title: Chemoproteomic profiling of host and pathogen enzymes active in cholera.
abstract: Activity-based protein profiling (ABPP) is a chemoproteomic tool for detecting active enzymes in complex biological systems. We used ABPP to identify secreted bacterial and host serine hydrolases that are active in animals infected with the cholera pathogen Vibrio cholerae. Four V. cholerae proteases were consistently active in infected rabbits, and one, VC0157 (renamed IvaP), was also active in human choleric stool. Inactivation of IvaP influenced the activity of other secreted V. cholerae and rabbit enzymes in vivo, and genetic disruption of all four proteases increased the abundance of intelectin, an intestinal lectin, and its binding to V. cholerae in infected rabbits. Intelectin also bound to other enteric bacterial pathogens, suggesting that it may constitute a previously unrecognized mechanism of bacterial surveillance in the intestine that is inhibited by pathogen-secreted proteases. Our work demonstrates the power of activity-based proteomics to reveal host-pathogen enzymatic dialog in an animal model of infection.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Stavroula K
authors.initials: SK
authors.lastname: Hatzios
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Department of Pharmacy, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.
authors.forename: Sören
authors.initials: S
authors.lastname: Abel
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: Martell
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Hubbard
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sasabe
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Munera
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Clark
authors.affiliation: The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bachovchin
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, USA.
authors.forename: Eranthie
authors.initials: E
authors.lastname: Weerapana
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D000818:Animals; D002771:Cholera / Q000201:enzymology / Q000382:microbiology; D004195:Disease Models, Animal; D005243:Feces / Q000201:enzymology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D007422:Intestines / Q000201:enzymology / Q000382:microbiology; D037102:Lectins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis; D040901:Proteomics / Q000379:methods*; D011817:Rabbits; D012697:Serine Endopeptidases / Q000378:metabolism; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D037102:Lectins; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases