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Francisella


General information:
Nonmotile, encapsulated, Gram negative coccobacilli
The genus consists of three recognized species: Francisella tularensis, Francisella novicida, and Francisella philomiragia
F. tularensis consists of several subspecies that vary in virulence potential. F. tularensis ssp. tularensis, which is also referred to as Type A, is found mostly in North America and causes the most severe form of the disease. F. tularensis ssp. holarctica, which is also referred to as Type B, is found mostly in northern Europe and causes a milder form of the disease.
Characteristics:
Zoonotic facultative intracellular pathogen
A typical cytosol-dwelling pathogen: Francisella survival and proliferation strategies rely on physical escape from its original phagosome and replication in the host-cell cytosol
A "stealth" pathogen: first evades host immune detection, but subsequently induces a cytokine storm that causes host death
Disease:
F. tularensis is highly infectious and causes a potentially debilitating febrile illness known as tularemia, listed as a category A potential bioterrorism agent
F. novicida and F. philomiragia are rarely pathogenic in man and usually only in individuals who are severely immunocompromised
Genomes (comparative pathogenomics):
F. cf. novicida Fx1, 1913619 bp, NC_017450
F. cf. tularensis subsp. novicida 3523, 1945310 bp, NC_017449
F. noatunensis subsp. orientalis str. Toba 04, 1847202 bp, NC_017909
F. novicida U112, 1910031 bp, NC_008601
F. philomiragia subsp. philomiragia ATCC 25017, 2045775 bp, NC_010336
F. sp. TX077308, 2035931 bp, NC_015696
F. tularensis subsp. holarctica F92, 1886888 bp, NC_019537
F. tularensis subsp. holarctica FSC200, 1894157 bp, NC_019551
F. tularensis subsp. holarctica FTNF002-00, 1890909 bp, NC_009749
F. tularensis subsp. holarctica LVS, 1895994 bp, NC_007880
F. tularensis subsp. holarctica OSU18, 1895727 bp, NC_008369
F. tularensis subsp. mediasiatica FSC147, 1893886 bp, NC_010677
F. tularensis subsp. tularensis FSC198, 1892616 bp, NC_008245
F. tularensis subsp. tularensis NE061598, 1892681 bp, NC_017453
F. tularensis subsp. tularensis SCHU S4, 1892775 bp, NC_006570
F. tularensis subsp. tularensis TI0902, 1892744 bp, NC_016937
F. tularensis subsp. tularensis TIGB03, 1968651 bp, NC_016933
F. tularensis subsp. tularensis WY96-3418, 1898476 bp, NC_009257
Publications:
Rohmer L, et al., 2007. Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains. Genome Biol 8(6):R102.
Svensson K, et al., 2012. Genome sequence of Francisella tularensis subspecies holarctica strain FSC200, isolated from a child with tularemia. J Bacteriol 194(24):6965-6966.
Barabote RD, et al., 2009. Complete genome sequence of Francisella tularensis subspecies holarctica FTNF002-00. PLoS One 4(9):e7041.
Petrosino JF, et al., 2006. Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence. J Bacteriol 188(19):6977-6985.
Larsson P, et al., 2009. Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen. PLoS Pathog 5(6):e1000472.
Chaudhuri RR, et al., 2007. Genome sequencing shows that European isolates of Francisella tularensis subspecies tularensis are almost identical to US laboratory strain Schu S4. PLoS One 2(4):e352.
Nalbantoglu U, et al., 2010. Large direct repeats flank genomic rearrangements between a new clinical isolate of Francisella tularensis subsp. tularensis A1 and Schu S4. PLoS One 5(2):e9007.
Larsson P, et al., 2005. The complete genome sequence of Francisella tularensis, the causative agent of tularemia. Nat Genet 37(2):153-159.
Modise T, et al., 2012. Genomic comparison between a virulent type A1 strain of Francisella tularensis and its attenuated O-antigen mutant. J Bacteriol 194(10):2775-2776.
Beckstrom-Sternberg SM, et al., 2007. Complete genomic characterization of a pathogenic A.II strain of Francisella tularensis subspecies tularensis. PLoS One 2(9):e947.
Figures:
Model of the Francisella intracellular cycle. (From: Celli J, Zahrt TC, 2013. Mechanisms of Francisella tularensis intracellular pathogenesis. Cold Spring Harb Perspect Med 3(4):a010314.)

Major virulence factors in Francisella:
Adherence
EF-Tu
FsaP
Type IV pili
Immune evasion
Capsule
LPS
Intracellular survival
Acid phosphatase
DipA
OmpA
RipA
Iron uptake
FupA
Rhizoferrin
Magnesium uptake
FmvB
Metabolic adaptation
AnsP
ArgP
Biotin synthesis
GGT
GadC
IleP
Purine biosynthesis
Pyrimidine biosynthesis
Secretion system
T6SS
Pathogenicity islands in Francisella:
FPI
Location of virulence-associated genes in F. tularensis:
View the legend


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