The Salmonella virulence plasmid spv genes are required for cytopathology in human monocyte-derived macrophages

The pathogenesis of serious systemic Salmonella infections is characterized by survival and proliferation of bacteria inside macrophages. Infection of human monocyte-derived macrophages in vitro with S. typhimurium or S. dubl in produces cytopathology characterized by detachment of cells that contain large numbers of proliferating bacteria. This cytopathology is dependent o n the expression of the bacterial spv genes, a virulence locus previously s hown to markedly enhance the ability of Salmonella to produce systemic dise ase. After 24 h of infection, macrophage cultures contain two populations o f bacteria: (i) proliferating organisms present in a detached cell fraction ; and (ii) a static bacterial population in macrophages remaining attached to the culture well. Mutations in either the essential transcriptional acti vator SpvR or the key SpvB protein markedly reduce the cytopathic effect of Salmonella infection. The spv-dependent cytopathology in macrophages exhib its characteristics of apoptosis, with release of nucleosomes into the cyto plasm, nuclear condensation and DNA fragmentation. The current findings sug gest that the mechanism of the spv effect is through induction of increased cytopathology in host macrophages.