How intracellular bacteria survive: Surface modifications that promote resistance to host innate immune responses

Bacterial pathogens regulate the expression of virulence factors in respons e to environmental signals. In the case of salmonellae, many virulence fact ors are regulated via PhoP/PhoQ, a two-component signal transduction system that is repressed by magnesium and calcium in vitro. PhoP/PhoQ-activated g enes promote intracellular survival within macrophages, whereas PhoP-repres sed genes promote entrance into epithelial cells and macrophages by macropi nocytosis and stimulate epithelial cell cytokine production. PhoP-activated genes include those that alter the cell envelope through structural altera tions of lipopolysaccharide and lipid A, the bioactive component of lipopol ysaccharide. PhoP-activated changes in the bacterial envelope likely promot e intracellular survival by increasing resistance to host cationic antimicr obial peptides and decreasing host cell cytokine production.