DNA Backbone Sulfur-Modification Expands Microbial Growth Range under Multiple Stresses by its anti-oxidation function

Yan Yang,Jingdan Liang,Zhijun Wang,Zixin Deng,Ying He,Xiang Xiao,Hui Li,Lei Xiong,Douglas Bartlett,Guanpeng Xu

doi:10.1038/s41598-017-02445-1

Abstract

DNA phosphorothioate (PT) modification is a sulfur modification on the backbone of DNA introduced by the proteins DndA-E. It has been detected within many bacteria isolates and metagenomic datasets, including human pathogens, and is considered to be widely distributed in nature. However, little is known about the physiological function of this modification, and thus its evolutionary significance and application potential remains largely a mystery. In this study, we focused on the advantages of DNA PT modification to bacterial cells coping with environmental stresses. We show that the mesophile Escherichia coli and the extremophile Shewanella piezotolerans both expanded their growth ranges following exposure to extreme temperature, salinity, pH, pressure, UV, X-ray and heavy metals as a result of DNA phophorothioation. The phophorothioated DNA reacted to both H2O2 and hydroxyl radicals in vivo, and protected genomic DNA as well as sensitive enzymes from intracellular oxidative damage. We further demonstrate that this process has evolved separate from its associated role in DNA restriction and modification. These findings provide a physiological role for a covalent modification widespread in nature and suggest possible applications in biotechnology and biomedicine.

Highlights

Modifications of DNA and RNA are involved in many physiological processes, including restriction-modification (R-M) systems and epigenetic control of DNA replication, transcription and translation[1]
We propose that PT modification may play a role in microbial adaptation to many extreme conditions because many PT modification strains were isolated from environments with different stresses and our previous study shows that a PT modification strain exhibited advantageous antioxidation properties[18]
We have discovered that the PT modification system can scavenge hydrogen peroxide and hydroxyl radicals in vivo and protect both genomic DNA and proteins from oxidative damage

Summary

Introduction

Modifications of DNA and RNA are involved in many physiological processes, including restriction-modification (R-M) systems and epigenetic control of DNA replication, transcription and translation[1]. DNA phosphorothioate (PT) modification is a novel modification on the DNA backbone, in which a non-bridging oxygen atom is swapped with a sulfur atom. It is a sequence-selective, stereospecific post-replicative modification governed by a family of proteins encoded by five genes, termed dnd (corresponding to the often-observed DNA degradation phenotype during electrophoresis)[2, 3]. About 86 PT modification strains possess these restriction gene homologues and www.nature.com/scientificreports/. About 125 strains lack the restriction system, indicating that dnd-encoded PT modifications provides functions other than R-M17. This hypothesis was first tested in an E. coli strain, and later extended to a deep-sea extremophilic bacterial strain

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