Characterization of two endopeptidases encoded by Streptococcus sanguinis

Streptococcus sanguinis, typically an oral commensal, can lead to serious human diseases like infective endocarditis if the organism gains access to the bloodstream. In this project, we are focusing on SepM, a cell surface endopeptidase found in S. sanguinis. Our earlier work with Streptococcus mutans revealed that SepM is crucial for antimicrobial peptide (AMP) secretion and dental cries formation. In group-A-streptococci, the absence of SepM homolog most likely leads to vesicle mediated M-protein secretion, a protein known to evade immune cells during infection. In S. sanguinis genome, we discovered the presence of two SepM homologs (instead of one), which is quite unusual for any streptococci. Interestingly, the function of these two SepM homologs in S. sanguinis are not well understood. Deleting either of the SepM homologs led to auto-aggregation. Analysis of the secreted proteome using mass spectrometry revealed a distinctive differential presence of proteins involved in host invasion. Our proposal aims to further investigate the functions of SepM proteins in the pathophysiology of S. sanguinis. We will identify virulence factors affected by SepM homologs and assess their impact including using a wax moth larva insect model, acknowledging the significance of S. sanguinis in diverse human diseases. Project Number: 1R21DE034331-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: SASWATI BISWAS | Institution: UNIVERSITY OF KANSAS MEDICAL CENTER, KANSAS CITY, KS | Award Amount: $426,250 | Activity Code: R21 | Study Section: Oral, Dental and Craniofacial Sciences Study Section[ODCS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11224643