Regardless of oxygen availability, Bacillus subtilis is able to survive by maintaining highly regulated and coordinated metabolic pathways, with activation or repression of target genes and/or modulation of protein activity. The ResDE two-component regulatory system of B. subtilis controls gene expression globally at the transcriptional level in order to allow for either aerobic respiration or anaerobic nitrate respiration. Our long-term research goal is to understand how ResD is able to respond to various environmental signals including oxygen and NO and display altered transcriptional regulation depending on the presence of and interactions with RNA polymerase (RNAP) and other transcription factors (TFs). A major aim of this work is to further current understanding of the mechanistic and functional interactions between ResD and another RNAP-associated TF, Spx, under nitrate respiration conditions. B. subtilis relies on the global transcriptional regulator, Spx, to exert both positive and negative control over transcription initiation in response to oxidative stress. ResD and Spx likely coordinate interactions with RNAP in a manner that supports growth under aerobic or anaerobic conditions as the two TFs function under opposite physiological conditions in terms of oxygen levels.