Salmonella enterica serovar Typhi plasmid pRST98 enhances caspase-3 mediated macrophage apoptosis by suppressing nitric oxide production

Abstract

Plasmid pR ST98 is a hybrid antibiotic resistance-virulence plasmid isolated from Salmonella enterica serovar typhi (S. typhi). Previously, we transferred pR ST98 into attenuated Salmonella enterica serovar typhimurium (S. typhimurium) strain RIA to create a transconjugant pR ST98 /RIA and indicated that pR ST98 could enhance apoptosis of infected murine macrophages J774A.1. However, S. typhimurium-mice interaction cannot reflect all characteristics of S. typhi-human interaction. The present study Humanderived macrophage-like cell line THP-1 was infected with wild-type (ST8), pR ST98 -deletion (ST8-ΔpR ST98 ) and complemented (ST8-c-pR ST98 ) S. typhi strains to gain more precise and further insight into the role of pR ST98 in interaction between S. typhi and human macrophage. Macrophage apoptosis, caspase-3 activity and nitric oxide (NO) production were assayed. The results demonstrated that macrophages infected with ST8 and ST8-c-pR ST98 displayed more extensive apoptosis than those infected with ST8-ΔpR ST98 . Further studies showed that pR ST98 could increase caspase-3 activity and suppress NO production. Pretreated macrophages with NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) enhanced S. Typhi-induced macrophage apoptosis. The research data indicate that the plasmid pR ST98 can enhance caspase-3 mediated macrophage apoptosis by suppressing NO production.