Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development

Abstract

Francisella tularensis is a facultative intracellular gram-negative pathogen and the etiological agent of the zoonotic disease tularemia. Recent advances in the field of Francisella genetics have led to a rapid increase in both the generation and subsequent characterization of mutant strains exhibiting altered growth and/or virulence characteristics within various model systems of infection. In this review, we summarize the major properties of several Francisella species, including F. tularensis and F. novicida, and provide an up-to-date synopsis of the genes necessary for pathogenesis by these organisms and the determinants that are currently being targeted for vaccine development.

FIG. 1.

Illustration of Francisella survival inside macrophages. Francisella is taken up by macrophages through looping phagocytosis (33) into an endosomal compartment that transiently acquires late endosome-associated markers (29, 32). Francisella then exits the phagosomal compartment and replicates to high numbers in the cellular cytosol. Prior to lysis of the cell, Francisella has been shown to reside in an autophagy-like compartment (27).