Michael Federle
Cell-to-cell communication in bacteria is a fascinating area of biological research, but its significance to human health lies in the potential to develop technologies that harness bacterial behavior by communication modulation. Our laboratory is committed to understanding how bacteria coordinate gene expression and behavior across microbial populations through chemical communication. This process, referred to as quorum sensing (QS), is an established mechanism by which bacteria control activities, which include defending microbial communities, coordinating assaults on competitors or host immune systems, and acquiring new genetic information by horizontal gene transfer.
We have contributed to the field of quorum sensing by identifying new intercellular communication pathways in Gram-positive bacterial pathogens and by identifying small molecules that interfere with signaling. We hypothesize that interrupting pheromone-receptor interactions will block communication pathways that coordinate events leading to pathogenesis. Our long-term goal is to develop new therapeutics that will prevent and treat bacterial infections, or that promote a robust and healthy microflora, by modulating communication networks.
Our team has identified that the Rgg2/Rgg3 QS system in Streptococcus pyogenes results in a diminished inflammatory response from host cells. This effect persists even when other pro-inflammatory agonists are present. Research suggests that carbohydrate-based alterations on the bacterial cell wall could be responsible for this effect. The precise host cell mechanisms being triggered or suppressed, leading to the immunosuppressed phenotype, are still unclear. Additionally, ongoing investigations aim to understand the implications of this suppression on in vivo infections and potential fitness benefits to the bacteria.
Our lab has also observed that under certain conditions, S. pyogenes produces an orange-pink pigment, previously undocumented in this species. Despite requiring QS-enabled media to produce this pigment, QS itself appears to inhibit its production. Current research aims to identify this pigment, its production process, and its potential function as a virulence factor.
Abstracts this author is presenting: