Evaluation of a Brucella melitensis mutant deficient in O-polysaccharide export system ATP-binding protein as a rough vaccine candidate

Microbes Infect. 2014 Aug;16(8):633-9. doi: 10.1016/j.micinf.2014.06.013. Epub 2014 Jul 18.

Abstract

Rough Brucella mutants have been sought as vaccine candidates that do not interfere with the conventional serological diagnosis of brucellosis. In this study, a rough mutant of Brucella melitensis was generated by the disruption of the wzt gene, which encodes the O-polysaccharide (O-PS) export system ATP-binding protein. In vivo, the mutant 16MΔwzt was attenuated and conferred a level of protection against B. melitensis 16M challenge similar to that conferred by the vaccine strain B. melitensis M5 in mice. In pregnant sheep, the mutant 16MΔwzt did not induce abortion. In vitro, 16MΔwzt was more susceptible to polymyxin B and complement-mediated killing than B. melitensis 16M was. Most importantly, although 16MΔwzt had a rough phenotype, it was able to synthesize O-PS and did not induce detectable specific antibodies in sheep. These results suggested that 16MΔwzt deserved to further systematic evaluation as a vaccine for target animal hosts due to its promising features.

Keywords: Brucella melitensis; O-PS export system ATP-binding protein; Rough mutant; Vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / deficiency*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins
  • Blood Bactericidal Activity
  • Brucella Vaccine / administration & dosage
  • Brucella Vaccine / genetics
  • Brucella Vaccine / immunology*
  • Brucella melitensis / genetics
  • Brucella melitensis / immunology*
  • Brucella melitensis / pathogenicity
  • Brucella melitensis / physiology
  • Brucellosis / prevention & control*
  • Disease Models, Animal
  • Female
  • Gene Deletion
  • Mice, Inbred BALB C
  • Microbial Viability / drug effects
  • O Antigens / metabolism*
  • Polymyxin B / pharmacology
  • Pregnancy
  • Sheep
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Brucella Vaccine
  • O Antigens
  • Vaccines, Attenuated
  • Wzt protein, bacteria
  • Polymyxin B