Abstract

Plasmid pR_ST98 is a hybrid antibiotic resistance-virulence plasmid isolated fromSalmonella 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 Human-derived 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.

Key words: Salmonella enterica serovar Typhi, plasmid pR_ST98, macrophage, apoptosis, nitric oxide, caspase-3 activity.