The extracellular death factor (EDF) protects Escherichia coli by scavenging hydroxyl radicals induced by bactericidal antibiotics.

Wenjie Zhai,Yuanming Qi,Mingxia Zhai,Yanfeng Gao,Zhongyi Yan,Guodong Li

doi:10.1186/s40064-015-0968-9

Abstract

The newly discovered extracellular death factor (EDF) is a pentapeptide with the sequence NNWNN in Escherichia coli. It was reported that it participated in the cell death process mediated by toxin-antitoxin system mazEF. Reactive oxygen species (ROS) are recently considered as common factors for bactericidal antibiotics-mediated cell death. Previous study indicated that EDF could scavenge hydroxyl radicals and might act as a signal molecule with dual effects, “death” and “survival”. But the structure-activity relationship of EDF and the effects of EDF on the activity of antibiotics remain unclear. In the present study, our results indicated that tryptophan could be the key residue to the hydroxyl radicals-scavenging activity of EDF, and EDF could protect Escherichia coli from killing by bactericidal antibiotics, but not by DNA-damaging or bacteriostatic antibiotics. Our results could provide novel evidence to understand the role of EDF in drug-resistance.

Highlights

The Extracellular Death Factor (EDF) with the sequence NNWNN (Asn-Asn-Trp-Asn-Asn-OH) was discovered by Kolodkin-Gal and colleagues in 2007 (Kolodkin-Gal et al 2007)
In order to identify the key residue of EDF to elicit this activity, EDF and its mutants were synthesized by using glycinescanning strategy, and their hydroxyl-radicals scavenging activity was studied
We investigated the effects of EDF on the bactericidal antibiotic, ampicillin, which could make bacteria produce hydroxyl radicals and lead to cell death (Walsh 2003; Kolodkin-Gal and Engelberg-Kulka 2008)

Summary

Introduction

The Extracellular Death Factor (EDF) with the sequence NNWNN (Asn-Asn-Trp-Asn-Asn-OH) was discovered by Kolodkin-Gal and colleagues in 2007 (Kolodkin-Gal et al 2007). EDF is the first peptidic molecule involved in the quorum-sensing of E. coli. It is different from the classical peptidic quorum-sensing molecules among gram-positive bacteria because that it is derived from an enzyme, glucose-6-phosphate dehydrogenase (KolodkinGal et al 2007; Kolodkin-Gal and Engelberg-Kulka 2008). EDF and the classical toxin-antitoxin system mazEF could determine the programmed cell death (PCD) mode of some bacteria induced by antibiotics (Kolodkin-Gal et al 2008). It was reported that EDF could inhibit the formation of the MazEF complex, and enhance the endoribonucleolytic activity of MazF (Belitsky et al 2011). The toxin MazF could lead to the PCD of the major population of E. coli (Amitai et al 2009)

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Discussion

Conclusion