Sinorhizobium meliloti genes transcriptionally up-regulated after heat stress, as well as upon entry into stationary phase, were identified by microarray analyses. Sixty stress response genes were thus found to be up-regulated under both conditions. One of them, rpoE2 (smc01506), encodes a putative extracytoplasmic function (ECF) sigma factor. We showed that this sigma factor controls its own transcription and is activated by various stress conditions, including heat and salt, as well as entry into stationary phase after either carbon or nitrogen starvation. We also present evidence that the product of the gene cotranscribed with rpoE2 negatively regulates RpoE2 activity, and we therefore propose that it plays the function of anti-sigma factor. By combining transcriptomic, bioinformatic, and quantitative reverse transcription-PCR analyses, we identified 44 RpoE2-controlled genes and predicted the number of RpoE2 targets to be higher. Strikingly, more than one-third of the 60 stress response genes identified in this study are RpoE2 targets. Interestingly, two genes encoding proteins with known functions in stress responses, namely, katC and rpoH2, as well as a second ECF-encoding gene, rpoE5, were found to be RpoE2 regulated. Altogether, these data suggest that RpoE2 is a major global regulator of the general stress response in S. meliloti. Despite these observations, and although this sigma factor is well conserved among alphaproteobacteria, no in vitro nor in planta phenotypic difference from the wild-type strain could be detected for rpoE2 mutants. This therefore suggests that other important actors in the general stress response have still to be identified in S. meliloti.To survive the many stress conditions that they encounter in nature, bacteria have evolved rapid responses that result in the prevention or repair of cellular damages caused by stresses. In addition to these usually stress-specific responses, more general stress responses take place in reaction to a variety of insults as different as high osmolarity, heat or cold shock, pH variation, and nutrient starvation (which results in stationary phase). One well-known consequence of these general stress responses is the ability of bacteria to resist stress better in stationary phase than in exponential phase. This phenomenon, observed in most bacterial species studied so far, is considered a universal way for these microorganisms to survive not only the stress that they currently experience, but also stress conditions that they could potentially face in the future, and is therefore of primary importance in nature, where bacteria often are nutrient or oxygen limited and where environmental conditions constantly change (28).Much of our knowledge regarding the mechanisms of induction of general stress responses derives from studies of the model bacterium Escherichia coli and its close relatives. In these bacteria, entry into stationary phase, as well as a number of different stress conditions, leads to the activation of alternative sigma factors, which re...