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.

Development of novel plasmid vectors and a promoter trap system in Francisella tularensis compatible with the pFLN10 based plasmids

“…The sequencing of the inserts did not reveal any consensus sequence to be utilized as an intracellular activated promoter and the majority of the promoters examined are upstream of hypothetical proteins or proteins that contain little or no functional annotation. This confirms what little, we know of the virulence and regulation within F. tularensis (McLendon et al, 2006;Oyston et al, 2004;. Further larger studies identifying more promoters will be required to delineate an intracellular activated promoter consensus sequence and we plan on extending these studies to establish a regulatory network within F. tularensis.…”

Large Scale Structural Rearrangement of a Serine Hydrolase from Francisella tularensis Facilitates Catalysis

“…The amino acid numbering corresponds to the amino acid numbering in FTT258. The number in parentheses refers to whether the protein has been designated as a closer homologue of human APT1 (1) or APT2 (2 …”

“…Francisella tularensis is an endemic, zoonotic Gram-negative bacterium and the causative agent for the febrile disease, tularemia (1,2). Although F. tularensis infection is uncommon in the general population, the extreme virulence and relatively high mortality rate of F. tularensis infection have led to the classification of F. tularensis as a probable biological warfare agent (3,4).…”

Pivotal role of the Francisella tularensis heat-shock sigma factor RpoH

“…Human infections can occur after ingestion of contaminated water or food, through arthropod bites, from contaminated animal carcasses, or by inhalation of bacteria. Due to its high infectivity and the severity of disease, F. tularensis has been classified by the US Centers for Disease Control as a potential biological weapon (for reviews, see McLendon et al, 2006;Sjostedt, 2006). The pathogenicity of F. tularensis is largely dependent on its ability to replicate inside host cells, and in particular in macrophages in vivo.…”