MCDB seminar will be from Charles Agbavor from the Cahoon lab will be presenting their research titled:
Title: How harmless bacteria can transition into pathogens: Bacterial surface chaperones regulate Streptococcus pneumoniae cell-to-cell communication
Friday, January 17, 2025
A219B Langley Hall
12:00 PM
The human body contains trillions of harmless bacterial species. However, under certain conditions some of these microbes can transition into pathogens; the mechanisms involved in these transitions are not clear. To elucidate this mechanism, our lab uses Streptococcus pneumoniae, an opportunistic bacterial pathogen. S. pneumoniae is commonly found in the throat cavity of 5-90 % of healthy people, however, it can transition into fatal infections such as pneumonia, blood poisoning and meningitis. Recent studies suggest that certain signaling factors and importer proteins are required for the bacteria to perceive the local composition of the throat cavity including essential nutrients and competitors. This process is critical for bacterial cells to employ the release of bacterial proteins that are important for disease causation and progression. Using computational analyses and a proteomic approach, we have identified two bacterial surface chaperones (PrsA and SlrA) that regulate the activity and release of a signaling factor, phrA and 3 importer proteins, amiA/aliA/B that are known sensors of the physicochemical conditions in the host. We found that the secretion and activity of these factors are dependent on the surface chaperones that are critical for invasive disease. Using a biophysical assay, we show that the three importer proteins are bound to both PrsA and SlrA with nanomolar affinities suggesting that the importer proteins are folded by these surface chaperones. Additionally, with a promoter-bioluminescence assay, we show that the import of the signaling molecule is dependent on both chaperones and that this import is time dependent in the presence of host cells. Furthermore, we found that the importer proteins interact with the signaling molecule under host-mimicking conditions. Finally, we elucidated the molecular basis of how the chaperones interact with the signaling factor and importer proteins by solving to high resolution, the protein structures of PrsA and SlrA surface chaperones. Together, these findings may provide a new way to control S. pneumoniae infections and expand our understanding of the biology of this important human pathogen.