Development of Quorum Sensing Inhibitors for Streptococcus pneumoniae Through Optimization of the Hydrophobic Binding Face and Substitution of the N-Terminus Residue

Authors: Alec Buttner, Department of Chemistry, Moravian College Emilee Engler, Department of Chemistry, Moravian College Tahmina Milly, Department of Chemistry, University of Nevada Reno Kylie Chichura, Department of Chemistry, Moravian College Faculty Mentors: Michael Bertucci, Ph.D., Department of Chemistry, Moravian College Yftah Tal-Gan, Ph.D., Department of Chemistry, Moravian College Moravian College Address: 1200 Main St, Bethlehem, PA 18018 University of Nevada, Reno Address: 1664 N Virginia St, Reno, NV 89557

Streptococcus pneumoniae is a gram-positive bacterium that is the cause of many illnesses such as pneumonia and sepsis. One key component in the ability of S. pneumoniae to infect its host (i.e. humans) is its ability to quorum sense. Quorum sensing is a cell-density dependent form of bacterial communication in which bacteria reach a threshold density and a signaling molecule is released, allowing cell colonies to initiate group activity such as infectivity and pathogenicity. One of the key signaling molecules in the S. pneumoniae quorum-sensing circuit is the Competence Stimulating Peptide 1 (CSP1) which binds to the corresponding ComD1 receptor. One aspect of this research works to make modifications in the hydrophobic binding face of CSP1 to improve its binding to the ComD1 receptor, while another includes a substitution of Alanine for Glutamic Acid in the first position which changes the peptide from an activator to an inhibitor. This research has resulted in improved binding in positions 4, 7, 12, and 13 of the hydrophobic binding face of CSP1. These peptides with improved binding were effectively turned from activators into inhibitors for the S. pneumoniae quorum-sensing circuit. This has led to the discovery of the most potent ComD1 activating and inhibiting peptides to date. By developing effective inhibitors for quorum-sensing in S. pneumoniae, the ability of the bacteria to infect humans and become pathogenic can be minimized.

Additional Abstract Information

Presenters: Alec Buttner, Emilee Engler

Institution: Moravian College

Type: Poster

Subject: Biochemistry

Status: Approved

Time and Location

Session: Poster 1
Date/Time: Mon 1:30pm-2:30pm
Session Number: 2115