A comprehensive study of the contribution of salmonella enterica serovar typhimurium SPI2 effectors to bacterial colonization,survivaland replication in typhoid fever, macrophage and epithelial cell infection models

Abstract

Salmonella enterica serovars are Gram-negative bacterial pathogens responsible for human diseases including gastroenteritis and typhoid fever. after ingestion, salmonella cross the intestinal epithelial barrier, where they are phagocytosed by macrophages and dendritic cells, which then enables their spread to systemic sites during cases of typhoid fever. salmonella use two type 3 secretion systems encoded by salmonella pathogenicity islands (spI) 1 and 2 to inject virulence proteins into host cells to modify cellular functions. spI1 is involved in host cell invasion and inflammation, whereas spI2 is required for intracellular survival and replication within phagocytes, and systemic spread. In this study the contribution of nearly all known spI2 effectors was examined in an in vivo model of murine typhoid fever and cell culture models of macrophage and epithelial cell infection. Unmarked, in-frame deletions of spI2 effectors were engineered in S. enterica serovar Typhimurium and the ability of the 16 different mutants to colonize and replicate was examined. In the typhoid model, we found that AspvB and AspiC mutants were attenuated for colonization of intestinal and systemic sites, while the AsseF mutant was attenuated in systemic organs. In epithelial cells, all mutants replicated to the same extent as the wild-type. In macrophages, AspiC, AsteC, AspvB, AssseK1/K2/K3, AsifA and AsifB strains replicated poorly in comparison to wild-type salmonella. This study provides a thorough screen of the majority of the known spI2 effectors evaluated under the same conditions in various models of infection, providing a foundation for comparative examination of the roles and interactions of these effectors. Salmonella enterica Typhimurium, SPI2 effectors, typhoid fever, SpvB, SseF, SpiC, gallbladder, macrophage. © 2011 Landes Bioscience.