Inactivation of dsbA (disulfide bond formation), either by an insertion (Sh4, dsbA::kan) or by alteration of the active site (Sh42, dsbA33G), renders Shigella flexneri avirulent. However, Sh4 and Sh42 behave differently in many ways in vitro and in vivo. A gene of unknown function, yihE, up-stream and cotranscribed with dsbA, is thought to differentiate Sh4 and Sh42 as the kan insertion may result in a truncated unstable yihE-dsbA mRNA in Sh4. To gain insight into the function of yihE, DNA array hybridization was performed to study the genomic expression in Sh4, Sh42, and a newly constructed yihE mutant (Sh54). Compared to the wild-type, M90TS, Sh4, and Sh54 demonstrated significantly changed transcription levels of about 100 genes, of which many involved in energy metabolism and stress response were down- and up-regulated, respectively. In contrast, Sh42 showed altered transcription levels of only 20 genes. The results argue that yihE is principally responsible for the changed genomic expression in Sh4 and Sh54. Given the fact that the transcription of yihE-dsbA is regulated by the CpxRA two-component signal transduction system, yihE is probably involved in the extracytoplasmic stress response in a manor deserving further studies.