Technical Abstract: Salmonella enterica, a bacterial, food-borne pathogen of humans, can contaminate raw fruits and vegetables. Causing much public concern, the bacteria can survive in water used to wash produce. The ability to survive the low-osmolarity of the wash waters is attributed to the OpgGH operon that leads to the production of osmotically-regulated periplasmic glucans. Mutants lacking OpgGH grow slowly under low-osmotic conditions, but there are also unexpected traits such as abnormal flagellar motility and reduced virulence in mice. To get a broader understanding of these pleiotropic effects, we examined the proteome of these mutants using high-throughput mass spectrometry. We identified approximately one third of the proteins encoded by the genome and used label-free spectral counting to determine the relative amounts of proteins in wild-type cultures and mutants. Mutants had reduced amounts of proteins required for osmotic sensing, flagellar motility, purine and pyrimidine metabolism, oxidative energy production and protein translation. By contrast, mutants had greater amounts of ABC transporters needed to balance cellular osmolarity. Hence, the pleiotropic effects of OpgGH reach across the proteome and the data are consistent with the mutant phenotypes. A model that explains reduced virulence is proposed.