Sulfane Sulfur Is a Strong Inducer of the Multiple Antibiotic Resistance Regulator MarR in Escherichia coli.

Luying Xun,Huaiwei Liu,Yongzhen Xia,Guanhua Xuan,Huangwei Xu

doi:10.3390/antiox10111778

Luying Xun, Huaiwei Liu + Show 3 more

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https://doi.org/10.3390/antiox10111778

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Abstract

Sulfane sulfur, including persulfide and polysulfide, is produced from the metabolism of sulfur-containing organic compounds or from sulfide oxidation. It is a normal cellular component, participating in signaling. In bacteria, it modifies gene regulators to activate the expression of genes involved in sulfur metabolism. However, to determine whether sulfane sulfur is a common signal in bacteria, additional evidence is required. The ubiquitous multiple antibiotic resistance regulator (MarR) family of regulators controls the expression of numerous genes, but the intrinsic inducers are often elusive. Recently, two MarR family members, Pseudomonas aeruginosa MexR and Staphylococcus aureus MgrA, have been reported to sense sulfane sulfur. Here, we report that Escherichia coli MarR, the prototypical member of the family, also senses sulfane sulfur to form one or two disulfide or trisulfide bonds between two dimers. Although the tetramer with two disulfide bonds does not bind to its target DNA, our results suggest that the tetramer with one disulfide bond does bind to its target DNA, with reduced affinity. An MarR-repressed mKate reporter is strongly induced by polysulfide in E. coli. Further investigation is needed to determine whether sulfane sulfur is a common signal of the family members, but three members sense cellular sulfane sulfur to turn on antibiotic resistance genes. The findings offer additional support for a general signaling role of sulfane sulfur in bacteria.

Highlights

multiple antibiotic resistance regulator (MarR) from E. coli MG1655 was overproduced in E. coli BL21 with a N-terminal His-tag and subsequently purified
The findings are consistent with previous reports that MarR forms dimers, tetramers, and higher multimers with target DNA probes [25,32]
H2 Sn treatment significantly decreased MarR’s affinity to its DNA probe, and a complete shift of the probe occurred with higher H2 Sn -treated MarR at

Summary

Introduction

Sulfane sulfur is a common cellular component, and it exists in several forms, including hydrogen polysulfide (H2 Sn , n ≥ 2), organic polysulfide (RSSn H, RSSn R, n ≥ 2), and elemental sulfur (S8 ) [1,2]. Cellular sulfane sulfur is produced from sulfide Excessive sulfane sulfur is removed either by enzymes, including persulfide dioxygenase [8], thioredoxin, and glutaredoxin [9], or by chemical reduction to H2 S with cellular thiols like glutathione [10]. Cellular sulfane sulfur in bacteria is maintained in a micromolar range, changing with growth phases and likely regulating biological behaviors associated with growth phases [2,12]

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