Streptococcus is a genus of gram-positive bacterium which utilizes quorum sensing for cell-cell communication. Quorum sensing allows for cells of the same species to communicate through specific peptides and coordinate cellular processes amongst themselves. There are two species at the focus of our research: Streptococcus pneumoniae and Streptococcus gordonii. S. pneumoniae, an opportunistic human pathogen, relies on the competence-stimulating peptide (CSP) to gather extracellular DNA and develop resistance mechanisms. S. gordonii, a lesser known species, is an oral bacterium that utilizes a similar CSP pathway of communication. For both of these species, the goal is to modify the peptide necessary to their quorum sequencing to both inhibit and outcompete the natural peptide. Through solid phase peptide synthesis (SPPS), CSP-1 variations have been created with differing substitutions, using D-amino acids as well as unnatural amino acids the body cannot produce. The peptides were purified and tested as an inhibitor/activator using bioassays. For S. pneumoniae, a polysubstituted CSP-1 peptide was tested for its effectiveness as an inhibitor based on previous results of successful single and double substitutions. The creation of peptides with D-amino acid substitutions is currently in progress to test the impact this has on effectiveness of the peptide, which will be used later to determine potential substitutions that can be made dependent on the hydrophobic interactions.

Development of CSP derivatives utilizing amino acid substitutions to measure changes in activation and inhibition

ACS Spring 2022

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