Identification of an outer membrane protein of Salmonella enterica serovar Typhimurium as a potential vaccine candidate for Salmonellosis in mice

Microbes Infect. 2013 May;15(5):388-98. doi: 10.1016/j.micinf.2013.02.005. Epub 2013 Feb 26.

Abstract

We report our investigation of the functions of PagN in Salmonella pathogenesis and its potential as a vaccine candidate. Further investigation conducted in this study indicates that the outer membrane protein PagN is important for Salmonella adhesion/invasion of epithelial cells as well as bacterial virulence. When pagN was deleted from Salmonella enterica serovar Typhimurium (S. Typhimurium), the adhesion and invasion of HT-29 epithelial cells was significantly decreased compared with the wild type strain. Mice infected with the pagN mutant strain exhibited less pathological signs in the intestine and survived longer than the wild-type-infected mice. PagN is widely distributed and conserved among clinical isolates of different Salmonella serovars, making PagN a potential vaccine candidate for Salmonella infection. To elucidate the potential of PagN as a vaccine, we expressed and purified recombinant PagN (rPagN). When rPagN was tested in mice, it provided significant protection against Salmonella infection in vivo. In vitro, anti-PagN serum enhanced clearance of Salmonella, indicating a contribution of PagN-specific antibodies to the killing process. This correlates well with the observed protection of mice immunized with rPagN. Our preliminary results indicate more functions of PagN in S. Typhimurium virulence as well as its potential as a protective vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology*
  • Animals
  • Bacterial Adhesion
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Cell Line
  • Disease Models, Animal
  • Epithelial Cells / microbiology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Salmonella Infections, Animal / immunology
  • Salmonella Infections, Animal / mortality
  • Salmonella Infections, Animal / pathology
  • Salmonella Infections, Animal / prevention & control*
  • Salmonella Vaccines / administration & dosage
  • Salmonella Vaccines / genetics
  • Salmonella Vaccines / immunology*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / physiology
  • Survival Analysis
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adhesins, Bacterial
  • Bacterial Outer Membrane Proteins
  • Salmonella Vaccines
  • Vaccines, Subunit
  • Vaccines, Synthetic