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Bergström, Sven
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Publications (10 of 95) Show all publications
Surowiec, I., Skotare, T., Sjögren, R., Gouveia-Figueira, S. C., Orikiiriza, J. T., Bergström, S., . . . Trygg, J. (2019). Joint and unique multiblock analysis of biological data: multiomics malaria study. Paper presented at Conference on Challenges in Analysis of Complex Natural Mixtures, Univ Edinburgh, Edinburgh, MAY 13-15, 2019. Faraday discussions (Online), 218, 268-283
Open this publication in new window or tab >>Joint and unique multiblock analysis of biological data: multiomics malaria study
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2019 (English)In: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 218, p. 268-283Article in journal (Refereed) Published
Abstract [en]

Modern profiling technologies enable obtaining large amounts of data which can be later used for comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be faced by bare analysis of separate datasets. Integrated approaches are necessary, because only data integration allows finding correlation trends common for all studied data sets and revealing hidden structures not known a priori. This improves understanding and interpretation of the complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variation shared with other connected matrices and variation that is unique for each single matrix. Mapping unique variation is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for integrated analysis of lipidomic, metabolomic and oxylipin datasets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, what makes development of the new diagnostic and prognostic tools, as well as better understanding of the disease, of utmost importance. In presented work JUMBA made it possible to detect already known trends related to disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced complexity of the analysis, facilitated detection of samples and variables corresponding to specific structures across multiple datasets and by doing this enabled fast interpretation of the studied system. All this makes JUMBA a perfect choice for multiblock analysis of systems biology data.

Place, publisher, year, edition, pages
Cambridge: Royal Society of Chemistry, 2019
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-156705 (URN)10.1039/C8FD00243F (DOI)000481497900014 ()
Conference
Conference on Challenges in Analysis of Complex Natural Mixtures, Univ Edinburgh, Edinburgh, MAY 13-15, 2019
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-11-14Bibliographically approved
Reuterswärd, P., Bergström, S., Orikiiriza, J., Lindquist, E., Bergström, S., Svahn, H. A., . . . Nilsson, P. (2018). Levels of human proteins in plasma associated with acute paediatric malaria. Malaria Journal, 17, Article ID 426.
Open this publication in new window or tab >>Levels of human proteins in plasma associated with acute paediatric malaria
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2018 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, article id 426Article in journal (Refereed) Published
Abstract [en]

Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts.

Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria.

Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Affinity proteomics, Human plasma profiling, Malaria, Plasmodium falciparum, suspension bead arrays, Sequestration, Cytoadhesion
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-154943 (URN)10.1186/s12936-018-2576-y (DOI)000450509700002 ()30442134 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-05-29Bibliographically approved
Bergström, S. & Normark, J. (2018). Microbiological features distinguishing Lyme disease and relapsing fever spirochetes. Wiener Klinische Wochenschrift, 130(15-16), 484-490
Open this publication in new window or tab >>Microbiological features distinguishing Lyme disease and relapsing fever spirochetes
2018 (English)In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 130, no 15-16, p. 484-490Article in journal (Refereed) Published
Abstract [en]

The recent proposal of splitting the genus Borrelia into two genera in the newly formed family of Borreliaceae, i.aEuro<overline>e. Borrelia and Borreliella has motivated us to reflect upon how these organisms has been characterized and differentiated. This article therefore aims to take a closer look on the biology and virulence attributes of the two suggested genera, i.aEuro<overline>e. those causing Lyme borreliosis and relapsing fever borreliosis. Both genera have much in common with similar infection biological features. They are both characterized as bacterial zoonoses, transmitted by hematophagous arthropods with almost identical microbiological appearance. Nevertheless, a closer look at the genotypic and phenotypic characteristics clearly reveals several differences that might motivate the suggested split. On the other hand, a change of this well-established classification within the genus Borrelia might impose an economical burden as well as a great confusion in society, including medical and scientific societies as well as the general population.

Place, publisher, year, edition, pages
SPRINGER WIEN, 2018
Keywords
Borrelia, Borreliella, Lyme borreliosis, Relapsing fever, Taxonomy
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-151059 (URN)10.1007/s00508-018-1368-2 (DOI)000441195100005 ()30074091 (PubMedID)
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-09-04Bibliographically approved
Surowiec, I., Johansson, E., Stenlund, H., Rantapää-Dahlqvist, S., Bergström, S., Normark, J. & Trygg, J. (2018). Quantification of run order effect on chromatography: mass spectrometry profiling data. Journal of Chromatography A, 1568, 229-234
Open this publication in new window or tab >>Quantification of run order effect on chromatography: mass spectrometry profiling data
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, p. 229-234Article in journal (Refereed) Published
Abstract [en]

Chromatographic systems coupled with mass spectrometry detection are widely used in biological studies investigating how levels of biomolecules respond to different internal and external stimuli. Such changes are normally expected to be of low magnitude and therefore all experimental factors that can influence the analysis need to be understood and minimized. Run order effect is commonly observed and constitutes a major challenge in chromatography-mass spectrometry based profiling studies that needs to be addressed before the biological evaluation of measured data is made. So far there is no established consensus, metric or method that quickly estimates the size of this effect. In this paper we demonstrate how orthogonal projections to latent structures (OPLS®) can be used for objective quantification of the run order effect in profiling studies. The quantification metric is expressed as the amount of variation in the experimental data that is correlated to the run order. One of the primary advantages with this approach is that it provides a fast way of quantifying run-order effect for all detected features, not only internal standards. Results obtained from quantification of run order effect as provided by the OPLS can be used in the evaluation of data normalization, support the optimization of analytical protocols and identification of compounds highly influenced by instrumental drift. The application of OPLS for quantification of run order is demonstrated on experimental data from plasma profiling performed on three analytical platforms: GCMS metabolomics, LCMS metabolomics and LCMS lipidomics.

Keywords
Run order effect quantification, Mass spectrometry profiling, OPLS, Instrumental drift
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-150428 (URN)10.1016/j.chroma.2018.07.019 (DOI)000443669600025 ()2-s2.0-85049727571 (Scopus ID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2019-05-29Bibliographically approved
Talagrand-Reboul, E., Boyer, P. H., Bergström, S., Vial, L. & Boulanger, N. (2018). Relapsing Fevers: Neglected Tick-Borne Diseases. Frontiers in Cellular and Infection Microbiology, 8, Article ID 98.
Open this publication in new window or tab >>Relapsing Fevers: Neglected Tick-Borne Diseases
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2018 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, article id 98Article, review/survey (Refereed) Published
Abstract [en]

Relapsing fever still remains a neglected disease and little is known on its reservoir, tick vector and physiopathology in the vertebrate host. The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family which also contain Lyme disease spirochaetes. They are mainly transmitted by Ornithodoros soft ticks, but some species are vectored by ixodid ticks. Traditionally a Borrelia species is associated with a specific vector in a particular geographical area. However, new species are regularly described, and taxonomical uncertainties deserve further investigations to better understand Borrelia vector/host adaptation. The medical importance of Borrelia miyamotoi, transmitted by Ixodes spp., has recently spawned new interest in this bacterial group. In this review, recent data on tick-host-pathogen interactions for tick-borne relapsing fevers is presented, with special focus on B. miyamotoi.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
relapsing fever, Borrelia, Ornithodoros, hard ticks, Borrelia miyamotoi, neurotropism, antigenic riations
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-148629 (URN)10.3389/fcimb.2018.00098 (DOI)000429178000002 ()29670860 (PubMedID)2-s2.0-85045051237 (Scopus ID)
Available from: 2018-06-21 Created: 2018-06-21 Last updated: 2018-06-21Bibliographically approved
Elbir, H., Sitlani, P., Bergström, S. & Barbour, A. G. (2017). Chromosome and Megaplasmid Sequences of Borrelia anserina (Sakharoff 1891), the Agent of Avian Spirochetosis and Type Species of the Genus. Genome Announcements, 5(11), Article ID e00018-17.
Open this publication in new window or tab >>Chromosome and Megaplasmid Sequences of Borrelia anserina (Sakharoff 1891), the Agent of Avian Spirochetosis and Type Species of the Genus
2017 (English)In: Genome Announcements, ISSN 2169-8287, E-ISSN 2169-8287, Vol. 5, no 11, article id e00018-17Article in journal (Refereed) Published
Abstract [en]

Sequences of the linear chromosome and plasmids of Borrelia anserina, the cause of avian spirochetosis of poultry, revealed a smaller genome than those of other Borrelia spp. transmitted by argasid ticks. Missing or disrupted genes included a dam methylase and those in the pathway for synthesis of phospholipids from glycerol.

Place, publisher, year, edition, pages
American Society for Microbiology, 2017
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-163053 (URN)10.1128/genomeA.00018-17 (DOI)000460686400005 ()28302772 (PubMedID)2-s2.0-85016418781 (Scopus ID)
Available from: 2019-09-09 Created: 2019-09-09 Last updated: 2019-09-09Bibliographically approved
Orikiiriza, J., Surowiec, I., Lindquist, E., Bonde, M., Magambo, J., Muhinda, C., . . . Normark, J. (2017). Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria. Metabolomics, 13(4), Article ID 41.
Open this publication in new window or tab >>Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
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2017 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 13, no 4, article id 41Article in journal (Refereed) Published
Abstract [en]

Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.

Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.

Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.

Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.

Keywords
Lipidomics profiling, Malaria, Plasmodium falciparum, Triacylglycerides, Lysophosphatidylcholines
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-133729 (URN)10.1007/s11306-017-1174-2 (DOI)000394544900010 ()28286460 (PubMedID)
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2018-06-09Bibliographically approved
Surowiec, I., Gouveia-Figueira, S., Orikiiriza, J., Lindquist, E., Bonde, M., Magambo, J., . . . Trygg, J. (2017). The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. Malaria Journal, 16, Article ID 358.
Open this publication in new window or tab >>The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
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2017 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, article id 358Article in journal (Refereed) Published
Abstract [en]

Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.

Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).

Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.

Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Oxylipins, Endocannabinoids, Malaria infection, Plasmodium falciparum
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-140041 (URN)10.1186/s12936-017-2001-y (DOI)000410218400001 ()28886714 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of Medicine
Note

Ytterligare finansiär: Jeansson Foundation

Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-06-09Bibliographically approved
Good, J. A. D., Kulén, M., Silver, J., Krishnan, K. S., Bahnan, W., Núñez-Otero, C., . . . Almqvist, F. (2017). Thiazolino 2-pyridone amide isosteres as inhibitors of Chlamydia trachomatis infectivity. Journal of Medicinal Chemistry, 60(22), 9393-9399
Open this publication in new window or tab >>Thiazolino 2-pyridone amide isosteres as inhibitors of Chlamydia trachomatis infectivity
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2017 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 60, no 22, p. 9393-9399Article in journal (Refereed) Published
Abstract [en]

Chlamydia trachomatis is a global health burden due to its prevalence as a sexually transmitted disease and as the causative agent of the eye infection trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated C. trachomatis infectivity without affecting host cell or commensal bacteria viability. We present here the synthesis and evaluation of nonhydrolyzable amide isosteres based on this class, leading to highly potent 1,2,3-triazole based infectivity inhibitors (EC50 ≤ 20 nM).

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:umu:diva-142974 (URN)10.1021/acs.jmedchem.7b00716 (DOI)000416500200019 ()29053275 (PubMedID)
Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2018-08-28Bibliographically approved
Good, J. A. D., Silver, J., Nunez-Otero, C., Bahnan, W., Krishnan, K. S., Salin, O., . . . Almqvist, F. (2016). Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity. Journal of Medicinal Chemistry, 59(5), 2094-2108
Open this publication in new window or tab >>Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity
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2016 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 59, no 5, p. 2094-2108Article in journal (Refereed) Published
Abstract [en]

The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 <= 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 mu M. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Microbiology in the medical area Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-119066 (URN)10.1021/acs.jmedchem.5b01759 (DOI)000372043400031 ()26849778 (PubMedID)
Available from: 2016-04-20 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
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