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Potter, R., Ayala, M. & Tilevik, A. (2024). Identification of biomarker candidates for exfoliative glaucoma from autoimmunity profiling. BMC Ophthalmology, 24(1), Article ID 44.
Open this publication in new window or tab >>Identification of biomarker candidates for exfoliative glaucoma from autoimmunity profiling
2024 (English)In: BMC Ophthalmology, E-ISSN 1471-2415, Vol. 24, no 1, article id 44Article in journal (Refereed) Published
Abstract [en]

Background: Exfoliative glaucoma (XFG) is a subtype of open-angle glaucoma characterized by distinctive extracellular fibrils and a yet unknown pathogenesis potentially involving immune-related factors. The aim of this exploratory study was to identify biomarkers for XFG using data from autoimmunity profiling performed on blood samples from a Scandinavian cohort of patients. Methods: Autoantibody screening was analyzed against 258 different protein fragments in blood samples taken from 30 patients diagnosed with XFG and 30 healthy donors. The 258 protein fragments were selected based on a preliminary study performed on 3072 randomly selected antigens and antigens associated with the eye. The “limma” package was used to perform moderated t-tests on the proteomic data to identify differentially expressed reactivity between the groups. Results: Multiple associated genes were highlighted as possible biomarker candidates including FUT2, CDH5, and the LOX family genes. Using seven variables, our binary logistic regression model was able to classify the cases from the controls with an AUC of 0.85, and our reduced model using only one variable corresponding to the FUT2 gene provided an AUC of 0.75, based on LOOCV. Furthermore, over-representation gene analysis was performed to identify pathways that were associated with antigens differentially bound to self-antibodies. This highlighted the enrichment of pathways related to collagen fibril formation and the regulatory molecules mir-3176 and mir-876-5p. Conclusions: This study suggests several potential biomarkers that may be useful in developing further models of the pathology of XFG. In particular, CDH5, FUT2, and the LOX family seem to have a relationship which merits additional exploration. 

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Autoimmunity, Biomarkers, Exfoliation, Genes, Glaucoma
National Category
Ophthalmology Medical Genetics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Bioinformatics and Systems Biology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-23583 (URN)10.1186/s12886-024-03314-y (DOI)001153831500002 ()38287276 (PubMedID)2-s2.0-85183441039 (Scopus ID)
Funder
University of Gothenburg
Note

CC BY 4.0 DEED

© 2024, The Author(s).

Correspondence Address: R. Potter; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; email: ryan.potter@his.se

Open access funding provided by University of Gothenburg. This study was funded by Synskadades Vänner Skaraborg (SVS).

Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2024-04-15Bibliographically approved
Shemirani, M. I., Tilevik, D., Tilevik, A., Jurcevic, S., Arnellos, D., Enroth, H. & Pernestig, A.-K. (2023). Benchmarking of two bioinformatic workflows for the analysis of whole-genome sequenced Staphylococcus aureus collected from patients with suspected sepsis. BMC Infectious Diseases, 23(1), 39, Article ID 39.
Open this publication in new window or tab >>Benchmarking of two bioinformatic workflows for the analysis of whole-genome sequenced Staphylococcus aureus collected from patients with suspected sepsis
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2023 (English)In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 23, no 1, p. 39-, article id 39Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The rapidly growing area of sequencing technologies, and more specifically bacterial whole-genome sequencing, could offer applications in clinical microbiology, including species identification of bacteria, prediction of genetic antibiotic susceptibility and virulence genes simultaneously. To accomplish the aforementioned points, the commercial cloud-based platform, 1928 platform (1928 Diagnostics, Gothenburg, Sweden) was benchmarked against an in-house developed bioinformatic pipeline as well as to reference methods in the clinical laboratory.

METHODS: Whole-genome sequencing data retrieved from 264 Staphylococcus aureus isolates using the Illumina HiSeq X next-generation sequencing technology was used. The S. aureus isolates were collected during a prospective observational study of community-onset severe sepsis and septic shock in adults at Skaraborg Hospital, in the western region of Sweden. The collected isolates were characterized according to accredited laboratory methods i.e., species identification by MALDI-TOF MS analysis and phenotypic antibiotic susceptibility testing (AST) by following the EUCAST guidelines. Concordance between laboratory methods and bioinformatic tools, as well as concordance between the bioinformatic tools was assessed by calculating the percent of agreement.

RESULTS: There was an overall high agreement between predicted genotypic AST and phenotypic AST results, 98.0% (989/1006, 95% CI 97.3-99.0). Nevertheless, the 1928 platform delivered predicted genotypic AST results with lower very major error rates but somewhat higher major error rates compared to the in-house pipeline. There were differences in processing times i.e., minutes versus hours, where the 1928 platform delivered the results faster. Furthermore, the bioinformatic workflows showed overall 99.4% (1267/1275, 95% CI 98.7-99.7) agreement in genetic prediction of the virulence gene characteristics and overall 97.9% (231/236, 95% CI 95.0-99.2%) agreement in predicting the sequence types (ST) of the S. aureus isolates.

CONCLUSIONS: Altogether, the benchmarking disclosed that both bioinformatic workflows are able to deliver results with high accuracy aiding diagnostics of severe infections caused by S. aureus. It also illustrates the need of international agreement on quality control and metrics to facilitate standardization of analytical approaches for whole-genome sequencing based predictions.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Antimicrobial susceptibility, Benchmarking, Clinical microbiology, Illumina sequencing, S. aureus, Species identification, Virulence genes, Whole-genome sequencing
National Category
Microbiology Bioinformatics and Systems Biology Infectious Medicine Microbiology in the medical area Genetics
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-22199 (URN)10.1186/s12879-022-07977-0 (DOI)000921125300004 ()36670352 (PubMedID)2-s2.0-85146795212 (Scopus ID)
Funder
Knowledge Foundation, 206/0330Knowledge Foundation, 2017/14
Note

CC BY 4.0

The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Correspondence: Anna‑Karin Pernestig anna‑karin.pernestig@his.se

Open access funding provided by University of Skövde. Swedish Knowledge Foundation BioMine Grant No. 206/0330, Swedish Knowledge Foundation Associate Senior Lecturer in Systems biology, Grant No. 2017/14, Stiftelsen Tornspiran, Internal research fund, Unilabs AB.

The datasets generated and/or analysed during the current study are available in the online NCBI repository, https://www.ncbi.nlm.nih.gov/, BioProject PRJNA606666, http://www.ncbi.nlm.nih.gov/bioproject/606666

Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2024-01-17Bibliographically approved
Friman, V., Quinti, I., Davydov, A. N., Shugay, M., Farroni, C., Engström, E., . . . Grimsholm, O. (2023). Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations. Cell Reports, 42(5), Article ID 112446.
Open this publication in new window or tab >>Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations
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2023 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 42, no 5, article id 112446Article in journal (Refereed) Published
Abstract [en]

Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity. 

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
CD27<sup>bright</sup> memory B cells, common variable immunodeficiency, CP: Immunology, immunoglobulin sequencing, naive B cells, peripheral B cell selection, receptor editing, transcriptomic analysis
National Category
Immunology in the medical area Immunology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-22484 (URN)10.1016/j.celrep.2023.112446 (DOI)000996158800001 ()37119135 (PubMedID)2-s2.0-85153595326 (Scopus ID)
Funder
EU, Horizon 2020, 754412Wilhelm och Martina Lundgrens Vetenskapsfond, 2018-2300, 2019-2986, 2020-3395Swedish Society of Medicine, SLS-593371Gunvor och Josef Anérs stiftelse, FB19-0054O.E. och Edla Johanssons vetenskapliga stiftelseStiftelsen Sigurd och Elsa Goljes minneStiftelsen Sigurd och Elsa Goljes minneStiftelsen Apotekare Hedbergs Fund for Medical ResearchRegion Västra Götaland
Note

CC BY 4.0

© 2023 The Author(s)

Correspondence ola.grimsholm@meduniwien.ac.at

This work has received funding from the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie grant agreement 754412 (to O.G.). O.G. was also supported by a personal fellowship from EFIS as well as research grants from the Wilhelm and Martina Lundgren Foundation (grants 2018-2300, 2019-2986, and 2020-3395), the Axel Linder Foundation, the Swedish Medical Society (grant SLS-593371), the Gunvor and Josef Anér Foundation (grant FB19-0054), the O.E. and Edla Johansson Science Foundation, the Elsa and Sigurd Memorial Foundation, the Pharmacist Hedberg Foundation for Medical Research, The Royal Society of Arts and Sciences in Gothenburg (grants 2018-184, 2020-422, and 2021-548), the Tore Nilsson Foundation (grants 2015-00218, 2018-00648, and 2020-00789), and The Healthcare Committee, Region Västra Götaland. This work was also supported by The Health & Medical Care Committee of the Region Västra Götaland and by grants from the Swedish state under an agreement between the Swedish government and the country councils, the ALF agreement (73740) (to V.F.). The work of S.P.A. was supported by a grant from the Austrian Science Fund (FWF, project P32953). The work was also supported by the Italian Ministry of Health (grant RF2013-02358960) (to R.C.). A.N.D. was supported by the Ministry of Education, Youth and Sports of the Czech Republic (project CEITEC 2020 LQ1601). M.S. and D.M.C. were supported by the Ministry of Science and Higher Education of the Russian Federation (project 075-15-2019-1789). None of the funding sources had any involvement in the study design. We thank Dr. Mattias Svensson for critical input to the manuscript. We are also thankful to Dr. Vincent Collins for help with language editing of the manuscript.

Available from: 2023-05-04 Created: 2023-05-04 Last updated: 2024-01-17Bibliographically approved
Sundell, T., Grimstad, K., Camponeschi, A., Tilevik, A., Gjertsson, I. & Mårtensson, I.-L. (2023). Single-cell RNA sequencing analyses: interference by the genes that encode the B-cell and T-cell receptors. Briefings in Functional Genomics & Proteomics, 22(3), 263-273, Article ID elac044.
Open this publication in new window or tab >>Single-cell RNA sequencing analyses: interference by the genes that encode the B-cell and T-cell receptors
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2023 (English)In: Briefings in Functional Genomics & Proteomics, ISSN 2041-2649, E-ISSN 2041-2657, Vol. 22, no 3, p. 263-273, article id elac044Article in journal (Refereed) Published
Abstract [en]

B and T cells are integral parts of the immune system and are implicated in many diseases, e.g. autoimmunity. Towards understanding the biology of B and T cells and subsets thereof, their transcriptomes can be analyzed using single-cell RNA sequencing. In some studies, the V(D)J transcripts encoding the variable regions of the B- and T-cell antigen receptors have been removed before the analyses. However, a systematic analysis of the effects of including versus excluding these genes is currently lacking. We have investigated the effects of these transcripts on unsupervised clustering and down-stream analyses of single-cell RNA sequencing data from B and T cells. We found that exclusion of the B-/T-cell receptor genes prior to unsupervised clustering resulted in clusters that represented biologically meaningful subsets, such as subsets of memory B and memory T cells. Furthermore, pseudo-time and trajectory inference analyses of early B-lineage cells resulted in a developmental pathway from progenitor to immature B cells. In contrast, when the B-/T-cell receptor genes were not removed, with the PCs used for clustering consisting of up to 70% V-genes, this resulted in some clusters being defined exclusively by V-gene segments. These did not represent biologically meaningful subsets; for instance in the early B-lineage cells, these clusters contained cells representing all developmental stages. Thus, in studies of B and T cells, to derive biologically meaningful results, it is imperative to remove the gene sequences that encode B- and T-cell receptors.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
BCR-genes, TCR-genes, immunoglobulins, interference, scRNA-seq, single-cell RNA sequencing
National Category
Cell and Molecular Biology Rheumatology and Autoimmunity Immunology in the medical area
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-22155 (URN)10.1093/bfgp/elac044 (DOI)000893680100001 ()36473726 (PubMedID)2-s2.0-85166264658 (Scopus ID)
Funder
Swedish Research Council, 2018-03128Swedish Research Council, 2021-01150Swedish Research Council, 2016-01576Swedish Cancer Society, 19 0464Swedish Childhood Cancer Foundation, PR2018-0170Swedish Childhood Cancer Foundation, PR2020-0147Swedish Childhood Cancer Foundation, TJ2019-0098Swedish Rheumatism Association, R-94129Swedish Rheumatism Association, R-940945Adlerbertska Research FoundationIngaBritt and Arne Lundberg’s Research Foundation
Note

CC BY-NC 4.0

Corresponding author: Inga-Lill Mårtensson, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Tel.:+46(0)703640068; E-mail: lill.martensson@rheuma.gu.se

This work was supported by the Swedish Research Council, grants 2018-03128 and 2021-01150 (ILM) and 2016-01576 (IG); the Swedish Cancer Foundation, grant 19 0464 (ILM); the Swedish Childhood Cancer Fund, grants PR2018-0170 and PR2020-0147 (ILM), and TJ2019-0098 (AC); Assar Gabrielsson’s Foundation, FB21-104 (AC); Patient Association for Rheumatic Diseases, R-94129 (ILM) and R-940945 (IG); ALF (agreement between the Government of Sweden and the County Councils), ALFGBG-719631 (IG); Adlerbertska stiftelsen (TS); and the IngaBritt och Arne Lundbergs Foundation (ILM, IG)

Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2023-12-15Bibliographically approved
Olesen, K., Moruzzi, N., Bulatovic, I., Folmes, C., Jeon, R., Felldin, U., . . . Grinnemo, K.-H. (2022). Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells. Metabolism Open, 13(March), Article ID 100167.
Open this publication in new window or tab >>Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells
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2022 (English)In: Metabolism Open, E-ISSN 2589-9368, Vol. 13, no March, article id 100167Article in journal (Refereed) Published
Abstract [en]

Objective

Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion.

Materials and methods

We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems.

Results

Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found.

Conclusions

In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Mesenchymal stromal cells, Development, Aerobic glycolysis, Hypoxia, Mitochondria, Metabolism
National Category
Cell and Molecular Biology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-20898 (URN)10.1016/j.metop.2022.100167 (DOI)35528374 (PubMedID)
Funder
Swedish Research Council, 2013–3590Region StockholmFamiljen Erling-Perssons StiftelseEU, European Research Council, ERC-2018-AdG (834860 EYELETS)Region Uppsala
Note

CC BY-NC-ND 4.0

Corresponding author: Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. E-mail address: karl-henrik.grinnemo@surgsci.uu.se (K.-H. Grinnemo).

Available online 3 February 2022, Version of Record 5 February 2022

The project was funded by Karolinska Institute-Mayo Clinic Collaborative Grant 2013; The Swedish Research Council young investigator: 2013–3590; Stockholm county; The Swedish Research Council; The Family Erling-Persson Foundation; ERC-2018-AdG (834860 EYELETS); Uppsala county; Uppsala County Association against Heart and Lung Diseases; and Higher Education of the Russian Federation (agreement no. 075-15-2020-899).

Available from: 2022-02-04 Created: 2022-02-04 Last updated: 2023-06-22Bibliographically approved
Tilevik, D., Pernestig, A.-K., Fagerlind, M., Tilevik, A., Ljungström, L., Johansson, M. & Enroth, H. (2022). Sequence-based genotyping of extra-intestinal pathogenic Escherichia coli isolates from patients with suspected community-onset sepsis, Sweden. Microbial Pathogenesis, 173(Part A), Article ID 105836.
Open this publication in new window or tab >>Sequence-based genotyping of extra-intestinal pathogenic Escherichia coli isolates from patients with suspected community-onset sepsis, Sweden
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2022 (English)In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 173, no Part A, article id 105836Article in journal (Refereed) Published
Abstract [en]

Extra-intestinal pathogenic Escherichia coli (ExPEC) strains are responsible for a large number of human infections globally. The management of infections caused by ExPEC has been complicated by the emergence of antimicrobial resistance, most importantly the increasing recognition of isolates producing extended-spectrum β-lactamases (ESBL). Herein, we used whole-genome sequencing (WGS) on ExPEC isolates for a comprehensive genotypic characterization. Twenty-one ExPEC isolates, nine with and 12 without ESBL-production, from 16 patients with suspected sepsis were sequenced on an Illumina MiSeq platform. Analysis of WGS data was performed with widely used bioinformatics software and tools for genotypic characterization of the isolates. A higher number of plasmids, virulence and resistance genes were observed in the ESBL-producing isolates than the non-ESBL-producing, although not statistically significant due to the low sample size. All nine ESBL-producing ExPEC isolates presented with at least one bla gene, as did three of the 12 without ESBL-production. Multi-locus sequence typing analysis revealed a diversity of sequence types whereas phylogroup A prevailed among isolates both with and without ESBL-production. In conclusion, this limited study shows that analysis of WGS data can be used for genotypic characterization of ExPEC isolates to obtain in-depth information of clinical relevance.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Escherichia coli isolates, Whole-genome sequencing, ESBL, Virulence, Plasmid, Resistance genes, Phylogenetic groups
National Category
Microbiology in the medical area Microbiology Infectious Medicine Genetics Medical Genetics Bioinformatics and Systems Biology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-21968 (URN)10.1016/j.micpath.2022.105836 (DOI)000891651100007 ()36265734 (PubMedID)2-s2.0-85140323332 (Scopus ID)
Note

CC BY 4.0

Available online 17 October 2022

Corresponding author: Diana Tilevik

This research received no external financial support.

Available from: 2022-10-18 Created: 2022-10-18 Last updated: 2023-01-17Bibliographically approved
Saxenborn, P., Baxter, J., Tilevik, A., Fagerlind, M., Dyrkell, F., Pernestig, A.-K., . . . Tilevik, D. (2021). Genotypic Characterization of Clinical Klebsiella spp. Isolates Collected From Patients With Suspected Community-Onset Sepsis, Sweden. Frontiers in Microbiology, 12, Article ID 640408.
Open this publication in new window or tab >>Genotypic Characterization of Clinical Klebsiella spp. Isolates Collected From Patients With Suspected Community-Onset Sepsis, Sweden
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2021 (English)In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 12, article id 640408Article in journal (Refereed) Published
Abstract [en]

Klebsiella is a genus of Gram-negative bacteria known to be opportunistic pathogens that may cause a variety of infections in humans. Highly drug-resistant Klebsiella species, especially K. pneumoniae, have emerged rapidly and are becoming a major concern in clinical management. Although K. pneumoniae is considered the most important pathogen within the genus, the true clinical significance of the other species is likely underrecognized due to the inability of conventional microbiological methods to distinguish between the species leading to high rates of misidentification. Bacterial whole-genome sequencing (WGS) enables precise species identification and characterization that other technologies do not allow. Herein, we have characterized the diversity and traits of Klebsiella spp. in community-onset infections by WGS of clinical isolates (n = 105) collected during a prospective sepsis study in Sweden. The sequencing revealed that 32 of the 82 isolates (39.0%) initially identified as K. pneumoniae with routine microbiological methods based on cultures followed by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS) had been misidentified. Of these, 23 were identified as Klebsiella variicola and nine as other members of the K. pneumoniae complex. Comparisons of the number of resistance genes showed that significantly fewer resistance genes were detected in Klebsiella oxytoca compared to K. pneumoniae and K. variicola (both values of p < 0.001). Moreover, a high proportion of the isolates within the K. pneumoniae complex were predicted to be genotypically multidrug-resistant (MDR; 79/84, 94.0%) in contrast to K. oxytoca (3/16, 18.8%) and Klebsiella michiganensis (0/4, 0.0%). All isolates predicted as genotypically MDR were found to harbor the combination of β-lactam, fosfomycin, and quinolone resistance markers. Multi-locus sequence typing (MLST) revealed a high diversity of sequence types among the Klebsiella spp. with ST14 (10.0%) and ST5429 (10.0%) as the most prevalent ones for K. pneumoniae, ST146 for K. variicola (12.0%), and ST176 for K. oxytoca (25.0%). In conclusion, the results from this study highlight the importance of using high-resolution genotypic methods for identification and characterization of clinical Klebsiella spp. isolates. Our findings indicate that infections caused by other members of the K. pneumoniae complex than K. pneumoniae are a more common clinical problem than previously described, mainly due to high rates of misidentifications.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
Klebsiella, whole-genome sequencing, antimicrobial susceptibility, clinical microbiology, multidrug resistance, nanopore-based sequencing, Illumina sequencing
National Category
Medical and Health Sciences Microbiology in the medical area
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-19688 (URN)10.3389/fmicb.2021.640408 (DOI)000650016100001 ()33995300 (PubMedID)2-s2.0-85105914228 (Scopus ID)
Funder
Knowledge Foundation, 206/0330
Note

CC BY 4.0

Correspondence: Diana Tilevik diana.tilevik@his.se

Available from: 2021-05-06 Created: 2021-05-06 Last updated: 2024-01-17Bibliographically approved
Olesen, K., Rodin, S., Mak, W. C., Felldin, U., Österholm, C., Tilevik, A. & Grinnemo, K.-H. (2021). Spatiotemporal extracellular matrix modeling for in situ cell niche studies. Stem Cells, 39(12), 1751-1765
Open this publication in new window or tab >>Spatiotemporal extracellular matrix modeling for in situ cell niche studies
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2021 (English)In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 39, no 12, p. 1751-1765Article in journal (Refereed) Published
Abstract [en]

Extracellular matrix (ECM) components govern a range of cell functions such as migration, proliferation, maintenance of stemness and differentiation. Cell niches that harbor stem-/progenitor cells, with matching ECM, have been shown in a range of organs, although their presence in the heart is still under debate. Determining niches depends on a range of in vitro and in vivo models and techniques, where animal models are powerful tools for studying cell-ECM dynamics, however, they are costly and time-consuming to use. In vitro models based on recombinant ECM proteins lack the complexity of the in vivo ECM. To address these issues, we present the Spatiotemporal Extracellular Matrix Model (StEMM) for studies of cell-ECM dynamics, such as cell niches. This model combines gentle decellularization and sectioning of cardiac tissue, allowing retention of a complex ECM, with recellularization and subsequent image processing using image stitching, segmentation, automatic binning and generation of cluster maps. We have thereby developed an in situ representation of the cardiac ECM that is useful for assessment of repopulation dynamics and to study the effect of local ECM composition on phenotype preservation of reseeded mesenchymal progenitor cells. This model provides a platform for studies of organ-specific cell-ECM dynamics and identification of potential cell niches. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Stem cells reside in adult organs within specific microenvironments called cell niches. The heart is a complex organ and so far, the presence and localization of stem-/progenitor cell niches are subject to constant debate. To address these issues, the authors have developed the Spatiotemporal Extracellular Matrix Model (StEMM), which combines a modified protocol for decellularization, with cryo-sectioning, recellularization, and subsequent image processing including automatic binning and generation of cluster maps. StEMM was developed within a cardiac context and validated using syngeneic mesenchymal progenitor cells. However, this model is not restricted with regard to species or organs.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
cardiac, mesenchymal stem cells, multipotential differentiation, pericytes, progenitor cells, scaffold attachment region, stem cell-microenvironment interactions, technology
National Category
Cell and Molecular Biology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-20517 (URN)10.1002/stem.3448 (DOI)000691415300001 ()34418223 (PubMedID)2-s2.0-85113941516 (Scopus ID)
Funder
Region UppsalaSwedish Research Council, 2013-03590
Note

CC BY-NC 4.0

Correspondence: Karl-Henrik Grinnemo, MD, Department of Surgical Sciences, Division of Cardiothoracic Surgery, Uppsala University Hospital, SE-75185 Uppsala, Sweden. Email: karl-henrik.grinnemo@surgsci.uu.se

Funding information: Uppsala Region (RuFu); Uppsala County Council (ALF); Swedish Research Council, Young Investigator, Grant/Award Number: 2013-03590

Available from: 2021-08-31 Created: 2021-08-31 Last updated: 2021-12-21Bibliographically approved
Kokkonen, A., Tilevik, D., Pernestig, A.-K., Tilevik, A., Fagerlind, M. & Enroth, H. (2019). Clinical use of 16SrRNA Ion TorrentNext-generation sequencing and bioinformatics pipeline. In: : . Paper presented at 14th Annual Workshop in Systems Biology, University of Skövde, Sweden, 21 November 2019.
Open this publication in new window or tab >>Clinical use of 16SrRNA Ion TorrentNext-generation sequencing and bioinformatics pipeline
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2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Medical and Health Sciences Infectious Medicine
Research subject
INF502 Biomarkers; Infection Biology
Identifiers
urn:nbn:se:his:diva-18275 (URN)
Conference
14th Annual Workshop in Systems Biology, University of Skövde, Sweden, 21 November 2019
Projects
BioMine
Funder
Knowledge Foundation
Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2021-08-31Bibliographically approved
Irani Shemirani, M., Tilevik, A., Tilevik, D., Pernestig, A.-K. & Enroth, H. (2019). Comparison of Whole Genome Sequencing Pipelines for Analysis of Staphylococcus aureus Isolates from Sepsis Patients. In: : . Paper presented at 14th Annual Workshop in Systems Biology, University of Skövde, Sweden, 21 November 2019.
Open this publication in new window or tab >>Comparison of Whole Genome Sequencing Pipelines for Analysis of Staphylococcus aureus Isolates from Sepsis Patients
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2019 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Medical and Health Sciences Infectious Medicine
Research subject
INF502 Biomarkers; Infection Biology
Identifiers
urn:nbn:se:his:diva-18274 (URN)
Conference
14th Annual Workshop in Systems Biology, University of Skövde, Sweden, 21 November 2019
Projects
BioMine - Data-mining för identifiering, selektion och validering av biomarkörer
Funder
Knowledge Foundation, 20160330
Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2022-12-29Bibliographically approved
Projects
Quantification of kinetic parameters controlling thymocyte development and T cell homeostasis - a systems biology approach in patients and GƒÑi2-/- mice [2009-00312_VR]; University of Skövde
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3747-5950

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