Burkholderia pseudomallei, the causative agent of melioidosis, can be isolated from soil and water. To persist, adapt and survive within and outside their human host, bacteria rely on regulatory mechanisms that allow them to respond rapidly to stressful situations. We have examined the possible role of B. pseudomallei alternative sigma factor sigma(E) (RpoE) in the stress response and found that rpoE and its putative regulators (bprE-rseB-mucD) are transcribed in a single transcriptional unit. Inactivation of the rpoE operon changed the B. pseudomallei phenotype. Changes included increased susceptibility to killing by menadione and H(2)O(2), susceptibility to high osmolarity, reduced ability to form biofilms, and reduced survival in macrophage J774A.1. Therefore, we conclude that rpoE controls gene expression that contributes, at least in part, to B. pseudomallei adaptation to adverse environmental conditions.