YcjW: a transcription factor that controls the emergency generator of H2S in E. coli.

Hydrogen sulfide (H2S) is a ubiquitous gaseous molecule that is endogenously produced in both eukaryotes and prokaryotes. Its role as a pleiotropic signaling molecule has been well characterized in mammals1,2. In contrast, the physiological role of H2S in bacteria only recently became apparent; H2S acts as a cytoprotectant against antibiotics-induced stress and affect the cells ability to maintain redox homeostasis 3-5. In E. coli, endogenous H2S production is primarily dependent on 3-mercaptopyruvate sulfurtransferase (3MST), encoded by mstA, previously known as sseA3,4. Here, we show that cells lacking 3MST acquired a unique phenotypic suppressor mutation resulting in compensatory H2S production and tolerance to antibiotics and oxidative stress. Using whole genome sequencing, we mapped a non-synonymous single nucleotide polymorphism (SNP) to uncharacterized Laci-type transcription factor, YcjW. We identified transcriptional regulatory targets of YcjW and discovered a major target, thiosulfate sulfurtransferase PspE, as an alternative mechanism for H2S biosynthesis. Deletion of pspE was sufficient to antagonize phenotypic suppression. Our results reveal a complex interaction between cell metabolism and H2S production and the role, a hithero uncharacterized transcription factor, YcjW, plays in linking the two.