AI Article Synopsis
- Francisella tularensis is a highly virulent bacterium that causes tularemia and is a priority for creating vaccines, with specific attention on two types: type A (Ft tularensis) and type B (Ft holarctica).
- Researchers focused on six specific genes from less virulent strains to create mutant versions of the lethal type A strain, finding that certain mutants (gua mutants) were unable to replicate in mouse immune cells and showed reduced virulence in live subjects.
- However, while these mutants demonstrated some protective ability in rabbits, they failed to adequately protect mice from lethal doses of the wild-type strain, indicating variability in vaccine effectiveness across different strains and animal models, which is crucial for future vaccine development efforts.
Article Abstract
Francisella tularensis (Ft), the etiological agent of tularemia and a Tier 1 select agent, has been previously weaponized and remains a high priority for vaccine development. Ft tularensis (type A) and Ft holarctica (type B) cause most human disease. We selected six attenuating genes from the live vaccine strain (LVS; type B), F. novicida and other intracellular bacteria: FTT0507, FTT0584, FTT0742, FTT1019c (guaA), FTT1043 (mip) and FTT1317c (guaB) and created unmarked deletion mutants of each in the highly human virulent Ft strain Schu S4 (Type A) background. FTT0507, FTT0584, FTT0742 and FTT1043 Schu S4 mutants were not attenuated for virulence in vitro or in vivo. In contrast, Schu S4 gua mutants were unable to replicate in murine macrophages and were attenuated in vivo, with an i.n. LD50 > 10(5) CFU in C57BL/6 mice. However, the gua mutants failed to protect mice against lethal challenge with WT Schu S4, despite demonstrating partial protection in rabbits in a previous study. These results contrast with the highly protective capacity of LVS gua mutants against a lethal LVS challenge in mice, and underscore differences between these strains and the animal models in which they are evaluated, and therefore have important implications for vaccine development.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462183 | PMC |
| http://dx.doi.org/10.1093/femspd/ftv036 | DOI Listing |
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