title: Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.
abstract: BACKGROUND
  In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis.
  
  
  RESULTS
  Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4) CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001.
  
  
  CONCLUSIONS
  Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Mott
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Sudhamathi
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Sbrana
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Endsley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Torres
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001428:Bacterial Vaccines / Q000235:genetics*; D042726:Burkholderia mallei / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D055808:Drug Discovery / Q000379:methods; D005260:Female; D005896:Glanders / Q000517:prevention & control*; D007501:Iron / Q000378:metabolism; D008554:Melioidosis / Q000517:prevention & control*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D016019:Survival Analysis
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D017931:DNA Primers; D008565:Membrane Proteins; C057616:tonB protein, Bacteria; D007501:Iron