Starvation of Salmonella enterica serovar Typhimurium (S. Typhimurium) for an exogenous source of carbon and energy (C-starvation) induces the starvation-stress response (SSR). The SSR functions to (i) maintain viability during long-term C-starvation and (ii) generate cross-resistance to other environmental stresses. The SSR is, at least partially, under the control of the alternative sigma factor, sigma(S). It is hypothesized that C-starvation causes cell envelope stresses that could induce the sigma(E) and/or Cpx regulons, both of which control extracytoplasmic functions and, thus, may play a role in the regulation of the SSR. In support of this hypothesis, Western blot analysis showed that the relative levels of sigma(E) increased during C-starvation, peaking after approximately 72 h of C-starvation; in contrast, CpxR levels remained relatively constant from exponential phase up to 72 h of C-starvation. To determine if sigma(E), and thus the regulon it controls, is an essential component of the SSR, several mutant strains were compared for their abilities to survive long-term C-starvation and to develop C-starvation-induced (CSI) cross-resistances. An rpoE mutant strain was significantly impaired in both long-term C-starvation survival (LT-CSS) and in CSI cross-resistance to challenges with 20 mM H(2)O(2) for 40 min, 55 degrees C for 16 min, pH 3.1 for 60 min and 870.2 USP U polymyxin B ml(-1) (PmB) for 60 min, to varying degrees. These results suggest that C-starvation can generate signals that induce the rpoE regulon and that one or more members of the sigma(E) regulon are required for maximal SSR function. Furthermore, evidence suggests that the sigma(E) and sigma(S) regulons function through separate mechanisms in the SSR. In contrast, C-starvation does not appear to generate signals required for Cpx regulon induction which support the findings that it is not required for LT-CSS or cross-resistance to H(2)O(2), pH 3.1 or PmB challenges. However, it was required to achieve maximal cross-resistance to 55 degrees C. Therefore, sigma(E) is a key regulatory component of the SSR and represents an additional sigma factor required for the SSR of Salmonella.