This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Knappstein, S.
Right arrow Articles by Heusipp, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Knappstein, S.
Right arrow Articles by Heusipp, G.

 Previous Article  |  Next Article 

Infection and Immunity, August 2004, p. 4344-4350, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4344-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

{alpha}1-Antitrypsin Binds to and Interferes with Functionality of EspB from Atypical and Typical Enteropathogenic Escherichia coli Strains

Sabine Knappstein, Tina Ide, M. Alexander Schmidt,* and Gerhard Heusipp

Institut für Infektiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universitätsklinikum Münster, 48149 Münster, Germany

Received 8 January 2004/ Returned for modification 10 February 2004/ Accepted 6 May 2004

Enteropathogenic Escherichia coli (EPEC), including diffusely adhering atypical E. coli, strains use a type III secretion system to deliver effector proteins into the membrane and cytoplasm of infected cells. The E. coli secreted proteins A, B, and D (EspA, EspB, and EspD) are required for the formation of the characteristic attaching and effacing (A/E) lesions. EspB and EspD are thought to form a translocation pore in the host cell membrane through which effector proteins are injected into the host cytosol. Besides its function in pore formation, EspB has been found in the cytosol and implicated to function as an effector protein. We screened for putative host cell proteins interacting with EspB of atypical EPEC strains and identified {alpha}1-antitrypsin (AAT) as a binding partner for EspB. AAT binds to EspB in pull-down and overlay experiments and also to EspD in overlay experiments. In agreement with the role of EspB and EspD in pore formation, EPEC-mediated hemolysis of red blood cells is strongly reduced by AAT in a concentration-dependent manner, indicating that AAT interferes with type III secretion by inhibiting the formation of the translocation pore. This is further supported by a decreased actin polymerization after infection of HeLa or CaCo-2 cells with EPEC in the presence of physiologically relevant concentrations of AAT. In this study, we identify AAT as a new binding partner for EspB and EspD, suggesting a previously unappreciated role for AAT in host cell defense against EPEC infections and potentially also against other bacterial pathogens.

* Corresponding author. Mailing address: ZMBE, Institut für Infektiologie, von-Esmarch-Str. 56, 48149 Münster, Germany. Phone: 49-251-8356466. Fax: 49-251-8356467. E-mail: infekt{at}uni-muenster.de.

Editor: J. B. Bliska

Infection and Immunity, August 2004, p. 4344-4350, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4344-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Manolov, T., Tan, T. T., Forsgren, A., Riesbeck, K. (2008). Moraxella-Dependent {alpha}1-Antichymotrypsin Neutralization: A Unique Virulence Mechanism. Am. J. Respir. Cell Mol. Bio. 38: 609-617 [Abstract] [Full Text]  
  • Janciauskiene, S. M., Nita, I. M., Stevens, T. (2007). {alpha}1-Antitrypsin, Old Dog, New Tricks: {alpha}1-ANTITRYPSIN EXERTS IN VITRO ANTI-INFLAMMATORY ACTIVITY IN HUMAN MONOCYTES BY ELEVATING cAMP. J. Biol. Chem. 282: 8573-8582 [Abstract] [Full Text]  
  • Heusipp, G., Spekker, K., Brast, S., Falker, S., Schmidt, M. A. (2006). YopM of Yersinia enterocolitica specifically interacts with {alpha}1-antitrypsin without affecting the anti-protease activity.. Microbiology 152: 1327-1335 [Abstract] [Full Text]  
  • Sharma, R., Tesfay, S., Tomson, F. L., Kanteti, R. P., Viswanathan, V. K., Hecht, G. (2006). Balance of bacterial pro- and anti-inflammatory mediators dictates net effect of enteropathogenic Escherichia coli on intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G685-G694 [Abstract] [Full Text]  
  • Luo, W., Donnenberg, M. S. (2006). Analysis of the Function of Enteropathogenic Escherichia coli EspB by Random Mutagenesis. Infect. Immun. 74: 810-820 [Abstract] [Full Text]  
  • Chiu, H.-J., Syu, W.-J. (2005). Functional analysis of EspB from enterohaemorrhagic Escherichia coli. Microbiology 151: 3277-3286 [Abstract] [Full Text]  
  • Garmendia, J., Frankel, G., Crepin, V. F. (2005). Enteropathogenic and Enterohemorrhagic Escherichia coli Infections: Translocation, Translocation, Translocation. Infect. Immun. 73: 2573-2585 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»