Experimental murine tularemia caused by Francisella tularensis, live vaccine strain: a model of acquired cellular resistance

Anthony, L. S. D.; Kongshavn, Patricia A. L.

doi:10.1016/0882-4010(87)90110-0

Cited by 75 publications

(50 citation statements)

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“…LVS infections in mice are similar to human infections with fully virulent F. tularensis (39). Since survival of sublethal LVS infection leads to strong and easily measurable secondary protective immunity to LVS, we (8,15,17,46) and others (2,18,40) have found the study of this infection in mice to be an informative in vivo model of immunity to intracellular pathogens. In contrast to the properties typically associated with LPS from many pathogens, LPS purified from LVS appears to lack many of the activities usually ascribed to this molecule.…”

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confidence: 92%

Purified Lipopolysaccharide fromFrancisella tularensisLive Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon

2000

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confidence: 92%

Purified Lipopolysaccharide fromFrancisella tularensisLive Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon

2000

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“…An attenuated 'live vaccine strain' (LVS) was derived by repeated passage of subsp. holarctica in the laboratory; despite the unclear nature of the attenuating mutation(s) in this strain, it is frequently used as a laboratory model for tularaemia (Anthony & Kongshavn, 1987;Eigelsbach et al, 1951). F. tularensis subsp.…”

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confidence: 99%

Characterization of the Francisella tularensis subsp. novicida type IV pilus

et al. 2008

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Francisella tularensis causes the disease tularaemia. Type IV pili (Tfp) genes are present in the genomes of all F. tularensis subspecies. We show that the wild-type F. tularensis subsp. novicida expresses pilus fibres on its surface, and mutations in the Tfp genes pilF and pilT disrupt pilus biogenesis. Mutations in other Tfp genes (pilQ and pilG) do not eliminate pilus expression. A mutation in pilE4 eliminates pilus expression, whereas mutations in the other pilin subunits pilE1-3 and pilE5 do not, suggesting that pilE4 is the major pilus structural subunit. The virulence regulator MglA is required for pilus expression, and it regulates the transcription of a putative Tfp glycosylation gene (FTN0431). However, MglA does not regulate transcription of pilF, pilT or pilE4, and a strain lacking FTN0431 still expresses pili; thus, it is unclear how MglA regulates pilus expression. Only pilF was also required for protein secretion, while pilE4 and pilT were not, indicating that there is very little overlap of the protein secretion/Tfp functions of the pil genes. The protein secretion component pilE1 was more important for in vitro intramacrophage growth and mouse virulence than the Tfp component pilE4. Our results provide the first genetic characterization of the novel Tfp system of F. tularensis. INTRODUCTIONFrancisella tularensis is a highly infectious bacterium that causes tularaemia. F. tularensis is found in many different animal hosts and can be transmitted by arthropod vectors (Ellis et al., 2002). Humans can acquire the bacteria by a number of different routes, but inhalation of low doses of the organism can lead to a serious pneumonic form of disease that has a high mortality rate, and this has led to the classification of this bacterium as a category A biothreat agent (Dennis et al., 2001). F. tularensis is further divided into different subspecies (Oyston et al., 2004). F. tularensis subsp. tularensis has historically been associated with bioweapons development, and is reported to have the highest virulence for humans (McLendon et al., 2006). F. tularensis subsp. holarctica is also infectious in humans but typically with a less severe outcome (Sjostedt, 2003). An attenuated 'live vaccine strain' (LVS) was derived by repeated passage of subsp. holarctica in the laboratory; despite the unclear nature of the attenuating mutation(s) in this strain, it is frequently used as a laboratory model for tularaemia (Anthony & Kongshavn, 1987;Eigelsbach et al., 1951). F. tularensis subsp. novicida has low virulence for humans, but maintains high virulence in mice (Kieffer et al., 2003;Lauriano et al., 2004). Whole-genome sequencing has revealed that all three subspecies are closely related, with the less virulent (for humans) subsp. novicida showing less genomic decay than the more virulent subsp. holarctica and subsp. tularensis (Larsson et al., 2005;Petrosino et al., 2006;Rohmer et al., 2006).The ability of F. tularensis to survive and replicate within macrophages has been linked to its virulence (Anthony et al., 19...

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“…Despite being as infectious as biotype A, the lower virulence of the European biotype B enables laboratory work under containment level three conditions (Tarnvik and Berglund, 2003). Nevertheless, most experimental studies during the last three decades have used not virulent clinical isolates but the live vaccine strain (LVS) of F. tularensis attenuated for humans (Anthony and Kongshavn, 1987;Conlan et al, 1994;Green et al, 2005). However, there are genuine concerns about using F. tularensis LVS as a surrogate for more virulent strains of the pathogen .…”

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confidence: 99%

Susceptibility of selected murine and microtine species to infection by a wild strain of Francisella tularensis subsp. holoarctica

Banďouchová¹,

Sedláčková²,

Hubálek³

et al. 2009

Vet. Med. - Czech

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ABSTRACT:The purpose of this study was to compare susceptibility of BALB/c mice, common voles (Microtus arvalis) and yellow-necked mice (Apodemus flavicollis) to infection by a virulent Francisella tularensis subsp. holarctica strain. Median survival in these three species following experimental infection with 320 colony forming units of F. tularensis (both intraperitoneally and subcutaneously) amounted to 4.5, 7 and 4 days, respectively. Survival curves of BALB/c and yellow-necked mice were very similar and were significantly different from that of common voles. LD 50 was 0.5 and 37.9 colony forming units in BALB/c mice and common voles, respectively. The bacterial burden in the spleen, liver, lung, kidney and blood of common voles started to develop later post exposure and amounted to lower levels (except in kidneys) than in BALB/c mice. The results demonstrate that yellow-necked mice are even more susceptible to infection by F. tularensis than BALB/c mice and that the common vole is a small mammalian host with a susceptibility which is two-orders-of-magnitude lower.

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Experimental murine tularemia caused by Francisella tularensis, live vaccine strain: a model of acquired cellular resistance

Cited by 75 publications

References 26 publications

Purified Lipopolysaccharide fromFrancisella tularensisLive Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon

Purified Lipopolysaccharide fromFrancisella tularensisLive Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon

Characterization of the Francisella tularensis subsp. novicida type IV pilus

Susceptibility of selected murine and microtine species to infection by a wild strain of Francisella tularensis subsp. holoarctica

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