Pathogenicity and virulence of Francisella tularensis

Figures & data

Table 1. Reservoir, vectors and pathogenicity for humans of different species of Francisella..

Species or subspecies of Francisella	Reservoir/vectors	Pathogenic for humans	References
F. tularensis subsp tularensis	More than 250 animal species, including lagomorphs and small rodents Ixodidae ticks, mosquitoes and deer flies Contaminated environment (soil, water.)	yes	[25]
F. tularensis subsp holarctica	More than 250 animal species, including lagomorphs and small rodents Ixodidae ticks, mosquitoes and deer flies Contaminated environment (soil, water.)	yes
F. tularensis subsp mediasiatica	Ticks	No	[28]
F. novicida	Sea- water brackish-water	Occasionally (immunocompromised patients, neardrowning accident)
F. hispaniensis	Poorly characterized Aquatic sources … .	Rarely
F. persica	Ticks	No	[26]
F. opportunistica	environment	Rarely immunocompromised patients	[27]
F. philomiragia	salt- or brackish-water sick muskrat Dermacentor ticks	Occasionally (near-drowning accident, immunocompromised patients -especially people suffering from chronic granulomatous disease)
F. noatunensis F. noatunensis subsp. orientalis F. noatunensis subsp. noatunensis	warm- and cold-water fish pathogens	No	[29]
F. salimarina/F. marina/F. salina	Sea-water Fish pathogens	Very rarely (one case described)	[29]
F. endocilophora	endosymbionts of marine ciliates	No	[29]
F. halioticida	Pathogen for molluscs	Very rarely (one case described)	[30]
F. uliginis	sea-water	No	[29]

Table 2. Characteristics of Francisella subspecies traditionally used to study virulence.

	F. novicida	F. tularensis subsp tularensis	F. tularensis subsp holarctica	References
Reference strains	U112	SCHU S4	LVS
Genome size	1,910,031 bp	1,892,819 bp	1,895,998 bp	[33]
Protein coding genes	1731	1145	1380	[33]
Sequence identity to SCHU S4	98.1%	/	99.2%	[34]
FPI	1 copy	2 copies	2 copies	[35]
Type VI secretion system effectors	OpiA, OpiB1–3, pdpD, pdpC	Splitted OpiA in 2 ORF, small OpiB*, pdpD, pdpC	Splitted OpiA in 2 ORF, small OpiB**, pdpC	[35–37]

*Ankyrin repeat region is absent.

**Ankyrin repeats region absent and deletion in the C-ter region.

Figure 1. Francisella life cycle and the main host and bacterial factors involved at each step.

(a) Schematic representation of Francisella life cycle in macrophages. Merocytophagy of uninfected macrophages (red) is shown in panel 5. (b) For each step in the life cycle, the main host and bacterial factors (in italics) are shown.

Figure 2. Francisella pathogenicity island, its transcriptomic regulation and its encoded T6SS.

(a) Transcriptomic regulation of FPI gene transcription (see text for details). (b) Structure of F. novicida FPI. The main differences with SCHU S4 and LVS FPI are shown. The genes encoding structural components are in colour (see C), the genes encoding effectors are in grey and the genes encoding proteins are unknown functions in white. (c) Structural model of Francisella T6SS with Francisella protein name on the left and the name of their T6SSⁱ homologues on the right.

Figure 3. Overview of the innate immune responses upon macrophage infection.

Francisella escapes TLR4 recognition and is recognized by TLR2, which leads to NF-κB activation. Early detection of nucleic acids by cGAS leads to the production of the second messenger cGAMP for STING activation, resulting in IRF3 activation. IFN-β or IFN-γ induces guanylate binding protein (GBPs) production in an IRF1-dependent manner. GBPs cover Francisella and promote Caspase-4 recognition of Francisella LPS in human macrophages, DNA release into the host cytosol, and activation of the Aim2 inflammasome in murine macrophages culminating in GasderminD (GSDMD) cleavage, pore formation, cytokine secretion, and pyroptosis. T.F.: transcription factors.

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Data Availability statement

The data, materials and original svg figures that support the results or analyses presented in this paper are freely available upon request.