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

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.

Genomic profiling of four cultivated Candidatus Nitrotoga spp. predicts broad metabolic potential and environmental distribution

“…The SPKER genome encoded a suite of genes responsible for DNA phosphorothionation (iscS, dndBCDE) (swapping a non-bridging oxygen atom for a sulfur atom) that could offer resistance to a related restriction-modification system (dptHGF) [101] found nearby on the genome. DNA phosphorothionation was recently found to expand microbial growth range under multiple stresses due to its intrinsic antioxidant function [102]. This ability may greatly expand the environments in which Ca.…”

Shewanella decolorationis LDS1 Chromate Resistance

“…The inability of S. decolorationis LDS1 to grow at low temperatures is noticeable. Indeed, it was established in Escherichia coli B7A and in Salmonella enterica serovar Cerro strain 87 that the restriction system is temperature dependent and is activated at 15°C (44). The temperature dependence of the restriction system in S. decolorationis LDS1 is yet to be determined, as is the role of that restriction system once activated.…”

“…The function of this M-R system is not well understood, and an additional role in the epigenetic control of gene expression is suspected (39). Indeed, the products of the dnd operon were shown to sustain bacterial growth under stresses like H 2 O 2 , heat, or salinity by protecting DNA from oxidative damage and restriction enzymes (44). In agreement with experiments done in Escherichia coli and Shewanella piezotolerans, our hypothesis is that the production of DndB through DndE proteins improves the growth of S. decolorationis LDS1 chromate (0.4 mM) (Fig.…”

An in vitro DNA phosphorothioate modification reaction

“…DNA PT modification occurs in bacteria, ranging from about 10% to 60% in different bacterial strains (Alonso et al, 2005;Wang et al, 2011Wang et al, , 2007Zhou et al, 2005). The incorporation of sulfur in this manner endows the PT-modified DNA with altered redox and nucleophilic properties (Xie et al, 2012), providing it a special ability to be involved in complicated biological functions, such as antioxidation, restriction modification, virus defense, gene transcriptional control and the maintenance of cellular redox homeostasis (Chen et al, 2017;Kellner et al, 2017;Ray, Mills, & Dyson, 1995;Tong et al, 2018;Wang, Jiang, Deng, Dedon, & Chen, 2018;Wu et al, 2017;Xie et al, 2012;Xiong et al, 2019;Xu, Yao, Zhou, Deng, & You, 2010;Yang et al, 2017).…”