目的　研究伤寒杆菌耐药质粒pRST98能否介导细菌毒力。方法　将pRST98导入鼠伤寒杆菌低毒株RIA ,经口和腹腔感染小鼠 ,测定半数致死量 (LD50 ) ;口饲细菌后检测在体内播散、繁殖及引起脏器的组织学改变 ;在体外对其进行细胞的粘附和侵袭试验。分别用含pRST98的野生伤寒杆菌、消除pRST98的突变体菌株及pRST98再重新导入突变体的菌株 ,研究对人、兔及豚鼠血清杀菌的抵抗力。结果　导入pRST98的鼠伤寒杆菌口服和腹腔注射组LD50 比阴性对照分别降低约 70 0倍和75倍 ;在小鼠肠系膜淋巴结、脾和肝脏内增殖 (P <0 .0 5 )并引起脏器严重病变 ;但在体外不影响鼠伤寒杆菌对HEp 2、CHO和HeLa细胞的粘附和侵袭。携带pRST98的伤寒杆菌在血清中的抵抗力显著高于无此质粒的菌株 (P <0 .0 5 )。结论　伤寒杆菌耐药质粒pRST98不但介导对药物的抗性 ,同时还能使宿主菌的毒力增强。 Objective To investigate whether Salmonella typhi resistance plasmid pRST98 can mediate bacterial virulence. Methods The pRST98 was introduced into RIA with low Salmonella typhimurium strain. The mice were inoculated intraperitoneally and intraperitoneally to determine the lethal dose (LD50). After oral administration, the bacteria were disseminated and propagated in organism and caused histological changes in organs. The cells were subjected to adhesion and invasion tests. Resist strains of pRST98, pRST98 and pRST98 were respectively reintroduced into the mutant strains to study the bactericidal effect on the bacteria in humans, rabbits and guinea pigs. Results The LD50 of oral and intraperitoneal injection of Salmonella typhimurium into pRST98 was reduced by about 70 times and 75 times respectively than that of the negative control. Proliferation of mouse mesenteric lymph nodes, spleen and liver (P <0.05) But did not affect the adhesion and invasion of S. typhimurium to HEp 2, CHO and HeLa cells in vitro. Salmonella typhimurium harboring pRST98 had significantly higher serum resistance than the isolates without this plasmid (P <0.05). Conclusion Salmonella typhi resistance plasmid pRST98 not only mediates drug resistance, but also enhances virulence of host bacteria.