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

Research output: Contribution to journalArticlepeer-review

Abstract

Enteropathogenic Escherichia coli (EPEC) is a primary human enteric bacterial pathogen causing acute diarrhea in children. EPEC colonizes the small intestine, and the disease is induced, in part, by the ability of the pathogen to utilize a type III secretion machinery to inject a battery of proteins, termed “effectors,” from the bacterial cytoplasm into the intestinal enterocytes. Host cell responses to the infecting pathogen are also essential for disease development. Despite intensive research, the mechanisms of EPEC infection and host cell responses need to be better understood. Here, we show that specific EPEC type III secreted effectors, EspF and Map, induce lytic host cell death and also lysosomal exocytosis (LE), resulting in the secretion of lysosomal enzymes into the extracellular environment and the appearance of the lysosomal membrane proteins, Lamp-1, on the infected cell surface. The mitochondrial cytotoxicity and the guanine nucleotide exchange factor domains of Map have been identified to be involved in these processes. In contrast, EspZ, an EPEC effector that protects against lytic cell death, also inhibits LE. Our results combined suggest that LE and host cell death are tightly interconnected processes. The mechanisms and functional significance of these processes on EPEC infection are discussed.

Original languageEnglish
Article number01979-23
JournalmBio
Volume14
Issue number6
Early online date1 Dec 2023
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 Shtuhin-Rahav et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Funding

R.S.-R, E.A.B., and I.N. are the recipients of Dr. Willem Been Legacy Fellowship. This research was supported by the Israel Science Foundation (grant no. 1671/19). We thank very much Prof. Luis Angel Fernandez (Centro Nacional de Biotecnología, CNB-CSIC, Madrid, Spain) for the gift of EPEC1 and EPEC2 strains and Prof. Ilan Rosenshine (Hadassah Medical School, The Hebrew University of Jerusalem) for providing EPEC strains and inspiring discussions. We thank Prof. Norma W. Andrews (University of Maryland) for helpful discussions and help in establishing the lysosomal exocytosis assays in our lab. R.S.-R, E.A.B., and I.N. are the recipients of Dr. Willem Been Legacy Fellowship. This research was supported by the Israel Science Foundation (grant no. 1671/19). Israel Science Foundation (ISF) Benjamin Aroeti

FundersFunder number
Benjamin Aroeti
Hadassah Medical School
University of Maryland
Hebrew University of Jerusalem
Israel Science Foundation1671/19
Centro Nacional de Biotecnología

    Keywords

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

    Fingerprint

    Dive into the research topics of 'Enteropathogenic E. coli infection co-elicits lysosomal exocytosis and lytic host cell death'. Together they form a unique fingerprint.

    Cite this