title: Activity of caffeic acid phenethyl ester in Caenorhabditis elegans.
abstract: OBJECTIVE
  Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans.
  
  
  RESULTS
  CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability. The CED-10(Rac-1)/PAK1 pathway was essential for immunomodulation by CAPE and was a critical component involved in the immune response to fungal pathogens.
  
  
  CONCLUSIONS
  Caenorhabditis elegans is an efficient heterologous host to evaluate immunomodulatory compounds and identify components of the pathway(s) involved in the mode of action of compounds.
authors.affiliation: Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.|MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.|Department of Entomology & Plant Pathology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Coleman
authors.affiliation: Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Komura
authors.affiliation: MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Munro
authors.affiliation: MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Wu
authors.affiliation: Chemical Biology Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
authors.forename: Rakhee R
authors.initials: RR
authors.lastname: Busanelli
authors.affiliation: Chemical Biology Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.|Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Koehler
authors.affiliation: Chemical Biology Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
authors.forename: Méryl
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Chemical Biology Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
authors.forename: Florence F
authors.initials: FF
authors.lastname: Wagner
authors.affiliation: Chemical Biology Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.|Atlas Venture, Cambridge MA 02139, USA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Holson
authors.affiliation: Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.|MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
keywords: Candida; caffeic acid phenethyl ester; innate immune response; p21 kinase; propolis