Nucleic Acids and Pneumococcal Extracellular Vesicles: the Who, How and Why?

Project Summary There is a critical need to develop therapies targeting Streptococcus pneumoniae (Spn): a major human pathogen contributing to global morbidity and mortality. Bacterial communication is a critical contributor to virulence, and we propose that bacterial extracellular vesicles (EVs) contribute to communication across bacteria as well as between bacteria and the mammalian host, and in doing so, contribute to pathogenesis and serve as therapeutic targets. This proposal is based on preliminary results that demonstrate not only that viable Spn produce EVs (pEVs), but also that these pEVs are associated with DNA and RNA. Our hypothesis is that the nucleic acids on pEVs are delivered to other bacteria, and that uptake of pEV RNA by bacterial cells promotes changes in gene expression and subsequent changes in phenotypes. Conclusion of this proposal will reveal the molecules tethering nucleic acids to pEVs, uncover the sequence and localization of pEV-bound RNA, and test whether and how internalization of EVs, and RNA on pEVs, modifies the transcriptional profile of the recipient bacterial cells. This work will set the stage for future studies focused on the role of pEV-nucleic acids in driving infection-associated phenotypes and host immunity.