Mechanism of HS-mediated protection against oxidative stress in .

Endogenous hydrogen sulfide (HS) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous HS in Cellular resistance to HO strongly depends on the activity of , a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆ cells hypersensitive to HO Conversely, induction of chromosomal from a strong pLtetO-1 promoter (P -) renders ∆ cells fully resistant to HO Furthermore, the endogenous level of HS is reduced in ∆ or ∆ ∆ cells but restored after the addition of an iron chelator dipyridyl. Using a highly sensitive reporter of the global response to DNA damage (SOS) and the TUNEL assay, we show that 3MST-derived HS protects chromosomal DNA from oxidative damage. We also show that the induction of the CysB regulon in response to oxidative stress depends on 3MST, whereas the CysB-regulated l-cystine transporter, TcyP, plays the principle role in the 3MST-mediated generation of HS. These findings led us to propose a model to explain the interplay between l-cysteine metabolism, HS production, and oxidative stress, in which 3MST protects against oxidative stress via l-cysteine utilization and HS-mediated sequestration of free iron necessary for the genotoxic Fenton reaction.