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Sjöström, EvaORCID iD iconorcid.org/0009-0001-3629-611X
Publications (7 of 7) Show all publications
Durcik, M., Glinghammar, B., Sjöström, E., Bohlin, M., Oreskär, J., Alvér, S. & Peterlin Mašič, L. (2023). New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus. Journal of Medicinal Chemistry, 66(6), 3968-3994
Open this publication in new window or tab >>New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus
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2023 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 66, no 6, p. 3968-3994Article in journal (Refereed) Published
Abstract [en]

A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125-0.25 μg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1-4 μg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated. © 2023 The Authors. 
Place, publisher, year, edition, pages
American Chemical Society, 2023
Keywords
antiinfective agent, DNA topoisomerase (ATP hydrolysing), DNA topoisomerase IV, animal, chemistry, metabolism, microbial sensitivity test, mouse, Staphylococcus aureus, Animals, Anti-Bacterial Agents, DNA Gyrase, Mice, Microbial Sensitivity Tests, Vancomycin-Resistant Staphylococcus aureus
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:ri:diva-64323 (URN)10.1021/acs.jmedchem.2c01905 (DOI)2-s2.0-85149718595 (Scopus ID)
Note

Funding details: 2022-2.1.1-NL-2022-00008, NKFIH-871-3/2020; Funding details: Wellcome Trust, WT, 110072/Z/15/Z, BB/P012523/1; Funding details: European Federation of Pharmaceutical Industries and Associations, EFPIA; Funding details: Biotechnology and Biological Sciences Research Council, BBSRC, BB/J014524/1; Funding details: European Research Council, ERC, H2020-ERC-2014-CoG 648364; Funding details: Javna Agencija za Raziskovalno Dejavnost RS, ARRS, BI-HU/19-20-008, J1-3030, J1-3031, P1-0208; Funding details: Seventh Framework Programme, FP7, FP7/2007–2013; Funding details: Innovative Medicines Initiative, IMI, 115583; Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, KKP 126506; Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA; Funding text 1: The study was funded by the Slovenian Research Agency (grant no. P1-0208, J1-3030, J1-3031, and BI-HU/19-20-008). Part of the research presented in this paper was conducted as part of the ND4BB ENABLE Consortium and has received support from the Innovative Medicines Initiative Joint Undertaking under grant no. 115583, resources of which are comprising financial contributions from the European Union’s seventh framework program (FP7/2007–2013) and EFPIA companies’ in-kind contribution. S.R.H. was supported by an iCASE studentship funded by BBSRC and Redx Pharma Plc (BB/J014524/1). Work in A.M. laboratory is supported by an Investigator Award from the Wellcome Trust (110072/Z/15/Z) and by a BBSRC Institute Strategic Programme Grant (BB/P012523/1). We thank Diamond Light Source for access to beamline I04 under proposal MX25108. Work in C.P. laboratory is supported by the following research grants: the National Research Development and Innovation Office “Élvonal” Programme KKP 126506 (C.P.), the ELKH Lendület Programme LP-2017–10/2020 (C.P.), the National Laboratory of Biotechnology Grant NKFIH-871-3/2020 (C.P.), the National Laboratory of Biotechnology Grant 2022-2.1.1-NL-2022-00008 (C.P.), the European Research Council H2020-ERC-2014-CoG 648364- Resistance Evolution (C.P.), the ÚNKP-22-4 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (P.E.S.), the ÚNKP-22-4 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, the Development and Innovation Fund (P.E.S.), the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (M.C.), and the ÚNKP-22-2 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (M.C.). The authors thank Dora Bokor for proofreading the manuscript.; Funding text 2: The study was funded by the Slovenian Research Agency (grant no. P1-0208, J1-3030, J1-3031, and BI-HU/19-20-008). Part of the research presented in this paper was conducted as part of the ND4BB ENABLE Consortium and has received support from the Innovative Medicines Initiative Joint Undertaking under grant no. 115583, resources of which are comprising financial contributions from the European Union’s seventh framework program (FP7/2007-2013) and EFPIA companies’ in-kind contribution. S.R.H. was supported by an iCASE studentship funded by BBSRC and Redx Pharma Plc (BB/J014524/1). Work in A.M. laboratory is supported by an Investigator Award from the Wellcome Trust (110072/Z/15/Z) and by a BBSRC Institute Strategic Programme Grant (BB/P012523/1). We thank Diamond Light Source for access to beamline I04 under proposal MX25108. Work in C.P. laboratory is supported by the following research grants: the National Research Development and Innovation Office “Élvonal” Programme KKP 126506 (C.P.), the ELKH Lendület Programme LP-2017-10/2020 (C.P.), the National Laboratory of Biotechnology Grant NKFIH-871-3/2020 (C.P.), the National Laboratory of Biotechnology Grant 2022-2.1.1-NL-2022-00008 (C.P.), the European Research Council H2020-ERC-2014-CoG 648364- Resistance Evolution (C.P.), the ÚNKP-22-4 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (P.E.S.), the ÚNKP-22-4 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, the Development and Innovation Fund (P.E.S.), the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (M.C.), and the ÚNKP-22-2 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (M.C.). The authors thank Dora Bokor for proofreading the manuscript.

Available from: 2023-05-08 Created: 2023-05-08 Last updated: 2024-05-20Bibliographically approved
Schavkan, A., Gollwitzer, C., Garcia-Diez, R., Krumrey, M., Minelli, C., Bartczak, D., . . . Shard, A. (2019). Number concentration of gold nanoparticles in suspension: SAXS and spICPMS as traceable methods compared to laboratory methods. Nanomaterials, 9(4), Article ID 502.
Open this publication in new window or tab >>Number concentration of gold nanoparticles in suspension: SAXS and spICPMS as traceable methods compared to laboratory methods
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2019 (English)In: Nanomaterials, E-ISSN 2079-4991, Vol. 9, no 4, article id 502Article in journal (Refereed) Published
Abstract [en]

The industrial exploitation of high value nanoparticles is in need of robust measurement methods to increase the control over product manufacturing and to implement quality assurance. InNanoPart, a European metrology project responded to these needs by developing methods for the measurement of particle size, concentration, agglomeration, surface chemistry and shell thickness. This paper illustrates the advancements this project produced for the traceable measurement of nanoparticle number concentration in liquids through small angle X-ray scattering (SAXS) and single particle inductively coupled plasma mass spectrometry (spICPMS). It also details the validation of a range of laboratory methods, including particle tracking analysis (PTA), dynamic light scattering (DLS), differential centrifugal sedimentation (DCS), ultraviolet visible spectroscopy (UV-vis) and electrospray-differential mobility analysis with a condensation particle counter (ES-DMA-CPC). We used a set of spherical gold nanoparticles with nominal diameters between 10 nm and 100 nm and discuss the results from the various techniques along with the associated uncertainty budgets.
Place, publisher, year, edition, pages
MDPI AG, 2019
Keywords
Comparison, Laboratory methods, Nanoparticles, Number concentration, Suspensions, Traceability
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-38900 (URN)10.3390/nano9040502 (DOI)2-s2.0-85065464814 (Scopus ID)
Note

; Funding details: Singapore Eye Research Institute, 15.0205; Funding details: Department for Business, Energy and Industrial Strategy; Funding details: National Institute of Standards and Technology; Funding text 1: Funding: This work was funded by the 14IND12 InNanoPart project of the EMPIR programme co-financed by the EMPIR Participating States and by the European Union’s Horizon 2020 research and innovation programme, as well as the National Measurement System of the UK Department for Business, Energy and Industrial Strategy (BEIS). METAS gratefully acknowledges funding from the Swiss State Secretariat for Education, Research and lnnovation (SERI) under contract number 15.0205.; Funding text 2: Analysis of variance UK Department for Bussiness, Energy and Industrial Strategy Berliner Elektronenspeicherring für Synchrotronstrahlung Differential Centrifugal Sedimentation Dansk Fundamental Metrologi Dienst Landbouwkundig Onderzoek Dynamic light scattering Electron multiplying charge coupled device European Metrology Programme for Innovation and Research Electrospray-differential mobility analysis with a condensation particle counter Four-crystal monochromator Raman spectroscopy with hollow fiber Helmholtz–Zentrum Berlin für Materialien und Energie GmbH Light emitting diode Laboratory of government chemist Federal Institute of Metrology of Switzerland Mass flow meter National Institute of Standards and Technology National Physical Laboratory Polystyrene Particle tracking analysis Physikalisch-Technische Bundesanstalt Polyvinyl alcohol Research Institutes of Sweden Small-angle X-ray scattering Swiss State Secretariat for Education, Research and Innovation Systeme International Single particle inductively coupled plasma mass spectroscopy Transmission electron microscopy Transient analysis Ultra-violet visible spectroscopy

Available from: 2019-06-03 Created: 2019-06-03 Last updated: 2024-04-08Bibliographically approved
Minelli, C., Bartczak, D., Peters, R., Rissler, J., Undas, A., Sikora, A., . . . Shard, A. G. (2019). Sticky Measurement Problem: Number Concentration of Agglomerated Nanoparticles. Langmuir, 35(14), 4927-4935
Open this publication in new window or tab >>Sticky Measurement Problem: Number Concentration of Agglomerated Nanoparticles
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2019 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 35, no 14, p. 4927-4935Article in journal (Refereed) Published
Abstract [en]

Measuring the number concentration of colloidal nanoparticles (NPs) is critical for assessing reproducibility, enabling compliance with regulation, and performing risk assessments of NP-enabled products. For nanomedicines, their number concentration directly relates to their dose. However, the lack of relevant reference materials and established traceable measurement approaches make the validation of methods for NP number concentration difficult. Furthermore, commercial products often exhibit agglomeration, but guidelines for dealing with nonideal samples are scarce. We have compared the performance of five benchtop measurement methods for the measurement of colloidal number concentration in the presence of different levels of agglomeration. The methods are UV-visible spectroscopy, differential centrifugal sedimentation, dynamic light scattering, particle tracking analysis, and single-particle inductively coupled plasma mass spectrometry. We find that both ensemble and particle-by-particle methods are in close agreement for monodisperse NP samples and three methods are within 20% agreement for agglomerated samples. We discuss the sources of measurement uncertainties, including how particle agglomeration affects measurement results. This work is a first step toward validation and expansion of the toolbox of methods available for the measurement of real-world NP products.
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-38275 (URN)10.1021/acs.langmuir.8b04209 (DOI)30869903 (PubMedID)2-s2.0-85064223022 (Scopus ID)
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2024-04-08Bibliographically approved
Moen, I., Ugland, H., Strömberg, N., Sjöström, E., Karlsson, A., Ringstad, L., . . . Hagleröd, C. (2018). Development of a novel in situ gelling skin dressing: Deliveringhigh levels of dissolved oxygen at pH 5.5. Health Sci Rep., Article ID e57.
Open this publication in new window or tab >>Development of a novel in situ gelling skin dressing: Deliveringhigh levels of dissolved oxygen at pH 5.5
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2018 (English)In: Health Sci Rep., article id e57Article in journal (Refereed) Published
Abstract [en]

Background and aims: Wound healing requires appropriate oxygen and pH levels.Oxygen therapy and pH‐modulating treatments have shown positive effects onwound healing. Thus, a dressing, which combines high levels of dissolved oxygen(DO) with the pH of intact skin, may improve wound healing. Our aims were to (1) formulatean in situ gelling dressing with high levels of DO and with the pH level of intactskin, (2) evaluate physical and chemical properties of the dressing, and (3) elucidatebasic effects of elevated levels of DO on human skin cells in vitro.Methods: A dressing was formulated with 15 to 16 wt% poloxamer 407, acetatebuffer, and oxygenated water. Stability of pH and DO, rheology, and shelf life wereanalysed. Furthermore, in vitro studies of the effect of increased levels of DO wereperformed.Results: An in situ gelling wound dressing, with a DO concentration rangingbetween 25 and 35 mg/L and a pH of 5.5, was formulated. The DO concentrationwas stable above 22 mg/L for at least 30 hours when applied on a surface at 35°Cand covered for directed diffusion into the intended wound area. At storage, thedressing had stable pH for 3 months and stable DO concentration over 30 mg/L for7 weeks. Increasing DO significantly enhanced intracellular ATP in human skin cells,without changing reactive oxygen species production, proliferation rate, or viability.Conclusion: The developed dressing may facilitate wound healing by deliveringcontrolled and stable oxygen levels, providing adjustable pH for optimized healing,and increasing intracellular ATP availability.
Keywords
hyperoxia, intracellular ATP, thermo sensitive, topical dressing, wound healing
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-34880 (URN)10.1002/hsr2.57 (DOI)
Note

Eurostars project, Grant/Award Number: E!10397

Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2024-04-08
Sjöström, E. (2013). Cyclic strain controlled testing of Steel 10 in MODFLAT (ed.). Swerea KIMAB AB
Open this publication in new window or tab >>Cyclic strain controlled testing of Steel 10 in MODFLAT
2013 (English)Report (Refereed)
Abstract [en]

This is a part report in the Swerea KIMAB AB project 222009 Modflat aiming to verify and develop material models describing the plastic response from cyclic strain testing. The experimental result presented in this report is used to interpret the material response by using material model (Chaboche-Lemaître) and simulation tools.
Place, publisher, year, edition, pages
Swerea KIMAB AB, 2013
Series
Rapport / Institutet för metallforskning, ISSN 1403-848X ; KIMAB-2013-108
National Category
Materials Engineering
Identifiers
urn:nbn:se:ri:diva-13010 (URN)
Available from: 2016-09-22 Created: 2016-09-22 Last updated: 2024-04-08Bibliographically approved
Sjöström, E. (2013). Cyclic strain controlled testingof Stainless steel 1in MODFLAT (ed.). Swerea KIMAB AB
Open this publication in new window or tab >>Cyclic strain controlled testingof Stainless steel 1in MODFLAT
2013 (English)Report (Refereed)
Abstract [en]

This is a part report in the Swerea KIMAB AB project 222009 Modflat aiming to verify and develop material models describing the plastic response from cyclic strain testing. The experimental result presented in this report is used to describe the material response by using a material model (Chaboche-Lemaître) and simulation tools.
Place, publisher, year, edition, pages
Swerea KIMAB AB, 2013
Series
Rapport / Institutet för metallforskning, ISSN 1403-848X ; KIMAB-2013-106
National Category
Materials Engineering
Identifiers
urn:nbn:se:ri:diva-13011 (URN)
Available from: 2016-09-22 Created: 2016-09-22 Last updated: 2024-04-08Bibliographically approved
Sjöström, E. (2013). Reversed cyclic strain controlled testing of Steel 1 in MODFLAT (ed.). Swerea KIMAB AB
Open this publication in new window or tab >>Reversed cyclic strain controlled testing of Steel 1 in MODFLAT
2013 (English)Report (Refereed)
Abstract [en]

This is a part report in the Swerea KIMAB AB project 222009 Modflat aiming to verify and develop material models describing the plastic response from cyclic strain testing. The experimental result presented in this report is used to interpret the material response by using material model (Chaboche-Lemaître) and simulation tools.
Place, publisher, year, edition, pages
Swerea KIMAB AB, 2013
Series
Rapport / Institutet för metallforskning, ISSN 1403-848X ; KIMAB-2013-107
National Category
Materials Engineering
Identifiers
urn:nbn:se:ri:diva-13012 (URN)
Available from: 2016-09-22 Created: 2016-09-22 Last updated: 2024-04-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0009-0001-3629-611X

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