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Photo of Michael Federle

Michael Federle

Associate Professor, Medicinal Chemistry and Pharmacognosy

Center Affiliate, Center for Biomolecular Sciences

Contact Information

900 S. Ashland Ave (870)
3152 MBRB
Chicago, IL 60607

Phone: (312) 413-0213

Website: https://sites.google.com/view/uicfederlelab

Lab Positions Available: https://sites.google.com/view/uicfederlelab

Research Lab Summary

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.

Intellectual Contributions

Journal Article

  • Wilkening RV, Chang JC, Federle M. "PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing". Mol Microbiol. 2016;99(1):71-87.
  • Chang JC, Jimenez JC, Federle M. "Induction of a quorum sensing pathway by environmental signals enhances group A streptococcal resistance to lysozyme". Mol Microbiol. 2015;97(6):1097-113.
  • Parashar V, Aggarwal C, Federle M, Neiditch MB. "Rgg protein structure-function and inhibition by cyclic peptide compounds". Proc Natl Acad Sci U S A. 2015;112(16):5177-82.
  • Aggarwal C, Jimenez Romaguera JC, Lee H, Chlipala GE, Ratia K, Federle M. "Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci.". mBio. 2015;6(3):e00393-15. doi:10.1128/mBio.00393-15.
  • Aggarwal C, Jimenez JC, Nanavati D, Federle M. "Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation". J Biol Chem. 2014;289(32):22427-36.
  • Cook L, Federle M. "Peptide pheromone signaling in Streptococcus and Enterococcus". FEMS Microbiol Rev. 2014;38(3):473-92.
  • Jimenez JC, Federle M. "Quorum sensing in group A Streptococcus". Front Cell Infect Microbiol. 2014;4:127.
  • Marks LR, Mashburn-Warren L, Federle M, Hakansson AP. "Streptococcus pyogenes biofilm growth in vitro and in vivo and its role in colonization, virulence, and genetic exchange". J Infect Dis. 2014;210(1):25-34.
  • Lasarre B, Aggarwal C, Federle M. "Antagonistic Rgg regulators mediate quorum sensing via competitive DNA binding in Streptococcus pyogenes". MBio. 2013;3(6).
  • LaSarre B, Federle M. "Exploiting quorum sensing to confuse bacterial pathogens". Microbiol Mol Biol Rev. 2013;77(1):73-111.
  • Cook L, Lasarre B, Federle M. "Interspecies Communication among Commensal and Pathogenic Streptococci". MBio. 2013;4(4).
  • Lasarre B, Chang JC, Federle M. "Redundant group a streptococcus signaling peptides exhibit unique activation potentials". J Bacteriol. 2013;195(18):4310-8.
  • Buhrman JS, Cook L, Rayahin JE, Federle M, Gemeinhart RA. "Proteolytically activated anti-bacterial hydrogel microspheres". Journal of Controlled Release. 2013;(171(3)):2882-2895. doi:10.1016/j.jconrel.2013.06.023.
  • Buhrman JS, Rayahin JE, Cook L, Federle M, Gemeinhart RA. "Active, soluble recombinant melittin purified by extracting insoluble lysate of Escherichia coli without denaturation". Biotechnology Progress. 2013;(29(5)):1150-1157. doi:10.1002/btpr.1784.
  • Desai K, Mashburn-Warren L, Federle M, Morrison DA. "Development of competence for genetic transformation of Streptococcus mutans in a chemically defined medium". J Bacteriol. 2012;194(15):3774-80.
  • Federle M. "Pathogenic streptococci speak, but what are they saying?". Virulence. 2012;3(1):92-4.
  • Mashburn-Warren L, Morrison DA, Federle M. "The cryptic competence pathway in Streptococcus pyogenes is controlled by a peptide pheromone". J Bacteriol. 2012;194(17):4589-600.
  • LaSarre B, Federle M. "Regulation and consequence of serine catabolism in Streptococcus pyogenes". J Bacteriol. 2011;193(8):2002-12.
  • Chang JC, LaSarre B, Jimenez JC, Aggarwal C, Federle M. "Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development". PLoS Pathog. 2011;7(8):e1002190.
  • Mashburn-Warren L, Morrison DA, Federle M. "A novel double-tryptophan peptide pheromone controls competence in Streptococcus spp. via an Rgg regulator". Mol Microbiol. 2010;78(3):589-606.
  • Federle M. "Autoinducer-2-based chemical communication in bacteria: complexities of interspecies signaling". Contrib Microbiol. 2009;16:18-32.
  • Neiditch MB, Federle M, Pompeani AJ, Kelly RC, Swem DL, Jeffrey PD, Bassler BL, Hughson FM. "Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing". Cell. 2006;126(6):1095-108.
  • Neiditch MB, Federle M, Pompeani AJ, Kelly RC, Swem DL, Jeffrey PD, Bassler BL, Hughson FM. "Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing". Cell. 2006;126(6):1095-108.
  • Semmelhack MF, Campagna SR, Federle M, Bassler BL. "An expeditious synthesis of DPD and boron binding studies". Org Lett. 2005;7(4):569-72.
  • Neiditch MB, Federle M, Miller ST, Bassler BL, Hughson FM. "Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2". Mol Cell. 2005;18(5):507-18.
  • Neiditch MB, Federle M, Miller ST, Bassler BL, Hughson FM. "Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2". Mol Cell. 2005;18(5):507-18.
  • Semmelhack MF, Campagna SR, Hwa C, Federle M, Bassler BL. "Boron binding with the quorum sensing signal AI-2 and analogues". Org Lett. 2004;6(15):2635-7.

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