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Karlsson, Stefan
Publications (5 of 5) Show all publications
Gustafsson, E., Karlsson, S., Oscarsson, J., Sögård, P., Nilsson, P. & Arvidson, S. (2009). Mathematical modelling of the regulation of spa (protein A) transcription in Staphylococcus aureus. International Journal of Medical Microbiology, 299(1), 65-74
Open this publication in new window or tab >>Mathematical modelling of the regulation of spa (protein A) transcription in Staphylococcus aureus
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2009 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 299, no 1, p. 65-74Article in journal (Refereed) Published
Abstract [en]

In the present work a general systems biology approach has been used to study the complex regulatory network controlling the transcription of the spa gene, encoding protein A, a major surface protein and an important virulence factor of Staphylococcus aureus. A valid mathematical model could be formulated using parameter values, which were fitted to quantitative Northern blot data from various S. aureus regulatory mutants using a gradient search method. The model could correctly predict spa expression levels in 4 different regulatory mutants not included in the parameter value search, and in 2 other S. aureus strains, SH 1000 and UAMS-1. The mathematical model revealed that sarA and sarS seem to balance each other in a way that when the activating impact of sarS is small, e.g. in the wild-type, the repressive impact of sarA is small, while in an agr-deficient background, when the impact of sarS is maximal, the repressive impact of sarA is close to its maximum. Furthermore, the model revealed that Rot and SarS act synergistically to stimulate spa expression, something that was not obvious from experimental data. We believe that this mathematical model can be used to evaluate the significance of other putative interactions in the regulatory network governing spa transcription. (C) 2008 Elsevier GmbH. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2009
Identifiers
urn:nbn:se:his:diva-7832 (URN)10.1016/j.ijmm.2008.05.011 (DOI)000263074400007 ()18657473 (PubMedID)2-s2.0-56949084305 (Scopus ID)
Available from: 2013-03-28 Created: 2013-03-21 Last updated: 2017-12-06Bibliographically approved
Jansson, A., Harlén, M., Karlsson, S., Nilsson, P. & Cooley, M. (2007). 3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance. Immunology and Cell Biology, 85(3), 189-196
Open this publication in new window or tab >>3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance
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2007 (English)In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 85, no 3, p. 189-196Article in journal (Refereed) Published
Abstract [en]

Th-cell development has been suggested to include selective mechanisms in which certain cytokines select either Th1 or Th2 cells to proliferate and grow. The selective theory is based on the observation that Th2 cells secrete IL-4, a cytokine that promotes Th2 development, whereas Th1 cells secrete interferon-gamma (IFN-italic gamma) that favours Th1 development, and both positive and negative selective influences have been suggested to operate. In this study, we investigate the role of autocrine secretion and utilization of IL-4 by Th2 cells and address the question of whether an activated Th2 cell can be positively selected by IL-4 secreted from other Th2 cells. We present a spatial three dimensional (3D) modelling approach to simulate the interaction between the IL-4 ligand and its IL-4 receptors expressed on discrete IL-4 secreting cells. The simulations, based on existing experimental data on the IL-4 receptor–ligand system, illustrate how Th-cell development is highly dependent on the distance between cells that are communicating. The model suggests that a single Th2 cell is likely to communicate with possible target cells within a range of approximately 100 mum and that an activated Th2 cell manages to fill most of its own IL-4 receptors, even at a low secretion rate. The predictions made by the model suggest that negative selection against Th1 cells is more effective than positive selection by IL-4 for promoting Th2 dominance.

Place, publisher, year, edition, pages
Nature Publishing Group, 2007
Keywords
simulation, IL-4, diffusion, differentiation
Identifiers
urn:nbn:se:his:diva-2034 (URN)10.1038/sj.icb.7100023 (DOI)000246427900005 ()17199110 (PubMedID)2-s2.0-34247868910 (Scopus ID)
Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2017-12-12Bibliographically approved
Karlsson, D., Karlsson, S., Gustafsson, E., Henriques Normark, B. & Nilsson, P. (2007). Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae. Biosystems (Amsterdam. Print), 90(1), 211-223
Open this publication in new window or tab >>Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae
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2007 (English)In: Biosystems (Amsterdam. Print), ISSN 0303-2647, E-ISSN 1872-8324, Vol. 90, no 1, p. 211-223Article in journal (Refereed) Published
Abstract [en]

Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures.

Place, publisher, year, edition, pages
Elsevier, 2007
Identifiers
urn:nbn:se:his:diva-1887 (URN)10.1016/j.biosystems.2006.08.005 (DOI)000248966800019 ()17011700 (PubMedID)2-s2.0-34447093989 (Scopus ID)
Available from: 2007-09-19 Created: 2007-09-19 Last updated: 2020-02-14Bibliographically approved
Gustafsson, E., Nilsson, P., Karlsson, S. & Arvidson, S. (2005). Characterizing the Dynamics of the Quorum-Sensing System in Staphylococcus aureus. Journal of Molecular Microbiology and Biotechnology, 8(4), 232-242
Open this publication in new window or tab >>Characterizing the Dynamics of the Quorum-Sensing System in Staphylococcus aureus
2005 (English)In: Journal of Molecular Microbiology and Biotechnology, ISSN 1464-1801, Vol. 8, no 4, p. 232-242Article in journal (Refereed) Published
Abstract [en]

The virulence determinants of Staphylococcus aureus are expressed in a growth phase-dependent manner governed by the autoinducible quorum-sensing system agr. Activation of the agr system results in a rapid increase in the regulator RNAIII and occurs in response to accumulation of AIP. In order to activate the agr system, a basal transcription of agr components must be assumed. This basal transcription of agr components seems to be stimulated by sarA. To better understand how SarA would affect activation of the agr system by modulating the basal agr activity, a mathematical model for autoactivation of the agr system was set up. The model predicted that the agr system is hysteretic, meaning that the agr system is activated at a specific concentration of autoinducing peptide (AIP), whereas it is inactivated at a specific lower concentration of AIP. According to the model, changing the basal agr activity only had a marginal effect on steady-state levels of RNAIII but changed the sensitivity of the cells to AIP. This was supported by Northern blot analysis of RNAIII in S. aureus mutants with different levels of SarA expression. Since natural antagonistic AIPs have been demonstrated, the effect of adding inhibitors to the system was analyzed.

Place, publisher, year, edition, pages
S. Karger, 2005
Identifiers
urn:nbn:se:his:diva-1670 (URN)10.1159/000086704 (DOI)000232082700005 ()16179800 (PubMedID)2-s2.0-25444505009 (Scopus ID)
Available from: 2007-08-08 Created: 2007-08-08 Last updated: 2017-11-27Bibliographically approved
Karlsson, S. (1998). Topics on cubic hypersurfaces. (Doctoral dissertation). Matematik och Datavetenskap GU/CTH
Open this publication in new window or tab >>Topics on cubic hypersurfaces
1998 (English)Doctoral thesis, monograph (Other academic)
Place, publisher, year, edition, pages
Matematik och Datavetenskap GU/CTH, 1998
National Category
Geometry
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-9913 (URN)91-7197-662-0 (ISBN)
Public defence
1998-06-05, 20:41 (Swedish)
Opponent
Supervisors
Available from: 2014-09-30 Created: 2014-09-08 Last updated: 2017-11-27Bibliographically approved
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