A cytochrome repressed by a MarR family regulator confers resistance to metals, nitric oxide, sulfide, and cyanide in .

Unlabelled: is a ubiquitous environmental pathogen. Despite its remarkable adaptability, little is known about the mechanisms of stress resistance in this bacterium. Here, in a screen for iron-susceptible transposon mutants, we identified a cytochrome that protects against multiple stresses. The two subunits of this cytochrome (CioAB) are encoded by the operon, which also encodes a GbsR-type MarR family transcription factor (CioR). A ∆ mutant strain was sensitive to iron and the iron-requiring antibiotic streptonigrin and showed a decrease in siderophore production. Growth curves and survival assays revealed that the ∆ strain was also sensitive to zinc, hydrogen peroxide, nitric oxide, sulfide, and cyanide. Expression analysis showed that the promoter activity of the operon and the transcript levels of the genes were increased in a ∆ mutant. CioR bound the promoter region of the operon , indicating that CioR is a direct repressor of its own operon. Expression of the operon increased at high cell density and was dependent on the quorum-sensing regulator CviR. As cyanide is also a signal for expression, and production of endogenous cyanide is known to be a quorum sensing-regulated trait in , we suggest that CioAB is a cyanide-insensitive terminal oxidase that allows respiration under cyanogenic growth conditions. Our findings indicate that the cytochrome CioAB protects against multiple stress agents that are potentially produced endogenously or during interactions with a host.

Importance: The terminal oxidases of bacterial respiratory chains rely on heme-copper (heme-copper oxidases) or heme (cytochrome ) to catalyze the reduction of molecular oxygen to water. is a facultative anaerobic bacterium that uses oxygen and other electron acceptors for respiration under conditions of varying oxygen availability. The genome encodes multiple respiratory terminal oxidases, but their role and regulation remain unexplored. Here, we demonstrate that CioAB, the single cytochrome from , protects this bacterium against multiple stressors that are inhibitors of heme-copper oxidases, including nitric oxide, sulfide, and cyanide. CioAB also confers resistance to iron, zinc, and hydrogen peroxide. This cytochrome is encoded by the operon, which is under direct repression by the MarR-type regulator CioR. In addition, the operon responds to quorum sensing and to cyanide, suggesting a protective mechanism of increasing CioAB in the setting of high endogenous cyanide production.