Isabell Asche

Suche


B10 Molecular function and signal transduction of the serine protease HtrA, a novel secreted effector protein of bacterial pathogens

Principal investigator
Steffen Backert

Mentor
Anja Lührmann

Interaction of enteric pathogens with the polarized epithelium: Role of bacterial and host factors for colonization, transmigration and disease development

In mammals, the epithelial cell layer of mucosal surfaces is an important barrier to prevent microbial entry into deeper tissues. Various pathogenic bacteria, however, have developed mechanisms to overcome this barrier. The gastric pathogen Helicobacter pylori (Hp) and the food borne pathogen Campylobacter jejuni (Cj) are such examples. Both pathogens can transmigrate across the intestinal epithelial cells during infection in vivo and in vitro. A potential virulence factor which is secreted by Hp and Cj to facilitate the crossing of the barrier is the serine protease HtrA (high-temperature requirement A). HtrA has been shown to be secreted by the bacteria and can cleave the adherence junctional protein E-cadherin to open the cell-to-cell junctions (Hoy et al. 2010, EMBO reports 11, 798; Böhm et al. 2012, Gut Pathog. 25, 3). Another major virulence factor of Hp is the cytotoxin-associated antigen A (cagA). CagA is injected into host cells by a type IV secretion system (T4SS) and has multiple effects on epithelial cells. An example is the potential to perturb cell polarity. It has been shown that the T4SS requires a host cell receptor for functioning (Kwok et al. 2007, Nature 449, 862). This receptor was identified as the integrin member α5β1. Interestingly, this and other integrin members are basal receptors of epithelial cells and normally not present at apical surfaces. Thus, it is yet unclear if CagA is injected from apical and / or basal surfaces. The aim of this study is to investigate the interplay between HtrA and T4SS to inject CagA using modern microscopic and signaling techniques.

.

Figure: Confocal laser scanning microscopy image of MDCK cells expressing mRFP-Ecadherin (red) infected with GFP-Hp (green).

 

Publications

 

 

Presentations

October 2016

8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany
”Interaction of Helicobacter pylori with host cells and type IV secretion of CagA”

Poster
     
October 2015

2nd International SFB 796 Conference: Mechanisms of microbial host cell manipulation: From plants to humans, Erlangen, Germany
Interaction of Helicobacter pylori and Campylobacter jejeuni with cell-to-cell junctions in polarized epithelial cells

Poster
     
July 2015

7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany
”Interaction of Helicobacter pylori and Campylobacter jejeuni with cell-to-cell junctions in polarized epithelial cells”

Talk
     
July 2014

6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
“Role of the serine protease HtrA in transmigration of bacterial pathogens across polarized epithelial cells”

Talk
     

Awards

Best Poster Award

First place

8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany, October 2016
“Interaction of Helicobacter pylori with host cells and type IV secretion of CagA“