dDespite the scientific and industrial importance of desiccation tolerance in Salmonella, knowledge regarding its genetic basis is still scarce. In the present study, we performed a transcriptomic analysis of dehydrated and water-suspended Salmonella enterica serovar Typhimurium using microarrays. Dehydration induced expression of 90 genes and downregulated that of 7 genes. Ribosomal structural genes represented the most abundant functional group with a relatively higher transcription during dehydration. Other main induced functional groups included genes involved in amino acid metabolism, energy production, ion transport, transcription, and stress response. The highest induction was observed in the kdpFABC operon, encoding a potassium transport channel. Knockout mutations were generated in nine upregulated genes. Five mutants displayed lower tolerance to desiccation, implying the involvement of the corresponding genes in the adaptation of Salmonella to desiccation. These included genes encoding the isocitrate-lyase AceA, the lipid A biosynthesis palmitoleoyl-acyltransferase Ddg, the modular iron-sulfur cluster scaffolding protein NifU, the global regulator Fnr, and the alternative sigma factor RpoE. Notably, these proteins were previously implicated in the response of Salmonella to oxidative stress, heat shock, and cold shock. A strain with a mutation in the structural gene kdpA had a tolerance to dehydration comparable to that of the parent strain, implying that potassium transport through this system is dispensable for early adaptation to the dry environment. Nevertheless, this mutant was significantly impaired in long-term persistence during cold storage. Our findings indicate the involvement of a relatively small fraction of the Salmonella genome in transcriptional adjustment from water to dehydration, with a high prevalence of genes belonging to the protein biosynthesis machinery. A s part of its life cycle Salmonella can persist outside the host where it is exposed to various stresses (73), with desiccation being one of the most common and significant ones. Salmonella can survive from several weeks to several years on dry surfaces (21, 36, 48), eggshells (55), almond kernels (68), pecans (11), and dry confectionery raw materials (47). During the last decade, Salmonella has been involved in several national and international outbreaks related to consumption of low-water-activity foods such as snacks, almonds, peanut butter, chocolate, and paprika (4,5,6,37,45,71).In spite of the scientific importance and the practical implications of desiccation tolerance in Salmonella, the exact mechanisms of its cellular adaptation to desiccation remain relatively poorly understood. Several studies have investigated desiccation tolerance in Salmonella. Extracellular components such as thin aggregative fimbriae and cellulose as well as the lipopolysaccharide (LPS) core unit are apparently required for optimal desiccation tolerance (28,29,72). Exposure of Salmonella to desiccation stress increased cross-tolerance to a numb...