RESUMEN
BACKGROUND: Salmonella paratyphi C is one of the few human-adapted pathogens along with S. typhi, S. paratyphi A and S. paratyphi B that cause typhoid, but it is not clear whether these bacteria cause the disease by the same or different pathogenic mechanisms. Notably, these typhoid agents have distinct sets of large genomic insertions, which may encode different pathogenicity factors. Previously we identified a novel prophage, SPC-P1, in S. paratyphi C RKS4594 and wondered whether it might be involved in pathogenicity of the bacteria. RESULTS: We analyzed the sequence of SPC-P1 and found that it is an inducible phage with an overall G+C content of 47.24%, similar to that of most Salmonella phages such as P22 and ST64T but significantly lower than the 52.16% average of the RKS4594 chromosome. Electron microscopy showed short-tailed phage particles very similar to the lambdoid phage CUS-3. To evaluate its roles in pathogenicity, we lysogenized S. paratyphi C strain CN13/87, which did not have this prophage, and infected mice with the lysogenized CN13/87. Compared to the phage-free wild type CN13/87, the lysogenized CN13/87 exhibited significantly increased virulence and caused multi-organ damages in mice at considerably lower infection doses. CONCLUSIONS: SPC-P1 contributes pathogenicity to S. paratyphi C in animal infection models, so it is possible that this prophage is involved in typhoid pathogenesis in humans. Genetic and functional analyses of SPC-P1 may facilitate the study of pathogenic evolution of the extant typhoid agents, providing particular help in elucidating the pathogenic determinants of the typhoid agents.
Asunto(s)
Bacteriófago P1/genética , Profagos/genética , Salmonella paratyphi C/patogenicidad , Salmonella paratyphi C/virología , Animales , Bacteriófago P1/ultraestructura , Recuento de Colonia Microbiana , ADN Viral/genética , Genoma Bacteriano/genética , Humanos , Lisogenia/genética , Ratones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Fiebre Paratifoidea/genética , Fiebre Paratifoidea/microbiología , Fiebre Paratifoidea/patología , Filogenia , Reacción en Cadena de la Polimerasa , Profagos/ultraestructura , Salmonella paratyphi C/clasificación , Salmonella paratyphi C/crecimiento & desarrollo , Serotipificación , Activación Viral/genéticaRESUMEN
The Vi capsular polysaccharide (Vi) is both a virulence factor and a protective antigen of Salmonella typhi; its pathogenic role for Salmonella paratyphi C is less well understood. We found no differences between the antigenic and immunogenic properties and the structure of the Vi from representative strains of S. paratyphi C, S. typhi, and Citrobacter freundii. There were, however, differences in both the amount produced per cell and the degree of association with the cell among the Vi from the three species of Enterobacteriaceae. S. paratyphi C produced less Vi than both the wild-type S. typhi and C. freundii did, and it showed the fastest release of Vi into the media. These findings may provide an explanation for the inability of the Vi to inhibit completely the agglutination of S. paratyphi C by anti-O sera. In an outbreak of enteric fever caused by S. paratyphi C, 66 of 78 isolates (85%) were Vi positive.
Asunto(s)
Antígenos Bacterianos/análisis , Polisacáridos Bacterianos/análisis , Salmonella paratyphi C/inmunología , Salmonella/inmunología , Adolescente , Adulto , Agar , Animales , Anticuerpos Antibacterianos/biosíntesis , Antígenos Bacterianos/inmunología , Niño , Preescolar , Citrobacter/metabolismo , Humanos , Sueros Inmunes , Inmunodifusión , Lactante , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fiebre Paratifoidea/microbiología , Polisacáridos Bacterianos/biosíntesis , Polisacáridos Bacterianos/inmunología , Conejos , Salmonella paratyphi C/crecimiento & desarrollo , Salmonella paratyphi C/metabolismo , Salmonella typhi/metabolismoRESUMEN
The in vivo growth of Salmonella paratyphi A, S. paratyphi B, S. paratyphi C, and S. typhi, as well as of an S. typhi-typhimurium hybrid, was studied in three different strains of mice. S. paratyphi A and B and S. typhi demonstrated very little growth potential in any of the intravenously infected mice, even after as many as 20 serial mouse passages. It was noted, however, that small numbers of viable S. paratyphi B and S. typhi persisted in the spleens of infected mice for up to 28 days. Salmonella paratyphi C and the S. typhi-typhimurium hybrid gave rise to progressive systemic infections beginning from very small intravenous inocula. The median lethal doses for the C57B1 strain of mouse were about five organisms. The relevance of these findings with regard to the development of an animal model for studying human typhoid fever vaccines is discussed.