| 1. |
- Bergsten, Göran, et al.
(författare)
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Do type 1 fimbriae promote inflammation in the human urinary tract?
- 2007
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 9:7, s. 1766-1781
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.
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| 2. |
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| 3. |
- Bergsten, Göran
(författare)
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Escherichia coli Fimbriae, Bacterial Persistence and Host Response Induction in the Human Urinary Tract
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections (UTI) are among the most common bacterial infections in humans. Symptomatic UTIs may be acute, recurrent or chronic but the most frequent form of UTI is asymptomatic bacteruria (ABU). In ABU, the mucosa remains inert, despite the presence of large bacterial numbers in urine. The difference in disease severity reflects the virulence of the infecting strain and the propensity of the host to respond to infection. It is essential to understand the molecular basis of disease diversity and the molecular interactions between bacteria and host that determine asymptomatic carriage and the transition to disease. This thesis concerns the initial interactions between bacteria with the mucosal surfaces in the human urinary tract, and the bacterial factors involved in the breach of mucosal inertia. Specifically, the contribution of P and type 1 fimbriae to bacterial establishment and host response induction are investigated. The human bacteriuria model was used, since ABU protects against infections with more virulent strains. To study the role of adherence in UTI an Escherichia coli ABU strain, which does not express adherence factors, was transformed with DNA sequences encoding P or type 1 fimbriae and used for deliberate inoculation of patients with a history of recurrent UTI. P fimbriae were shown to provide a colonization advantage during the first days of bacterial establishment, as compared to the ABU strain lacking P fimbriae. In addition, P fimbriated E. coli were shown to trigger the innate mucosal responses, with increases in urine IL-6 and IL-8 concentrations, and recruitment of neutrophils. This effect was adhesion dependent, as shown by inoculations with a P fimbriated mutant lacking the PapG, adhesin. The P fimbriated bacteria adhered to uroepithelial cells in vivo, but adherence was not observed with the papG deletion mutant. After similar inoculations, type 1 fimbriae were not found to help the establishment of bacteriuria or the mucosal host response in the human urinary tract. This is surprising as type 1 fimbriae have been identified as important virulence factors in animal models of UTI. The results show that P fimbriae serve as independent virulence factors when expressed by an ABU strain, by promoting the establishment of bacteriuria and the innate host response, which is the cause of symptoms and tissue damage. P fimbriae thus fulfil the molecular Koch postulates as independent virulence factors in the human urinary tract. Type 1 fimbriae, in contrast, did not act as virulence factors in this model, and thus appear to serve a different function in man.
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| 4. |
- Bergsten, Göran, et al.
(författare)
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PapG-dependent adherence breaks mucosal inertia and triggers the innate host response
- 2004
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 189:9, s. 1734-1742
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal pathogens differ from normal flora constituents in that they provoke a host response that upsets mucosal integrity. We investigated whether the elaboration of discrete adherence factors is sufficient to break the inertia of the mucosal barrier. PapG-mediated adherence was selected as an example, because P fimbrial expression characterizes uropathogenic Escherichia coli and because adherence starts the attack on the mucosal barrier. Patients were inoculated intravesically with transformed nonvirulent E. coli strains expressing functional P fimbriae (E. coli pap(+)) or mutant fimbriae lacking the adhesin (E. coli DeltapapG). E. coli pap(+) was shown to activate the innate host response, and adherent gfp(+) bacteria were observed on excreted uroepithelial cells. E. coli DeltapapG failed to trigger a response and was nonadhesive. We conclude that PapG-mediated adherence breaks mucosal inertia in the human urinary tract by triggering innate immunity and propose that this activation step differentiates asymptomatic carriage from infection.
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| 5. |
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| 6. |
- Godaly, Gabriela, et al.
(författare)
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Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection
- 2001
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Ingår i: Journal of Leukocyte Biology. - 1938-3673. ; 69:6, s. 899-906
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.
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| 7. |
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| 8. |
- Hallsby, Göran, et al.
(författare)
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Effects of intensity of forest regeneration measures on stand development in a nationwide Swedish field experiment
- 2015
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Ingår i: Forestry. - : Oxford University Press (OUP). - 0015-752X .- 1464-3626. ; 88, s. 441-453
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Tidskriftsartikel (refereegranskat)abstract
- The general belief that intense regeneration measures are financially viable and essential for high sustained yields of commercial forest products has been inadequately tested. This field experiment evaluates effects of three different regeneration intensities 24-27 years after clear-cutting of 14 sites across Sweden. The treatments, designated high (HI), normal (NI) and low (LI), respectively, consisted of: mechanical site preparation and planting of large seedlings at 2x2 m spacing, with supplemental planting and pre-commercial thinning (PCT) when deemed necessary; standard local practices; and natural regeneration with no site preparation, artificial regeneration or PCT. Average crop seedling densities were highest and lowest (3359 and 1662 ha(-1)) under the HI and LI treatments, respectively, 4-8 growing seasons after planting. After 24-27 years, HI also resulted in higher mean stem volume (90 m(3) ha(-1)) than LI (36 m3 ha 21) but was not significantly different from NI (65 m(3) ha(-1)) and increasing the regeneration intensity was not consistently positive. In some cases, high planted seedling mortality and generally abundant natural regeneration resulted in minor (or no) differences between the treatments. The results illustrate that current Swedish regeneration standards may need revision in order to reflect contemporary societal and commercial demands.
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| 9. |
- Hauksson, Jón B, et al.
(författare)
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Prediction of basic wood properties for Norway spruce. Interpretation of Near Infrared Spectroscopy data using partial least squares regression
- 2001
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Ingår i: Wood Science and Technology. - : Springer Science and Business Media LLC. - 0043-7719 .- 1432-5225. ; 35:6, s. 475-85
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Tidskriftsartikel (refereegranskat)abstract
- This work was undertaken to investigate the feasibility of using near infrared spectroscopy (NIR) and partial least squares regression (PLS) as a tool to characterize the basic wood properties of Norway Spruce (Picea abies (L.) Karst.). The wood samples originated from a trial located in the province of Västerbotten in Sweden. In this trial, the effects of birch shelterwoods (Betula pendula Roth) of different densities on growth and yield in Norway spruce understorey were examined. All Norway spruce trees in each shelterwood treatment were divided into three growth rate classes based on diameter at breast height (1.3 m) over bark. Five discs were cut from each tree (i.e. from the root stem, and at 20%, 40%, 60%, and 80% of the total height). The discs from 40% tree height were used (i.e., where the largest variations in annual ring widths and wood density were found). A total of 27 discs were selected. The discs were used for measuring annual ring widths, wood density, average fiber length and the fiber length distributions. Milled wood samples prepared from the discs were used for recording NIR spectra. PLS regression was used to generate prediction models for the wood properties (Y-matrix) and NIR spectra (X-matrix) as well as between the wood properties (Y-matrix) and the fiber length distributions (X-matrix). One set of models was generated using untreated spectra and fiber length distributions. For a second set of models the structure in the X-matrix, which was orthogonal to the matrix described by the wood properties, was eliminated using a soft target rotation technique called orthogonal signal correction (OSC). The PLS model obtained using "raw" untreated NIR spectra and fiber length distributions had a poor modeling power as evidenced by the cumulative Q2 values. For the PLS models based on untreated NIR spectra the cumulative Q2 values ranged from a minimum of 16% (wood density) to a maximum of 46% (no. of annual rings). Orthogonal signal correction of the X-matrix (NIR spectra or fiber length distributions) gave PLS models with a modeling power corresponding to cumulative Q2 values well in excess of 70%. The improvement in predictive ability accomplished by the OSC procedure was verified by placing four of the 27 observations in an external test set and comparing RMSEP values for the test set observations without OSC and with OSC.
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