epithelial cells and <i>S. pneumoniae</i> and have developed a rapid RNA isolation technique to preserve total RNA from both species. Dual RNA-seq highlighted a different transcriptional response in adhering pneumococci, the first step of colonization and infection. Finally, we have shared the raw data in public repositories and the analyzed data in easy-to-use online browsers (www.veeninglab.com/resources). We invite the research community to explore, exploit and build their own hypothesis from these rich datasets.