Enteropathogenic E. coli infection co-elicits lysosomal exocytosis and lytic host cell death

Raisa Shtuhin-Rahav; Aaron Olender; Efrat Zlotkin-Rivkin; Etan Amse Bouman; Tsafi Danieli; Yael Nir-Keren; Aryeh M Weiss; Ipsita Nandi; Benjamin Aroeti

doi:10.1128/mbio.01979-23

Enteropathogenic E. coli infection co-elicits lysosomal exocytosis and lytic host cell death

mBio. 2023 Dec 1;14(6):e0197923. doi: 10.1128/mbio.01979-23. Online ahead of print.

Authors

Raisa Shtuhin-Rahav^{1

2}, Aaron Olender^{2

3}, Efrat Zlotkin-Rivkin^{1

2}, Etan Amse Bouman^{1

2}, Tsafi Danieli⁴, Yael Nir-Keren⁴, Aryeh M Weiss⁵, Ipsita Nandi^{1

2}, Benjamin Aroeti^{1

2}

Affiliations

¹ Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus-Givat Ram, Jerusalem, Israel.
² Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus-Givat Ram, Jerusalem, Israel.
³ The Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem, The Edmond J. Safra Campus-Givat Ram, Jerusalem, Israel.
⁴ The Protein Production Facility, Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem, The Edmond J. Safra Campus-Givat Ram, Jerusalem, Israel.
⁵ Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.

Abstract

Enteropathogenic Escherichia coli (EPEC) infection is a significant cause of gastroenteritis, mainly in children. Therefore, studying the mechanisms of EPEC infection is an important research theme. EPEC modulates its host cell life by injecting via a type III secretion machinery cell death modulating effector proteins. For instance, while EspF and Map promote mitochondrial cell death, EspZ antagonizes cell death. We show that these effectors also control lysosomal exocytosis, i.e., the trafficking of lysosomes to the host cell plasma membrane. Interestingly, the capacity of these effectors to induce or protect against cell death correlates completely with their ability to induce LE, suggesting that the two processes are interconnected. Modulating host cell death is critical for establishing bacterial attachment to the host and subsequent dissemination. Therefore, exploring the modes of LE involvement in host cell death is crucial for elucidating the mechanisms underlying EPEC infection and disease.

Keywords: EspF; EspZ; Map; cell death; enteropathogenic E. coli; host-pathogen interactions; lysosomal exocytosis; membrane repair; type III secreted effectors.