Effect of a purA mutation on efficacy of Salmonella live-vaccine vectors

Abstract

We made delta aroA, delta purA, and delta aroA delta purA derivatives of a strain of Salmonella dublin and isolated a nalidixate-resistant mutant of each construct. An inoculum of each of the nearly isogenic nalidixate-resistant auxotrophs was administered to BALB/c mice by gavage. The ability of each strain to colonize, invade, persist in tissues, and evoke serum and mucosal antibody responses to the lipopolysaccharide of the parent strain was examined. Only the delta aroA strain colonized, invaded, persisted, and (more importantly) evoked sustained significant serum and mucosal antibody responses. Neither the delta purA nor the delta aroA delta purA strain showed any of these abilities. These observations demonstrate that the purA defect, which causes a requirement for adenine, reduces the live-vaccine efficacy of attenuated Salmonella strains and may limit the effectiveness of Salmonella strains as carriers of heterologous antigens. These findings may be important in the selection of attenuated S. typhi strains for use in humans either as antityphoid live vaccines or as vectors for antigens of other pathogens.