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PLoS Negl Trop Dis. 2015 Jun 26;9(6):e0003863. doi: 10.1371/journal.pntd.0003863. eCollection 2015.

Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

Author information

1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
2
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.
3
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.
4
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.

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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.

PMID:
26114445
PMCID:
PMC4482651
DOI:
10.1371/journal.pntd.0003863
[Indexed for MEDLINE]
Free PMC Article

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