Our work centers on investigating chemical interventions and tools to study biological processes that impact human health. Currently, our research focuses on the synthesis of small molecules and peptides to study and modulate a mechanism of density-dependent communication in bacteria known as quorum sensing (QS). As it has been demonstrated to control virulence, competence and biofilm formation in a variety of different bacterial species, manipulating QS is recognized as a strategy for treating disease states that result from these phenotypes.
Quorum Sensing in Streptococcus pneumoniae
The ability of the opportunistic pathogen S. pneumoniae to infect a host and develop resistant mechanisms to antibiotics is controlled by QS. The signals that mediate this communication are short, helical peptides known as CSP-1 and CSP-2. In collaboration with the Tal-Gan Group at the University of Nevada, Reno, we are investigating the binding domain of CSP-1 to better understand the relationship between the peptide’s structure and its QS activity. In doing so, potent inhibitors of S. pneumoniae QS will be developed.
Quorum Sensing in Lactobacillus plantarum
QS in commensal bacteria L. plantarum has been demonstrated to control cell adherence and bacteriocin production. By understanding the fundamental structure-activity relationships between LamD, the cyclic peptide that regulates L. plantarum QS, and its cognate receptor, LamD derivatives will be synthesized capable of modulating these phenotypes. As L. plantarum and other Lactobacillus species compose a significant percentage of the human gut microbiome, enhancing these phenotype may provide a colonization advantage for these species in the presence of microbial pathogens or diseases of ecological imbalance.
Quorum Sensing in Bacillus cereus
The peptide PapR7 regulates hemolytic activity in Bacillus cereus. QS is responsible for the production of virulence factors, such as enterotoxins and hemolysins, in the opportunistic and food-borne pathogen B. cereus. In collaboration with the Hayouka Lab at the Hebrew University of Jerusalem (The Faculty of Agriculture, Food & Environment), we are investigating second generation structural modifications to the QS signaling peptide PapR to develop a chemical strategy for inhibiting these factors.