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| 2. |
- Andersson, Henrik, et al.
(författare)
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T A microarray analysis of the murine macrophage response to infection with Francisella tularensis LVS
- 2006
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 55:8, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- The response of cells of the mouse macrophage cell line J774 to infection with Francisella tularensis LVS was analysed by means of a DNA microarray representing approximately 18 500 genes (20 600 clones). The adaptive response was modest at all time points, and at most, 81 clones were differentially regulated from the time point of uptake of bacteria (0 min) up to 240 min later. For all five time points, 229 clones fulfilled the criteria of being differentially regulated, i.e. the ratio between infected versus non-infected cells was at least 1.7-fold up- or down-regulated and P <0.05. It was found that many of the differentially regulated genes are known to respond to stress in general and to oxidative stress specifically. However, at 120 min it was observed that genes that lead to depletion of glutathione were upregulated. Possibly, this was a result of mechanisms induced by F. tularensis. Generally, there was a conspicuous lack of inflammatory responses and, for example, although tumour necrosis factor alpha (TNF-α) was upregulated at 0 min, a significant down-regulation was noted at all subsequent time points. When cells were treated with an inhibitor of inducible nitric oxide synthase (iNOS) or the antioxidant N-acetylcysteine (NAC), the infection-induced cytopathogenic effect was significantly inhibited. Together, the results suggest that F. tularensis LVS infection confers an oxidative stress upon the target cells and that many of the host-defence mechanisms appear to be intended to counteract this stress. The infection is characterized by a very modest inflammatory response.
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| 3. |
- Forslund, Anna-Lena, 1964-, et al.
(författare)
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Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis
- 2006
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Ingår i: Molecular Microbiology. - : Wiley-Blackwell. - 0950-382X .- 1365-2958. ; 59:6, s. 1818-1830
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis, the causative agent of tularaemia, is a highly infectious and virulent intracellular pathogen. There are two main human pathogenic subspecies, Francisella tularensis ssp. tularensis (type A), and Francisella tularensis ssp. holarctica (type B). So far, knowledge regarding key virulence determinants is limited but it is clear that intracellular survival and multiplication is one major virulence strategy of Francisella. In addition, genome sequencing has revealed the presence of genes encoding type IV pili (Tfp). One genomic region encoding three proteins with signatures typical for type IV pilins contained two 120 bp direct repeats. Here we establish that repeat-mediated loss of one of the putative pilin genes in a type B strain results in severe virulence attenuation in mice infected by subcutaneous route. Complementation of the mutant by introduction of the pilin gene in cis resulted in complete restoration of virulence. The level of attenuation was similar to that of the live vaccine strain and this strain was also found to lack the pilin gene as result of a similar deletion event mediated by the direct repeats. Presence of the pilin had no major effect on the ability to interact, survive and multiply inside macrophage-like cell lines. Importantly, the pilin-negative strain was impaired in its ability to spread from the initial site of infection to the spleen. Our findings indicate that this putative pilin is critical for Francisella infections that occur via peripheral routes.
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| 4. |
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| 5. |
- Forslund, Anna-Lena, 1964-, et al.
(författare)
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The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis
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Annan publikation (populärvet., debatt m.m.)abstract
- Background: All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene.Results: In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several pilin genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type.Conclusions: This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model.
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| 6. |
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| 7. |
- Gylfe, Åsa, et al.
(författare)
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Isolation of Lyme disease Borrelia from puffins (Fratercula arctica) and seabird ticks (Ixodes uriae) on the Faeroe Islands
- 1999
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 37:4, s. 890-896
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Tidskriftsartikel (refereegranskat)abstract
- This is the first report on the isolation of Lyme disease Borrelia from seabirds on the Faeroe Islands and the characteristics of its enzootic cycle. The major components of the Borrelia cycle include the puffin (Fratercula arctica) as the reservoir and Ixodes uriae as the vector. The importance of this cycle and its impact on the spread of human Lyme borreliosis have not yet been established. Borrelia spirochetes isolated from 2 of 102 sampled puffins were compared to the borreliae previously obtained from seabird ticks, I. uriae. The rrf-rrl intergenic spacer and the rrs and the ospC genes were sequenced and a series of phylogenetic trees were constructed. Sequence data and restriction fragment length polymorphism analysis grouped the strains together with Borrelia garinii. In a seroepidemiological survey performed with residents involved in puffin hunting on the Faeroe Islands, 3 of 81 serum samples were found to be positive by two commonly used clinical tests: a flagellin-based enzyme-linked immunosorbent assay (ELISA) and Western blotting. These three positive serum samples also had high optical density values in a whole-cell ELISA. The finding of seropositive Faeroe Islanders who are regularly exposed to I. uriae indicate that there may be a transfer of B. garinii by this tick species to humans.
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| 9. |
- Jaenson, Thomas G. T., et al.
(författare)
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The ecology of lyme borreliosis in Sweden
- 1994. - 1
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Ingår i: Lyme borreliosis. - New York : Springer-Verlag New York. - 9781461524151 ; , s. 113-115
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The geographical distribution of Lyme borreliosis (Lb) in the North European countries appears to coincide with the geographical distribution of the principal vector, the common tick Ixodes ricinus. We have found that in Sweden this tick species occurs in the southern and south-central parts of the country and along the coast of northern Sweden. This area corresponds with the distributional area of Lyme borreliosis. I. ricinus, and thus also Borrelia burgdorferi s.l., are in general not present in the interior of North Sweden, presumably because the climate is too harsh for the vector.
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| 10. |
- Johansson, Anna-Lena, et al.
(författare)
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Francisella
- 2015. - 2
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Ingår i: Molecular medical microbiology. - : Academic Press. - 9780123971692 - 9780123977632 ; , s. 1991-2009
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Bokkapitel (refereegranskat)abstract
- Francisella tularensis, the causative agent of tularaemia, is a zoonotic intracellular pathogen that can be found in a very large number of species ranging from large mammals and vertebrates to invertebrates, arthropods and amoebas. Disease in humans often occurs in parallel with tularaemia in wild animals. Human infection can occur through aerosolization, direct contact with infected animals via arthropod vectors like ticks, mosquitos and biting flies. F. tularensis subspecies tularensis (type A) is one of the most infectious bacteria known and inhalation of as few as ten organisms can be sufficient to establish an infection in humans that if left untreated could be fatal. The success of F. tularensis as a pathogen lies in its unique ability to adapt a lifestyle as an intracellular pathogen and to very timely subvert host defences both at extracellular and intracellular levels. Key events in the infection process are the ability to rapidly escape the phagosome after uptake by phagocytic cells and the ability to replicate to high levels inside the host cells without evoking a host inflammatory response.
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