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

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)268-274
ページ数7
ジャーナルNature Chemical Biology
12
4
DOI
出版ステータスPublished - 2016 4 1
外部発表はい

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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