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Lindberg, Stina
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Publications (10 of 10) Show all publications
Tükenmez, H., Edström, I., Kalsum, S., Braian, C., Ummanni, R., Lindberg, S., . . . Larsson, C. (2019). Corticosteroids protect infected cells against mycobacterial killing in vitro. Biochemical and Biophysical Research Communications - BBRC, 511(1), 117-121
Open this publication in new window or tab >>Corticosteroids protect infected cells against mycobacterial killing in vitro
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2019 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 511, no 1, p. 117-121Article in journal (Refereed) Published
Abstract [en]

The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent cytolysis of fibroblasts infected with mycobacteria. Further experiments with Mycobacterium tuberculosis showed anti-cytolytic activity in the 10 nM range, but no effect on bacterial growth or survival in the absence of host cells at 20 mu M. The results from a panel of corticosteroids with various affinities to the glucocorticoid- and mineralocorticoid receptors indicate that the inhibition of cytolysis most likely is mediated through the glucocorticoid receptor. Using live-imaging of M. tuberculosis-infected human monocyte-derived macrophages, we also show that corticosteroids to some extent control intracellular bacteria. In vitro systems with reduced complexity are to further study and understand the interactions between bacterial infection, immune defense and cell signaling. (C) 2019 The Authors. Published by Elsevier Inc.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019
Keywords
Mycobacterium, Tuberculosis, Corticosteroids, Cell death, Drug discovery
National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-157508 (URN)10.1016/j.bbrc.2019.02.044 (DOI)000460849800019 ()30773257 (PubMedID)
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved
Muheim, C., Götzke, H., Eriksson, A. U., Lindberg, S., Lauritsen, I., Nørholm, M. H. H. & Daley, D. O. (2017). Increasing the permeability of Escherichia coli using MAC13243. Scientific Reports, 7, Article ID 17629.
Open this publication in new window or tab >>Increasing the permeability of Escherichia coli using MAC13243
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17629Article in journal (Refereed) Published
Abstract [en]

The outer membrane of gram-negative bacteria is a permeability barrier that prevents the efficient uptake of molecules with large scaffolds. As a consequence, a number of antibiotic classes are ineffective against gram-negative strains. Herein we carried out a high throughput screen for small molecules that make the outer membrane of Escherichia coli more permeable. We identified MAC13243, an inhibitor of the periplasmic chaperone LolA that traffics lipoproteins from the inner to the outer membrane. We observed that cells were (1) more permeable to the fluorescent probe 1-N-phenylnapthylamine, and (2) more susceptible to large-scaffold antibiotics when sub-inhibitory concentrations of MAC13243 were used. To exclude the possibility that the permeability was caused by an off-target effect, we genetically reconstructed the MAC13243-phenotype by depleting LolA levels using the CRISPRi system.

Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2017
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-143193 (URN)10.1038/s41598-017-17772-6 (DOI)000418250800014 ()29247166 (PubMedID)
Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2018-06-09Bibliographically approved
Sullivan Hellgren, J. & Lindberg, S. (2017). Motivating students with authentic science experiences: changes in motivation for school science. Research in Science & Technological Education, 35(4), 409-426
Open this publication in new window or tab >>Motivating students with authentic science experiences: changes in motivation for school science
2017 (English)In: Research in Science & Technological Education, ISSN 0263-5143, E-ISSN 1470-1138, Vol. 35, no 4, p. 409-426Article in journal (Refereed) Published
Abstract [en]

Background: Students' motivation for science declines over the early teenage years, and students often find school science difficult and irrelevant to their everyday lives. This paper asks whether creating opportunities to connect school science to authentic science can have positive effects on student motivation.

Purpose: To understand how authentic science experiences can affect students' motivation for science and students’ goals, values, beliefs and attitudes towards science.

Programme description: The Medicine Hunt brought scientists and students together to find bacteria that produce secondary metabolites with antibiotic effects. Scientists received help with collecting soil samples and teachers and students took an active role in research and worked with solving an authentic problem as a part of their ordinary school science over a course of six months.

Sample: About 388 students from 18 lower-secondary school classes participating in the Medicine Hunt. Students were enrolled in grade seven to nine (13–15 years old). At this stage, science is compulsory, and all students follow the same science course. The classes represented different geographical regions of Sweden.

Design and methods: Students filled in motivation questionnaires before and after the Medicine Hunt. Paired t-tests were used to evaluate how students’ intrinsic motivation, goals, values, beliefs and attitudes towards science changed over the project period.

Results: Students' intrinsic motivation for school science and plans for future participation in science remained unchanged during the period they participated in the Medicine Hunt, and students' goals, values and attitudes followed the well-documented pattern of decline. Thus, the authentic experience can arrest the well-described decline for some motivation-related factors.

Conclusions: The findings suggest that the authentic experience can arrest some aspects of the decline in motivation for science in the teenage years. The paper discusses the processes around students' motivation in relation to authentic experiences.

Place, publisher, year, edition, pages
Abingdon: Taylor & Francis, 2017
Keywords
motivation, authentic science, student-teacher-scientist partnership, secondary school
National Category
Pedagogical Work
Research subject
didactics of natural science
Identifiers
urn:nbn:se:umu:diva-120039 (URN)10.1080/02635143.2017.1322572 (DOI)000413984600003 ()
Projects
Lärandesituationens påverkan på elevers affektiva upplevelser och lärande
Funder
Swedish Research Council, 2007-3216
Note

Originally published in thesis in manuscript form.

Available from: 2016-05-09 Created: 2016-05-05 Last updated: 2018-06-07Bibliographically approved
Andresen, L., Varik, V., Tozawa, Y., Jimmy, S., Lindberg, S., Tenson, T. & Hauryliuk, V. (2016). Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors. Scientific Reports, 6, Article ID 35824.
Open this publication in new window or tab >>Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35824Article in journal (Refereed) Published
Abstract [en]

The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy) alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors-a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

National Category
Microbiology Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-127600 (URN)10.1038/srep35824 (DOI)000385923600001 ()27775002 (PubMedID)
Available from: 2016-12-07 Created: 2016-11-16 Last updated: 2018-06-09Bibliographically approved
Decker, D., Lindberg, S., Eriksson, J. & Kleczkowski, L. A. (2014). A luminescence-based assay of UDP-sugar producing pyrophosphorylases. Analytical Methods, 6(1), 57-61
Open this publication in new window or tab >>A luminescence-based assay of UDP-sugar producing pyrophosphorylases
2014 (English)In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 6, no 1, p. 57-61Article in journal (Refereed) Published
Abstract [en]

A coupled luminescence assay was applied to monitor pyrophosphate (PPi) production by either purified barley UDP-glucose pyrophosphorylase (UGPase) or purified Leishmania UDP-sugar pyrophosphorylase (USPase). In the assay, the PPi produced by the pyrophosphorylases was converted to ATP by ATP-sulfurylase, and the ATP produced was linked to luminescent light formation through the action of firefly luciferase. The assay allowed for a quantitative measurement of UGPase and USPase activities, down to a pmol per min level. The activities were linear with time and proportional to the amount of the enzyme added, and were neither affected by Pi nor by DTT. For UGPase, K-m values with UTP and Glc-1-P were 0.14 and 0.26 mM, respectively, whereas for USPase the respective K-m values with UTP, Glc-1-P and Gal-1-P were 0.4, 2.9 and 3.9 mM. Possible applications of the luminescence-based assay for not only UDP-sugar producing pyrophosphorylases, but also other types of pyrophosphorylases are discussed.

National Category
Chemical Sciences Botany
Identifiers
urn:nbn:se:umu:diva-85622 (URN)10.1039/C3AY41811a (DOI)000329071500004 ()
Funder
Swedish Research Council
Available from: 2014-02-10 Created: 2014-02-07 Last updated: 2018-06-08Bibliographically approved
Castelain, M., Ehlers, S., Klinth, J., Lindberg, S., Andersson, M., Uhlin, B. E. & Axner, O. (2011). Fast uncoiling kinetics of F1C pili expressed by uropathogenic Escherichia coli are revealed on a single pilus level using force-measuring optical tweezers. European Biophysics Journal, 40(3), 305-316
Open this publication in new window or tab >>Fast uncoiling kinetics of F1C pili expressed by uropathogenic Escherichia coli are revealed on a single pilus level using force-measuring optical tweezers
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2011 (English)In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 40, no 3, p. 305-316Article in journal (Refereed) Published
Abstract [en]

Uropathogenic Escherichia coli (UPEC) expressvarious kinds of organelles, so-called pili or fimbriae, thatmediate adhesion to host tissue in the urinary tract throughspecific receptor-adhesin interactions. The biomechanicalproperties of these pili have been considered important forthe ability of bacteria to withstand shear forces from rinsingurine flows. Force-measuring optical tweezers have beenused to characterize individual organelles of F1C typeexpressed by UPEC bacteria with respect to such properties.Qualitatively, the force-versus-elongation response wasfound to be similar to that of other types of helix-like piliexpressed by UPEC, i.e., type 1, P, and S, with force-inducedelongation in three regions, one of which represents theimportant uncoiling mechanism of the helix-like quaternarystructure. Quantitatively, the steady-state uncoiling forcewas assessed as 26.4 ±1.4 pN, which is similar to those ofother pili (which range from 21 pN for SI to 30 pN for type 1).The corner velocity for dynamic response (1,400 nm/s) wasfound to be larger than those of the other pili (400–700 nm/sfor S and P pili, and 6 nm/s for type 1). The kinetics werefound to be faster, with a thermal opening rate of 17 Hz, afew times higher than S and P pili, and three orders ofmagnitude higher than type 1. These data suggest that F1Cpili are, like P and S pili, evolutionarily selected to primarilywithstand the conditions expressed in the upper urinary tract.

Keywords
optical tweezers, force spectroscopy, pili, bacteria, adhesion
National Category
Other Physics Topics Condensed Matter Physics Cell and Molecular Biology Microbiology in the medical area Microbiology in the medical area
Research subject
Mathematics; Physics; Microbiology
Identifiers
urn:nbn:se:umu:diva-38646 (URN)10.1007/s00249-010-0648-1 (DOI)
Available from: 2010-12-20 Created: 2010-12-20 Last updated: 2018-06-08Bibliographically approved
Wikström Hultdin, U., Lindberg, S., Grundström, C., Allgardsson, A., Huang, S., Stier, G., . . . Sauer-Eriksson, E. (2010). Purification, crystallization and preliminary data analysis of FocB, a transcription factor regulating fimbrial adhesin expression in uropathogenic Escherichia coli. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, 66(Pt 3), 337-341
Open this publication in new window or tab >>Purification, crystallization and preliminary data analysis of FocB, a transcription factor regulating fimbrial adhesin expression in uropathogenic Escherichia coli
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2010 (English)In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, ISSN 1744-3091, E-ISSN 1744-3091, Vol. 66, no Pt 3, p. 337-341Article in journal (Refereed) Published
Abstract [en]

The transcription factor FocB belongs to a family of regulators encoded by several different fimbriae gene clusters in uropathogenic Escherichia coli. Recent findings suggest that FocB-family proteins may form different protein-protein complexes and that they may exert both positive and negative effects on the transcription of fimbriae genes. However, little is known about the actual role and mode of action when these proteins interact with the fimbriae operons. The 109-amino-acid FocB transcription factor from the foc gene cluster in E. coli strain J96 has been cloned, expressed and purified. The His6-tagged fusion protein was captured by Ni2+-affinity chromatography, cleaved with tobacco etch virus protease and purified by gel filtration. The purified protein is oligomeric, most likely in the form of dimers. NMR analysis guided the crystallization attempts by showing that probable conformational exchange or oligomerization is reduced at temperatures above 293 K and that removal of the highly flexible His6 tag is advantageous. The protein was crystallized using the hanging-drop vapour-diffusion method at 295 K. A native data set to 2.0 Å resolution was collected at 100 K using synchrotron radiation.

Keywords
fimbriae, FocB, transcription factors
National Category
Chemical Sciences
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-27753 (URN)10.1107/S1744309110002204 (DOI)000275057700031 ()20208176 (PubMedID)
Available from: 2009-11-19 Created: 2009-11-19 Last updated: 2018-06-08Bibliographically approved
Wikström Hultdin, U., Lindberg, S., Grundström, C., Huang, S., Uhlin, B. E. & Sauer-Eriksson, E. (2010). Structure of FocB: a member of a family of transcription factors regulating fimbrial adhesin expression in uropathogenic Escherichia coli. The FEBS Journal, 277(16), 3368-3381
Open this publication in new window or tab >>Structure of FocB: a member of a family of transcription factors regulating fimbrial adhesin expression in uropathogenic Escherichia coli
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2010 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 277, no 16, p. 3368-3381Article in journal (Refereed) Published
Abstract [en]

In uropathogenic Escherichia coli, UPEC, different types of fimbriae are expressed in order to mediate interactions with host tissue. FocB belongs to the PapB family of transcription factors involved in the regulation of fimbriae gene clusters. Recent findings suggest that members from this family of proteins may form different protein-protein complexes and that they may exert both positive and negative effects on transcription of fimbriae genes. To elucidate the detailed function of FocB, we have determined its crystal structure at 1.4 Å resolution. FocB is an all alpha helical structure with a helix-turn-helix (HTH) motif. Interestingly, conserved residues important for DNA-binding are not located in the recognition helix of the HTH-motif, but in the preceding helix. Results from protein-DNA binding studies indicated that FocB interacts with minor groove of its cognate DNA, which also points to a DNA-interaction unusual for this motif. Packing interactions in the crystals gave two plausible dimerization interfaces. Conserved residues known to be important for protein oligomerization are present at both interfaces, suggesting that both sites play a role in a functional FocB protein.

Place, publisher, year, edition, pages
Wiley, 2010
Keywords
fimbriae, FocB, repressor protein, uropathogenic Escherichia coli, X-ray crystallography
National Category
Chemical Sciences
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-27755 (URN)10.1111/j.1742-4658.2010.07742.x (DOI)000280631300010 ()
Available from: 2009-11-19 Created: 2009-11-19 Last updated: 2018-06-08Bibliographically approved
Lindberg, S., Xia, Y., Sondén, B., Göransson, M., Hacker, J. & Uhlin, B. E. (2008). Regulatory Interactions among adhesin gene systems of uropathogenic Escherichia coli. Infection and Immunity, 76(2), 771-780
Open this publication in new window or tab >>Regulatory Interactions among adhesin gene systems of uropathogenic Escherichia coli
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2008 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 76, no 2, p. 771-780Article in journal (Refereed) Published
Abstract [en]

Uropathogenic Escherichia coli strain J96 carries multiple determinants for fimbrial adhesins. The regulatory protein PapB of P fimbriae has previously been implicated in potential coregulatory events. The focB gene of the F1C fimbria determinant is highly homologous to papB; the translated sequences share 81% identity. In this study we investigated the role of PapB and FocB in regulation of the F1C fimbriae. By using gel mobility shift assays, we showed that FocB binds to sequences in both the pap and foc operons in a somewhat different manner than PapB. The results of both in vitro cross-linking and in vivo oligomerization tests indicated that FocB could function in an oligomeric fashion. Furthermore, our results suggest that PapB and FocB can form heterodimers and that these complexes can repress expression of the foc operon. The effect of FocB on expression of type 1 fimbriae was also tested. Taken together, the results that we present expand our knowledge about a regulatory network for different adhesin gene systems in uropathogenic E. coli and suggest a hierarchy for expression of the fimbrial adhesins.

Keywords
Uropathogenic E. coli, PapB, FocB, F1C, fimbriae, pili, cross-talk
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:umu:diva-19587 (URN)10.1128/IAI.01010-07 (DOI)18039830 (PubMedID)
Available from: 2009-03-06 Created: 2009-03-06 Last updated: 2018-06-09Bibliographically approved
Balsalobre, C., Silván, J. M., Berglund, S., Mizunoe, Y., Uhlin, B. E. & Nyunt Wai, S. (2006). Release of the type I secreted α-haemolysin via outer membrane vesicles from Escherichia coli. Molecular Microbiology, 59(1), 99-112
Open this publication in new window or tab >>Release of the type I secreted α-haemolysin via outer membrane vesicles from Escherichia coli
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2006 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 59, no 1, p. 99-112Article in journal (Refereed) Published
Abstract [en]

The α-haemolysin is an important virulence factor commonly expressed by extraintestinal pathogenic Escherichia coli. The secretion of the α-haemolysin is mediated by the type I secretion system and the toxin reaches the extracellular space without the formation of periplasmic intermediates presumably in a soluble form. Surprisingly, we found that a fraction of this type I secreted protein is located within outer membrane vesicles (OMVs) that are released by the bacteria. The α-haemolysin appeared very tightly associated with the OMVs as judged by dissociation assays and proteinase susceptibility tests. The α-haemolysin in OMVs was cytotoxically active and caused lysis of red blood cells. The OMVs containing the α-haemolysin were distinct from the OMVs not containing α-haemolysin, showing a lower density. Furthermore, they differed in protein composition and one component of the type I secretion system, the TolC protein, was found in the lower density vesicles. Studies of natural isolates of E. coli demonstrated that the localization of α-haemolysin in OMVs is a common feature among haemolytic strains. We propose an alternative pathway for the transport of the type I secreted α-haemolysin from the bacteria to the host cells during bacterial infections.

Place, publisher, year, edition, pages
Hoboken, NJ, United States: Wiley-Blackwell, 2006
Keywords
Escherichia coli, OMVs, outer membrane vesicles, haemolysin, UPEC
National Category
Microbiology in the medical area
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-27736 (URN)10.1111/j.1365-2958.2005.04938.x (DOI)
Note
Stina Berglund nu Stina LindbergAvailable from: 2009-12-08 Created: 2009-11-18 Last updated: 2018-06-08Bibliographically approved
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