The phage-shock-protein (Psp) system is essential for Yersinia enterocolitica virulence. Mislocalized secretins induce psp gene expression, and kill psp null strains. We used transposon mutagenesis to investigate whether other genes are required to tolerate secretin-induced stress. Our motivation included the possibility of identifying signal transducers required to activate psp gene expression. Besides Psp, only defects in the RpoE system and the TrkA potassium transporter caused secretin sensitivity. These mutations did not cause the same specific/severe sensitivity as defects in the Psp system, nor did they affect psp gene expression. The Escherichia coli Psp system was reported to be induced via the ArcB redox sensor and to activate anaerobic metabolism. Our screen did not identify arcB, or any genes involved in anaerobic metabolism/regulation. Therefore, we investigated the role of ArcB in Y. enterocolitica and E. coli. ArcB was not required for secretin-dependent induction of psp gene expression. Furthermore, microarray analysis uncovered a restricted transcriptional response to prolonged secretin stress in Y. enterocolitica. Taken together, these data do not support the proposal that the Psp system is induced via ArcB and activates anaerobic metabolism. Rather, they suggest that Psp proteins may sense an inducing trigger and mediate their physiological output(s) directly.