Skip to main content


Peptide lineup against Gram-negative bacterial infection – first-in-class peptide inhibitor of H. pylori HtrA

Article metrics

  • 860 Accesses

More than 50% of the world population is infected with Helicobacter pylori (H. pylori) and the actual H. pylori treatments fail with increased regularity because of continuously rising antibiotic resistances. To meet this challenge, we focus on the development of a new anti-infective therapy against H. pylori by targeting a secreted enzyme, high temperature requirement A (HtrA). Release of the serine protease HtrA near the host’s gastric epithelial cells leads to loss of cellular adhesion due to E- cadherin cleavage [1]. We investigated the substrate cleavage sites of HtrA in its natural substrate E-cadherin performing a label-free mass spectrometry-based proteomic analysis and identified preferred cleavage positions by Edman sequencing. Further, we developed the first HtrA peptide inhibitor by synthesizing cleavage site fragments and analogues. Surface plasmon resonance (SPR) was used to perform binding studies. In vitro substrate cleavage assays as well as cellular infection assays fully support the biophysical data.


  1. 1.

    Hoy B, Löwer M, Weydig C, Carra G, Tegtmeyer N, Geppert T, Schröder P, Sewald N, Backert S, Schneider G, Wessler S: EMBO Rep. 2010, 11: 798-804. 10.1038/embor.2010.114.

Download references

Author information

Correspondence to Anna M Perna.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article


  • Surface Plasmon Resonance
  • Peptide Inhibitor
  • Gastric Epithelial Cell
  • Cleavage Assay
  • Substrate Cleavage