[Seminar] Microbial Wikileaks: Deciphering Microbial Conversations and an Opportunity to Interfere
Michael J. Federle, University of Illinois, Chicago, USA
| When |
02 Jun, 2015
from
11:00 am to 12:00 pm |
|---|---|
| Where | Auditorium |
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Seminar
Title: Microbial Wikileaks: Deciphering Microbial Conversations and an Opportunity to Interfere
Speaker: Michael J. Federle
Affiliation: University of Illinois at Chicago, Dept. of Medicinal Chemistry and Pharmacognosy, USA
Host: Karina Xavier, Bacterial Signalling Lab
Abstract:
Bacteria commonly use chemical-based cell-to-cell communication, commonly referred to as quorum sensing (QS), to coordinate a variety of behaviors across a population, including production of virulence determinants, biofilm development, and horizontal gene transfer. In recent years, the urgent need to identify new alternatives to antibiotics that fight bacterial infections has inspired the concept of inhibiting fundamental mechanisms of pathogenesis rather than inhibiting processes essential to bacterial growth. We have helped to identify in Gram-positive bacteria new intercellular communication pathways utilizing short peptide pheromones and their cognate receptors of the Rgg protein family type. In the human-restricted pathogen Streptococcus pyogenes four Rgg paralogs provide a means to regulate genes involved in pathogenesis, natural transformation, biofilm development and lysozyme resistance. It is our objective to understand the mechanisms sustaining intercellular communication in this organism and how chemical signaling contributes to pathogenesis and carriage. Secondly, because Rgg-family orthologs are widespread among pathogenic and commensal species of Firmicutes, it is our priority to develop small molecules and peptides that manipulate pheromone-dependent signaling. We have identified a fungal cyclic peptide that specifically competes with one class of Rgg–pheromone interaction, and find that it inhibits S. pyogenes biofilm development and lysozyme resistance. Going forward, it is our objective to characterize additional Rgg pathways in various species, as well as identify small-molecule modulators of these pathways in hopes of harnessing bacterial behaviors.
