Development of Peptide-Based Tools to Study Cell-Cell Communication in Bacteria

DRA lecture held by Professor Yftah Tal-Gan, University of Nevada, Reno, USA

Streptococcus cristatus belongs to the Mitis group of streptococci and is an early colonizer of the human oral cavity. This species has recently been reclassified from Streptococcus oligofermentans and as such, much information regarding the competence regulon and its regulatory role in modulating downstream phenotypes remains unknown. We set out to investigate the role of the competence-stimulating peptide (CSP) in competence regulon activation and modulation, as well as define the resultant transcriptomic and phenotypic effects of CSP exposure. To this end, following confirmation of the CSP identity, structure activity relationship (SAR) analyses were conducted and revealed residues integral for CSP::ComD binding and activation, as well as provided insights about the CSP secondary structure. The ability of synthesized CSP analogs to modulate the competence regulon was quantified with the aid of a newly developed luciferase-based reporter strain, after which the biological activity was correlated with peptide secondary structure derived through CD analysis. Furthermore, RNA-seq was utilized to gain broader insights about subsequent transcriptomic changes following CSP incubation, while phenotypic assays helped with visualizing resultant expression profiles. Lastly, to further explore the potential of S. cristatus as a potential biotherapeutic against the oral pathogen, Streptococcus mutans, interspecies competition assays were used to evaluate interactions between these two species.

The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Professor Christian A. Olsen, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.

The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.