Salmonella enterica serovar Typhi uses two type 3 secretion systems to replicate in human macrophages and to colonize humanized mice.

serovar Typhi is a human-restricted pathogen that causes typhoid fever. Understanding the key virulence mechanisms that facilitate Typhi replication in human phagocytes will enable rational vaccine and antibiotic development to limit spread of this pathogen. While Typhimurium replication in murine models has been studied extensively, there is limited information available about Typhi replication in human macrophages, some of which directly conflicts with findings from Typhimurium murine models. This study establishes that both of Typhi's two Type 3 Secretion Systems (T3SS-1 and -2) contribute to intramacrophage replication and virulence.