Francisella virulence: significant advances, ongoing challenges and unmet needs.

Francisella tularensis, the causative agent of tularemia, is an organism of concern as a potential biowarfare agent. Progress towards understanding the molecular basis of pathogenicity has been hampered by a lack of tools with which to manipulate the pathogen. However, the availability of genome sequence data for a range of strains and the development of a range of plasmids and mutagenesis protocols for use in Francisella has resulted in a huge advance in understanding. No licensed vaccine is yet available. Various approaches towards a new vaccine are being evaluated, but novel adjuvants and delivery systems are needed to induce the complex response required for immunity. Better animal models to more accurately represent human responses to infection are also required.