The PhoP virulence regulon and live oral Salmonella vaccines

• Published in: Vaccine Vol. 11; no. 2; pp. 122 - 125
• Main Authors: Miller, Samuel I., Loomis, Wendy P., Alpuche-Aranda, Celia, Behlau, Irmgard, Hohmann, Elizabeth
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 1993; Elsevier
• Subjects: Administration, Oral; Animals; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacteriology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; gene regulation; Genes, Bacterial; Genes, Regulator; Genetic Vectors; live oral vaccines; Membrane Proteins; Mice; Microbiology; Mutation; Operon; PhoP virulence regulon; Repressor Proteins - genetics; Salmonella; Salmonella typhi; Salmonella typhi - genetics; Salmonella typhi - immunology; Salmonella typhimurium; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Salmonella typhimurium - pathogenicity; Species Specificity; Transcription Factors - genetics; Typhoid Fever - prevention & control; Typhoid-Paratyphoid Vaccines - genetics; Typhoid-Paratyphoid Vaccines - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Virulence - genetics; Salmonella; live oral vaccines; PhoP virulence regulon; gene regulation; Pathogenesis; Vaccine strain; Virulence; Rodentia; Vaccine; Salmonella typhimurium; Vertebrata; Regulation(control); Mammalia; Gene; Mouse; Bacteria; Mutation; Attenuated strain; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/0264-410X(93)90006-J

The PhoP virulence regulon is essential to Salmonella typhimurium mouse typhoid fever pathogenesis and survival within macrophages. This virulence regulon is composed of the PhoP (transcriptional regulator) and PhoQ (environmental sensor) proteins and the genetic loci they positively (pags for PhoP activated genes) and negatively (prgs for PhoP repressed genes) regulate. Three regulated loci pagC, pagD, and prgH, when singly mutated, affect the virulence of S. typhimurium for mice. Strains with phoP locus mutations are effective as live vaccines in mice, and strains with a constitutive regulatory mutation, a point mutation in PhoQ, can protect mice against typhoid fever when only very few organisms are administered. The addition of various PhoP regulon mutations further attenuates aroA mutants of S. typhimurium, suggesting that these mutations would be useful in further attenuating vaccine strains with metabolic pathway mutations. The phoP, phoQ, pagC, and pagD genes are highly conserted between S. typhimurium and S. typhi and may be valuable as mutations in live vaccines for human typhoid fever. A plasmid suicide vector that allows deletion of the pagC gene and stable insertion of heterologous antigen genes within the deleted pagC locus has been constructed and used successfully in S. typhimurium and S. typhi.