Salmonella enterica subsp. Typhimurium ΔsifA mutants escape to the host cytosol and replicate in epithelial cells but are killed upon entry into the macrophage cytosol, suggesting the presence of both cell type-specific cell autonomous defenses (CADs) and bacterial survival mechanisms (3). We next asked whether the cytosolic survival defects of our mutants were macrophage specific. Using the plasmid-based bacteriolysis assay, we assessed survival of each of our mutants in epithelial (Caco-2) cells and fibroblasts (BHKs) (Fig. S3A and B). Only the yvcJ::Tn mutant was significantly impaired for survival in all cell types, suggesting that YvcJ is generally required for cytosolic survival. nrdD::Tn, pdhC::Tn, menD::Tn, and menF::Tn mutants were significantly impaired for survival in macrophages and Caco-2 cells but not BHKs. Surprisingly, given the in vitro and macrophage bacteriolysis phenotypes, lmo1602::Tn mutants were not impaired for survival in either Caco-2 cells or BHKs. These observations of cell type-specific bacteriolysis are consistent with the idea of specific CADs and/or nutritional immunity in the cytosol of different cell types.