Chemoproteomic profiling of host and pathogen enzymes active in cholera

Stavroula K. Hatzios, Sören Abel, Julianne Martell, Troy Hubbard, Jumpei Sasabe, Diana Munera, Lars Clark, Daniel A. Bachovchin, Firdausi Qadri, Edward T. Ryan, Brigid M. Davis, Eranthie Weerapana, Matthew K. Waldor

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalNature Chemical Biology
Volume12
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Chemoproteomic profiling of host and pathogen enzymes active in cholera'. Together they form a unique fingerprint.

  • Cite this

    Hatzios, S. K., Abel, S., Martell, J., Hubbard, T., Sasabe, J., Munera, D., Clark, L., Bachovchin, D. A., Qadri, F., Ryan, E. T., Davis, B. M., Weerapana, E., & Waldor, M. K. (2016). Chemoproteomic profiling of host and pathogen enzymes active in cholera. Nature Chemical Biology, 12(4), 268-274. https://doi.org/10.1038/nchembio.2025