We investigate the molecular basis of environmental adaptation in bacteria that inhabit niches ranging from freshwater, to the ocean, to the interior of mammalian cells. Our studies center on the class Alphaproteobacteria, including the freshwater bacterium Caulobacter crescentus, the marine anoxygenic photosynthetic bacterium Erythrobacter litoralis, and the intracellular pathogen Brucella abortus, which is a causative agent of the zoonotic disease, brucellosis. We utilize a cross-disciplinary set of experimental and computational approaches that have defined new mechanisms of cell adhesion control, nutrient sensing, and stress sensing, and have uncovered genes and signaling pathways required for maintenance of chronic Brucella infection.