| Abstrakt: |
ABSTRACTInfection with Salmonellaspp. is a significant source of disease globally. A substantial proportion of these infections are caused by Salmonella entericaserovar Typhimurium. Here, we characterize the role of the enterobacterial common antigen (ECA), a surface glycolipid ubiquitous among enteric bacteria, in S.Typhimurium pathogenesis. Construction of a defined mutation in the UDP-N-acetylglucosamine-1-phosphate transferase gene, wecA, in two clinically relevant strains of S.Typhimurium, TML and SL1344, resulted in strains that were unable to produce ECA. Loss of ECA did not affect the gross cell surface ultrastructure, production of lipopolysaccharide (LPS), flagella, or motility. However, the wecAmutant strains were attenuated in both oral and intraperitoneal mouse models of infection (P< 0.001 for both routes of infection; log rank test), and virulence could be restored by complementation of the wecAgene in trans. Despite the avirulence of the ECA-deficient strains, the wecAmutant strains were able to persistently colonize systemic sites (spleen and liver) at moderate levels for up to 70 days postinfection. Moreover, immunization with the wecAmutant strains provided protection against a subsequent lethal oral or intraperitoneal challenge with wild-type S.Typhimurium. Thus, wecAmutant (ECA-negative) strains of Salmonellamay be useful as live attenuated vaccine strains or as vehicles for heterologous antigen expression. |
