Nasal immunization with attenuated Salmonella Typhimurium expressing an MrpA-TetC fusion protein significantly reduces Proteus mirabilis colonization in the mouse urinary tract

J Med Microbiol. 2011 Jul;60(Pt 7):899-904. doi: 10.1099/jmm.0.030460-0. Epub 2011 Mar 17.

Abstract

The development of effective strategies to prevent urinary tract infections (UTIs) has become an important goal in public health. Proteus mirabilis is commonly associated with complicated UTIs and expresses several virulence factors, including mannose-resistant Proteus-like (MR/P) fimbriae. Here, a fusion protein formed from MrpA, the structural protein of MR/P fimbriae, and TetC, a non-toxic but highly immunogenic fragment of tetanus toxin, to be delivered by an attenuated Salmonella Typhimurium mutant in vivo was constructed. The ability of this strain to induce an immune response and to protect mice against a urinary tract challenge with P. mirabilis was investigated. The protein was successfully expressed in S. Typhimurium. After two immunization doses, intra-nasally vaccinated mice showed a significant increase in specific serum IgG against MrpA and against Salmonella lipopolysaccharide, as well as a significant decrease in kidney and bladder colonization by P. mirabilis after challenge. However, no significant correlation was observed between antibody response and kidney or bladder colonization. MrpA fused to TetC and expressed in S. Typhimurium effectively protected mice against an experimental P. mirabilis UTI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology
  • Female
  • Gene Expression Regulation, Bacterial / physiology
  • Humans
  • Immunoglobulin G / blood
  • Mice
  • Mice, Inbred BALB C
  • Proteus Infections / microbiology
  • Proteus Infections / prevention & control*
  • Proteus mirabilis / immunology*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism*
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / immunology
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / prevention & control*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • TetC protein, Bacteria
  • Vaccines, Attenuated
  • mrpA protein, Proteus mirabilis