Safeguarding intestine cells against enteropathogenic Escherichia coli by intracellular protein reaction, a preventive antibacterial mechanism

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Jiaming Qiu
  • Yunyu Nie
  • Yuan Zhao
  • Yu Zhang
  • Linting Li
  • Rui Wang
  • Miaomiao Wang
  • Jianhao Wang
  • Yong-Qiang Li
  • Jiang Xia

Detail(s)

Original languageEnglish
Pages (from-to)5260-5268
Journal / PublicationProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number10
Online published24 Feb 2020
Publication statusPublished - 10 Mar 2020

Abstract

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic Escherichia coli (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism.

Research Area(s)

  • site-specific protein reaction, Nck, peptide inhibitor, EPEC, bacterial infection, ACTIN PEDESTAL FORMATION, TERMINAL SH3 DOMAIN, N-WASP, PEPTIDE, TIR, EPIDEMIOLOGY, CONJUGATION, RESISTANCE, INVASION

Citation Format(s)

Safeguarding intestine cells against enteropathogenic Escherichia coli by intracellular protein reaction, a preventive antibacterial mechanism. / Qiu, Jiaming; Nie, Yunyu; Zhao, Yuan; Zhang, Yu; Li, Linting; Wang, Rui; Wang, Miaomiao; Chen, Sheng; Wang, Jianhao; Li, Yong-Qiang; Xia, Jiang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 10, 10.03.2020, p. 5260-5268.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal