Palmitoylation state impacts induction of innate and acquired immunity by the Salmonella enterica serovar typhimurium msbB mutant

Infect Immun. 2011 Dec;79(12):5027-38. doi: 10.1128/IAI.05524-11. Epub 2011 Sep 19.


Lipopolysaccharide (LPS), composed of lipid A, core, and O-antigen, is a major virulence factor of Salmonella enterica serovar Typhimurium, with lipid A being a major stimulator to induce the proinflammatory response via the Toll-like receptor 4 (TLR4)-MD2-CD14 pathway. While Salmonella msbB mutants lacking the myristate chain in lipid A were investigated widely as an anticancer vaccine, inclusion of the msbB mutation in a Salmonella vaccine to deliver heterologous antigens has not yet been investigated. We introduced the msbB mutation alone or in combination with mutations in other lipid A acyl chain modification genes encoding PagL, PagP, and LpxR into wild-type S. enterica serovar Typhimurium. The msbB mutation reduced virulence, while the pagL, pagP, and lpxR mutations did not affect virulence in the msbB mutant background when administered orally to BALB/c mice. Also, all mutants exhibited sensitivity to polymyxin B but did not display sensitivity to deoxycholate. LPS derived from msbB mutants induced less inflammatory responses in human Mono Mac 6 and murine macrophage RAW264.7 cells in vitro. However, an msbB mutant did not decrease the induction of inflammatory responses in mice compared to the levels induced by the wild-type strain, whereas an msbB pagP mutant induced less inflammatory responses in vivo. The mutations were moved to an attenuated Salmonella vaccine strain to evaluate their effects on immunogenicity. Lipid A modification caused by the msbB mutation alone and in combination with pagL, pagP, and lpxR mutations led to higher IgA production in the vaginal tract but still retained the same IgG titer level in serum to PspA, a test antigen from Streptococcus pneumoniae, and to outer membrane proteins (OMPs) from Salmonella.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Cell Line
  • Humans
  • Immunity, Innate
  • Lipoylation
  • Mice
  • Mutation
  • Salmonella Infections, Animal / prevention & control*
  • Salmonella Vaccines / immunology*
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / pathogenicity
  • Virulence


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Salmonella Vaccines