The type VI secretion system gene cluster of Salmonella typhimurium: required for full virulence in mice

Type VI secretion system (T6SS) has increasingly been believed to participate in the infection process for many bacterial pathogens, but its role in the virulence of Salmonella typhimurium remains unclear. To look into this, we deleted the T6SS cluster from the genome of S. typhimurium 14028s and analyzed the phenotype of the resulting T6SS knockout mutant (T6SSKO mutant) in vitro and in vivo. We found that the T6SSKO mutant exhibited reduced capability in colonizing the spleen and liver in an in vivo colonization competition model in BALB/c mice infected by the oral route. Additionally, infection via intraperitoneal administration also showed that the T6SSKO mutant was less capable of colonizing the mouse spleen and liver than the wild-type strain. We did not detect significant differences between the T6SSKO and wild-type strains in epithelial cell invasion tests. However, in the macrophage RAW264.7 cell line, the T6SSKO mutant survived and proliferated significantly more poorly than the wild-type strain. These findings indicate that T6SS gene cluster is required for full virulence of S. typhimurium 14028s in BALB/c mice, possibly due to its roles in bacterial survival and proliferation in macrophages.