Interaction of RTX toxins with the host cell plasma membrane

Feby M. Chacko; Lutz Schmitt

doi:10.1515/hsz-2022-0336

Article

Interaction of RTX toxins with the host cell plasma membrane

Feby M. Chacko

Feby M. Chacko did her integrated bachelor’s and master’s degree in Biology and Chemistry from Indian Institute of Science Education and Research, Thiruvananthapuram. For her master’s thesis, she screened for membrane fission catalysts in bacterial cells using Supported Membrane Tube (SMrT) assay system. After her graduation in 2019 from India, she moved to Germany in 2020 and started pursuing her PhD in Institute of Biochemistry, Heinrich Heine University Düsseldorf. Her work focused on the mechanism of RTX toxins.
and Lutz Schmitt

Lutz Schmitt did his master’s in Chemistry at the University of Freiburg and obtained his PhD from the Technical University Munich. After a Post Doc at Stanford University, he moved as a DFG-funded Emmy Noether fellow to the University of Marburg and University of Frankfurt. In 2005 he was appointed as Professor of Biochemistry at Heinrich Heine University Düsseldorf. His research interest are recognition processes at membranes and transport across membranes with an emphasis on ABC transporters.

Published/Copyright: March 14, 2023

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From the journal Biological Chemistry Volume 404 Issue 7

Abstract

Repeats in ToXins (RTX) protein family is a group of exoproteins secreted by Type 1 secretion system (T1SS) of several Gram-negative bacteria. The term RTX is derived from the characteristic nonapeptide sequence (GGxGxDxUx) present at the C-terminus of the protein. This RTX domain binds to calcium ions in the extracellular medium after being secreted out of the bacterial cells, and this facilitates folding of the entire protein. The secreted protein then binds to the host cell membrane and forms pores via a complex pathway, which eventually leads to the cell lysis. In this review, we summarize two different pathways in which RTX toxins interact with host cell membrane and discuss the possible reasons for specific and unspecific activity of RTX toxins to different types of host cells.

Keywords: β2 integrins; cholesterol; CyaA; gangliosides; HlyA; pore forming

Corresponding author: Lutz Schmitt, Institute of Biochemistry, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany, E-mail: lutz.schmitt@hhu.de

Funding source: Jürgen Manchot Stiftung

Award Identifier / Grant number: MOI IV

About the authors

Feby M. Chacko

Feby M. Chacko did her integrated bachelor’s and master’s degree in Biology and Chemistry from Indian Institute of Science Education and Research, Thiruvananthapuram. For her master’s thesis, she screened for membrane fission catalysts in bacterial cells using Supported Membrane Tube (SMrT) assay system. After her graduation in 2019 from India, she moved to Germany in 2020 and started pursuing her PhD in Institute of Biochemistry, Heinrich Heine University Düsseldorf. Her work focused on the mechanism of RTX toxins.

Lutz Schmitt

Lutz Schmitt did his master’s in Chemistry at the University of Freiburg and obtained his PhD from the Technical University Munich. After a Post Doc at Stanford University, he moved as a DFG-funded Emmy Noether fellow to the University of Marburg and University of Frankfurt. In 2005 he was appointed as Professor of Biochemistry at Heinrich Heine University Düsseldorf. His research interest are recognition processes at membranes and transport across membranes with an emphasis on ABC transporters.

Acknowledgements

We thank all current and former members of the Institute of Biochemistry, the Center of Advanced Imaging (CAi), and the Center for Structural Studies (CSS), Heinrich Heine University Düsseldorf for support and stimulating discussions. Research on RTX toxins is supported by the Jürgen Manchot Graduate School “Molecules of Infections” (to L.S.).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was financially supported by the Jürgen Manchot Stiftung (MOI IV).
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2022-11-28

Accepted: 2023-02-27

Published Online: 2023-03-14

Published in Print: 2023-06-27

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Keywords for this article

β2 integrins; cholesterol; CyaA; gangliosides; HlyA; pore forming