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Elucidating Peptide Pheromone Signaling in Pathogen Conversations to Understand Advantages of Social Cooperation
Author(s) -
Federle Michael J
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb198
Subject(s) - quorum sensing , biology , signal transduction , virulence , streptococcus pyogenes , cell signaling , sex pheromone , pheromone , effector , receptor , genetics , microbiology and biotechnology , gene , computational biology , bacteria , staphylococcus aureus
Cell‐to‐cell communication (quorum sensing) of Gram‐positive bacteria commonly employs peptide pheromones that transmit information between bacterial cells to facilitate coordinated gene expression across a population. In bacterial pathogens, quorum‐sensing pathways are found to contribute to virulence, biofilm development, antibiotic resistance and species evolution. In Firmicutes , pheromone receptors that are located within the cytosol encompasses a large protein family, designated RNPP (Rap/Npr/PlcR/PrgX), that contains a common structural domain responsible for binding pheromones. Though related by structure, primary amino acid sequences of RNPP proteins and their corresponding peptide ligands are disparate. Likewise, the interactions between receptors and ligands, and the mechanisms of activation resulting from these interactions are empirically unique individually for the few prototypical systems studied and thus, overall, the family remains underexplored. It is our goal to elucidate the sensory‐transduction mechanisms of these molecular switches to facilitate methodologies that can be used to modulate communication pathways to treat or prevent disease. Using genetic, biochemical, structural and chemical‐biology approaches, we have begun to elucidate signaling pathways among streptococcal species, have characterized receptors and their interactions with ligands, and have identified modulatory compounds that interfere with normal signaling. For the Rgg2/3 signaling pathway in Streptococcus pyogenes , pheromones induce phenotypes that are consistent with an ability for bacteria to colonize the host asymptomatically, and we hypothesize that social coordination of this behavior reinforces conformity to avoid host innate‐immunity stimulation. Support or Funding Information NIH R01AI091779 and R01AI425452, and the Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases