Francisella tularensis: taxonomy, genetics, and Immunopathogenesis of a potential agent of biowarfare

Abstract

Tularemia is a zoonosis of humans caused by infection with the facultative intracellular bacterium Francisella tularensis. Interest in F. tularensis has increased markedly in the past few years because of its potential use as an agent of bioterrorism. Five subspecies of this organism are found in the Northern hemisphere, but only F. tularensis subsp. tularensis and subsp. holarctica cause disease in humans. This review summarizes what is known about the pathogenesis of tularemia with a focus on bacterial surface components such as lipopolysaccharide and capsule as well as information obtained from the F. tularensis subsp. tularensis SCHU S4 genome. In particular, the mechanisms of action of recently identified virulence factors are discussed in the context of bacterial replication in macrophages and manipulation of the host inflammatory response. Throughout this report, shared and unique features of F. tularensis subsp. tularensis, subsp. holarctica, and subsp. novicida are discussed.

Figure 1

Evolutionary schema based on loss of regions of difference and extensive nucleotide variation. Adapted from Svennson et al. (113).

Figure 2

The lipid A of F. tularensis subsp. holarctica strain 1547. Note the asymmetrical lipid A structure and the absence of O-acylation on hexosamine II (arrow). The phosphogalactosamine substitution on the 4′-position of this hexosamine is also unique to Francisella.

Figure 3

A whole mount electron micrograph of F. tularensis subsp. holarctica strain 1547 fixed in glutaraldehyde with ruthenium red and stained with monoclonal antibody XE8 and secondary antibodies conjugated to colloidal gold to show the putative surface capsule. Magnification: ×15,000.