Mitotic Arrest-Deficient 2 Like 2 (MAD2L2) Interacts with Escherichia coli Effector Protein EspF.

Amin Tahoun,Hanem El-Sharkawy,Manfred Koegl,Arvind Mahajan,Lina Jamil M Abdel-Hafez,Samar M Moustafa,Juergen Haas,Ehab Kotb Elmahallawy,David L Gally,Ashraf Albrakati

doi:10.3390/life11090971

Abstract

Enteropathogenic (EPEC) and Enterohemorrhagic (EHEC) Escherichia coli are considered emerging zoonotic pathogens of worldwide distribution. The pathogenicity of the bacteria is conferred by multiple virulence determinants, including the locus of enterocyte effacement (LEE) pathogenicity island, which encodes a type III secretion system (T3SS) and effector proteins, including the multifunctional secreted effector protein (EspF). EspF sequences differ between EPEC and EHEC serotypes in terms of the number and residues of SH3-binding polyproline-rich repeats and N-terminal localization sequence. The aim of this study was to discover additional cellular interactions of EspF that may play important roles in E. coli colonization using the Yeast two-hybrid screening system (Y2H). Y2H screening identified the anaphase-promoting complex inhibitor Mitotic Arrest-Deficient 2 Like 2 (MAD2L2) as a host protein that interacts with EspF. Using LUMIER assays, MAD2L2 was shown to interact with EspF variants from EHEC O157:H7 and O26:H11 as well as EPEC O127:H6. MAD2L2 is targeted by the non-homologous Shigella effector protein invasion plasmid antigen B (IpaB) to halt the cell cycle and limit epithelial cell turnover. Therefore, we postulate that interactions between EspF and MAD2L2 serve a similar function in promoting EPEC and EHEC colonization, since cellular turnover is a key method for bacteria removal from the epithelium. Future work should investigate the biological importance of this interaction that could promote the colonization of EPEC and EHEC E. coli in the host.

Highlights

Introduction conditions of the Creative CommonsEnteropathogenic and Enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) constitute a significant major risk to human health worldwide [1]
We have shown differences between EPEC and EHEC resistance to phagocytosis that was attributed to the interaction of their EspF variants with SNX9 and neuronal Wiskott–Aldrich syndrome protein (N-WASP) using LUMIER binding assays [18]
The mating between the bait strain, containing EspF variants, and the prey strain, containing cDNA for a human protein library, suggested a new protein hit for EspF, with an interaction between EspF from EHEC O26:H11 and the host Mitotic Arrest-Deficient 2 Like 2 (MAD2L2) protein

Summary

Introduction

Enteropathogenic and Enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) constitute a significant major risk to human health worldwide [1]. Shiga-toxigenic E. coli (STEC) that are considered as a cause of potentially fatal foodborne infections, arising from animal-to-human infection, where cattle are considered the main reservoir host [7,8,9]. These emerging zoonotic pathogens are primarily found in industrialized countries and cause sporadic outbreaks of severe disease in humans, including hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) [10].

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