Characterization of the Burkholderia mallei tonB mutant and its potential as a backbone strain for vaccine development

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 hypersecretion 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 104 cfu of tmm001. at 21 days post-immunization,tmm001-treated animals showed significantly higher levels of b. malleispecific 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. © 2015 mott et al.