The two-component system ZraP-SR is a novel envelope stress response (ESR) system [2], and they are important to maintain membrane envelope integrity in the presence of biocides targeting the envelope [2]. ZraR also belongs to the group of σ⁵⁴-dependent transcriptional regulators [1]. Members of this group contain three domains: the sensory domain located in the N terminus, the central domain involved in ATP hydrolysis and interaction with σ⁵⁴, and the C-terminal domain, which contains a helix-turn-helix motif [3]. ZraR recognizes a DNA sequence of two inverted repeats of 17 bp separated by 12 bp [1]. ZraR regulator exhibits little sequence specificity. It provides a weak motif that appears with strong accuracy in a subset of regulated genes. The central A/T tract is characteristic of flexible regions that can be bent by the protein. ZraR binds regions located between divergently oriented genes and where negative supercoiling accumulates []. A regulatory role related to the activity of the enzyme hydrogenase 3 has been assigned to ZraR (previously called HydG) [3], but it was demonstrated that this regulation was nonspecific [1]. Based on a crystal structure of ZraR from Salmonella enterica serovar Typhimurium, it has been suggested that this protein may function as a dodecamer []. Transcription of zraR is induced by zinc stress [4] and high levels of c-di-GMP [5]. Deletion of ZraR confers increased susceptibility to five classes of antibiotics and to some environmental stresses targeting the envelope [2]. ZraR induction was optimally obtained with 500 M ZnSO₄, optimally expressed at an OD₆₀₀ of 0.6, and stably produced during both the exponential and stationary phases (OD = 1.5) [2].