Enteropathogenic E. coli Hijacks Programmed Host‐Cell Death Pathways by Interfering with the Higher Order Oligomerization of Immune System Proteins

Abstract

During an infection, pathogens operate by hijacking or promoting crucial intracellular pathways within their hosts. In the case of Enteropathogenic Escherichia coli (EPEC) infection, bacterial proteins interact with host proteins to alter programmed cell death pathways. Recently, it has been found that many proteins from the immune system polymerise to transduce these death signals, forming higher order assembly structures.The aim of this project is to study how EPEC effector proteins interfere with the higher order assembly of immune proteins involved in signal transduction in inflammation, apoptosis and cell survival pathways.A selection of immune system proteins involved in signal transduction in different cell pathways was chosen to perform an in vitro screen against EPEC effector proteins by confocal spectroscopy. It was observed that espF (a bacterial effector protein) was able to change TRAF2 oligomerization/aggregation propensity. TRAF2 is a cytosolic protein involved in signal transduction in the cell death pathway. In cases of infection or stress, the protein forms higher order assembly structures to transduce the signal downstream. Further experiments performed in HeLa cells transfected with TRAF2 showed an increase in these structures in stressed cells when compared with the control group. When espF and TRAF2 were co‐transfected, co‐localization of both proteins was observed in distinct punctate intracellular structures reminiscent of higher order assemblies, together with other changes that are still under investigation.The bacterial protein espF appears to be hijacking the cell death pathway when there is an EPEC infection by avoiding TRAF2 self‐aggregation. Understanding precisely this host‐pathogen interaction could give us information useful for future drug development against EPEC infection.Support or Funding InformationEMBL Australia, University International Postgraduate Award (UIPA), University of New South WalesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.