The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by performing physiological, global transcriptional, and metabolite analyses. Salt adaptation was reflected by increased expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). The expression of genes involved in carbon metabolism, cell growth, and phage structures was decreased. Transcriptome profiles of D. vulgaris responses to salt adaptation were compared with transcriptome profiles of D. vulgaris responses to salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate and alanine accumulated under salt adaptation conditions, suggesting that these amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium relieved salt-related growth inhibition. A conceptual model that links the observed results to currently available knowledge is proposed to increase our understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl levels.Desulfovibrio vulgaris Hildenborough is a member of the anaerobic sulfate-reducing bacteria (SRB) (46) that are ubiquitous in anaerobic environments containing sulfate (43), such as gas pipelines, subsurface metal tanks, sediments, and offshore oil production facilities (6, 63). These niches can also contain high concentrations of salt (e.g., NaCl). Because of its capacity to immobilize soluble forms of toxic metals, the potential of D. vulgaris for bioremediation has been widely recognized (35, 57). In addition, Desulfovibrio species have been found to reduce metals in sediments and soils with high concentrations of NaCl and a mixture of toxic metals (3) and to cope with salt stresses that result from environmental hydration-dehydration cycles. Therefore, further understanding of mechanisms that D. vulgaris uses to survive and adapt to environments with high concentrations of salt (e.g., NaCl) may contribute to the development of successful bioremediation strategies. Such knowledge might also be useful for prediction and control of metal biocorrosion given the apparent role of this microbe in corrosion.The response of a microorganism to high salinity can be divided into two phases. The initial reaction to a sudden increase in the salt concentration is termed "salt shock," while the subsequent survival and growth in a high-salinity environment can be termed "salt adaptation." In both cases, exposure of D. vulgaris to high salinity may present two different, but related, environmental stimuli; one of these stimuli is osmotic stress, and the other is ionic stress (19). Hyperosmotic stress triggers water efflux from the cell that results in a reduction in the turgor pressure and dehydration of the cytoplasm, which increases the ion concentration in the cytosol, whereas ionic stress ca...