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Article: Comparative Genomics of Clinical Isolates of the Emerging Tick-Borne Pathogen Neoehrlichia mikurensis

Grankvist, Anna / Jaén-Luchoro, Daniel / Wass, Linda / Sikora, Per / Wennerås, Christine

Microorganisms. 2021 July 13, v. 9, no. 7

2021

Abstract: Tick-borne ‘Neoehrlichia (N.) mikurensis’ is the cause of neoehrlichiosis, an infectious vasculitis of humans. This strict intracellular pathogen is a member of the family Anaplasmataceae and has been unculturable until recently. The only available ... ...

Abstract	Tick-borne ‘Neoehrlichia (N.) mikurensis’ is the cause of neoehrlichiosis, an infectious vasculitis of humans. This strict intracellular pathogen is a member of the family Anaplasmataceae and has been unculturable until recently. The only available genetic data on this new pathogen are six partially sequenced housekeeping genes. The aim of this study was to advance the knowledge regarding ‘N. mikurensis’ genomic relatedness with other Anaplasmataceae members, intra-species genotypic variability and potential virulence factors explaining its tropism for vascular endothelium. Here, we present the de novo whole-genome sequences of three ‘N. mikurensis’ strains derived from Swedish patients diagnosed with neoehrlichiosis. The genomes were obtained by extraction of DNA from patient plasma, library preparation using 10× Chromium technology, and sequencing by Illumina Hiseq-4500. ‘N. mikurensis’ was found to have the next smallest genome of the Anaplasmataceae family (1.1 Mbp with 27% GC contents) consisting of 845 protein-coding genes, every third of which with unknown function. Comparative genomic analyses revealed that ‘N. mikurensis’ was more closely related to Ehrlichia chaffeensis than to Ehrlichia ruminantium, the opposite of what 16SrRNA sequence-based phylogenetic analyses determined. The genetic variability of the three whole-genome-sequenced ‘N. mikurensis’ strains was extremely low, between 0.14 and 0.22‰, a variation that was associated with geographic origin. No protein-coding genes exclusively shared by N. mikurensis and E. ruminantium were identified to explain their common tropism for vascular endothelium.
Keywords	DNA ; Ehrlichia chaffeensis ; Ehrlichia ruminantium ; chromium ; endothelium ; genetic variation ; genomics ; pathogens ; patients ; phylogeny ; provenance ; vasculitis ; virulence
Language	English
Dates of publication	2021-0713
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9071488
Database	NAL-Catalogue (AGRICOLA)

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Article: Comparative Genomics of Clinical Isolates of the Emerging Tick-Borne Pathogen

Grankvist, Anna / Jaén-Luchoro, Daniel / Wass, Linda / Sikora, Per / Wennerås, Christine

Microorganisms

2021 Volume 9, Issue 7

Abstract: Tick-borne ' ...

Abstract	Tick-borne '
Language	English
Publishing date	2021-07-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9071488
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Article ; Online: Self-reported symptom severity, general health, and impairment in post-acute phases of COVID-19: retrospective cohort study of Swedish public employees.

Larsson, Simon B / von Feilitzen, Gustaf Stukát / Andersson, Maria E / Sikora, Per / Lindh, Magnus / Nordén, Rickard / Nilsson, Staffan / Sigström, Robert

Scientific reports

2022 Volume 12, Issue 1, Page(s) 19818

Abstract: This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR negative controls. During the first quarter of 2021, we ...

Abstract	This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR negative controls. During the first quarter of 2021, we conducted an online survey among public employees in West Sweden, with a valid COVID-19 test result. The survey assessed past-month severity of 28 symptoms and signs, self-rated health, the WHO Disability Assessment Schedule (WHODAS) 2.0 and illness severity at the time of test. We linked participants' responses to their SARS-CoV-2 PCR tests results. We compared COVID-19 positive and negative participants using univariable and multivariable regression analyses. Out of 56,221 invited, 14,222 (25.3%) responded, with a response rate of 50% among SARS-CoV-2 positive individuals. Analysis included 10,194 participants (86.4% women, mean age 45 years) who tested positive 4-12 weeks (N = 1425; subacute) and > 12 weeks (N = 1584; postcovid) prior to the survey, and 7185 PCR negative participants who did not believe that they had had COVID-19. Symptoms were highly prevalent in all groups, with worst symptoms in subacute phase participants, followed by postcovid phase and PCR negative participants. The most specific symptom for COVID-19 was loss of smell or taste. Both WHODAS 2.0 score and self-rated health were worst in subacute participants, and modestly worse in postcovid participants than in negative controls. Female gender, older age and acute illness severity had larger effects on self-rated health and WHODAS 2.0 score in PCR positive participants than in PCR negative. Studies with longer follow-up are needed to determine the long-term improvement after COVID-19.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Self Report ; Sweden/epidemiology ; COVID-19/epidemiology ; Retrospective Studies ; SARS-CoV-2
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-24307-1
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Article ; Online: Hepatitis E virus genotype 3 strains and a plethora of other viruses detected in raw and still in tap water.

Wang, Hao / Kjellberg, Inger / Sikora, Per / Rydberg, Henrik / Lindh, Magnus / Bergstedt, Olof / Norder, Heléne

Water research

2019 Volume 168, Page(s) 115141

Abstract: In this study, next generation sequencing was used to explore the virome in 20L up to 10,000L water from different purification steps at two Swedish drinking water treatment plants (DWTPs), and in tap water. One DWTP used ultrafiltration (UF) with 20 nm ... ...

Abstract	In this study, next generation sequencing was used to explore the virome in 20L up to 10,000L water from different purification steps at two Swedish drinking water treatment plants (DWTPs), and in tap water. One DWTP used ultrafiltration (UF) with 20 nm pores, the other UV light treatment after conventional treatment of the water. Viruses belonging to 26 different families were detected in raw water, in which 6-9 times more sequence reads were found for phages than for known environmental, plant or vertebrate viruses. The total number of viral reads was reduced more than 4-log10 after UF and 3-log10 over UV treatment. However, for some viruses the reduction was 3.5-log10 after UF, as for hepatitis E virus (HEV), which was also detected in tap water, with sequences similar to those in raw water and after treatment. This indicates that HEV had passed through the treatment and entered into the supply network. However, the viability of the viruses is unknown. In tap water 10-130 International Units of HEV RNA/mL were identified, which is a comparable low amount of virus. The risk of getting infected through consumption of tap water is probably negligible, but needs to be investigated. The HEV strains in the waters belonged to subtypes HEV3a and HEV3c/i, which is associated with unknown source of infection in humans infected in Sweden. None of these subtypes are common among pigs or wild boar, the major reservoirs for HEV, indicating that water may play a role in transmitting this virus. The results indicate that monitoring small fecal/oral transmitted viruses in DWTPs may be considered, especially during community outbreaks, to prevent potential transmission by tap water.
MeSH term(s)	Animals ; Genotype ; Hepatitis E virus ; Humans ; Phylogeny ; RNA, Viral ; Sweden ; Swine ; Swine Diseases ; Viruses
Chemical Substances	RNA, Viral
Language	English
Publishing date	2019-09-30
Publishing country	England
Document type	Journal Article
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2019.115141
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Article ; Online: Building a precision medicine infrastructure at a national level: The Swedish experience.

Edsjö, Anders / Lindstrand, Anna / Gisselsson, David / Mölling, Paula / Friedman, Mikaela / Cavelier, Lucia / Johansson, Maria / Ehrencrona, Hans / Fagerqvist, Therese / Strid, Tobias / Lovmar, Lovisa / Jacobsson, Bo / Johansson, Åsa / Engstrand, Lars / Wheelock, Craig E / Sikora, Per / Wirta, Valtteri / Fioretos, Thoas / Rosenquist, Richard

Cambridge prisms. Precision medicine

2023 Volume 1, Page(s) e15

Abstract: Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique ...

Abstract	Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article ; Review
ISSN	2752-6143
ISSN (online)	2752-6143
DOI	10.1017/pcm.2023.3
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Article ; Online: Comparative Transcriptomics of Sijung and Jumli Marshi Rice during Early Chilling Stress Imply Multiple Protective Mechanisms.

Lindlöf, Angelica / Chawade, Aakash / Sikora, Per / Olsson, Olof

PloS one

2015 Volume 10, Issue 5, Page(s) e0125385

Abstract: Introduction: Low temperature is one of the major environmental factors that adversely affect plant growth and yield. Many cereal crops from tropical regions, such as rice, are chilling sensitive and, therefore, are affected already at <10 °C. ... ...

Abstract	Introduction: Low temperature is one of the major environmental factors that adversely affect plant growth and yield. Many cereal crops from tropical regions, such as rice, are chilling sensitive and, therefore, are affected already at <10 °C. Interestingly, it has been demonstrated that chilling susceptibility varies greatly among rice varieties, which indicates differences in the underlying molecular responses. Understanding these differences is vital for continued development of rational breeding and transgenic strategies for more tolerant varieties. Thus, in this study, we conducted a comparative global gene expression profiling analysis of the chilling tolerant varieties Sijung and Jumli Marshi (spp. Japonica) during early chilling stress (<24 h, 10 °C). Methods and results: Global gene expression experiments were conducted with Agilent Rice Gene Expression Microarray 4 x 44 K. The analysed results showed that there was a relatively low (percentage or number) overlap in differentially expressed genes in the two varieties and that substantially more genes were up-regulated in Jumli Marshi than in Sijung but the number of down-regulated genes were higher in Sijung. In broad GO annotation terms, the activated response pathways in Sijung and Jumli Marshi were coherent, as a majority of the genes belonged to the catalytic, transcription regulator or transporter activity categories. However, a more detailed analysis revealed essential differences. For example, in Sijung, activation of calcium and phosphorylation signaling pathways, as well as of lipid transporters and exocytosis-related proteins take place very early in the stress response. Such responses can be coupled to processes aimed at strengthening the cell wall and plasma membrane against disruption. On the contrary, in Jumli Marshi, sugar production, detoxification, ROS scavenging, protection of chloroplast translation, and plausibly the activation of the jasmonic acid pathway were the very first response activities. These can instead be coupled to detoxification processes. Conclusions: Based on the results inferred from this study, we conclude that different, but overlapping, strategies are undertaken by the two varieties to cope with the chilling stress; in Sijung the initial molecular responses seem to be mainly targeted at strengthening the cell wall and plasma membrane, whereas in Jumli Marshi the protection of chloroplast translation and detoxification is prioritized.
MeSH term(s)	Chlorophyll/metabolism ; Cold Temperature ; Comparative Genomic Hybridization ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Oryza/genetics ; Oryza/growth & development ; Oryza/metabolism ; Phosphorylation ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Signal Transduction ; Stress, Physiological ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Plant Proteins ; Transcription Factors ; Chlorophyll (1406-65-1)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0125385
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Article ; Online: Optimization of cerebrospinal fluid microbial DNA metagenomic sequencing diagnostics.

Olausson, Josefin / Brunet, Sofia / Vracar, Diana / Tian, Yarong / Abrahamsson, Sanna / Meghadri, Sri Harsha / Sikora, Per / Lind Karlberg, Maria / Jakobsson, Hedvig E / Tang, Ka-Wei

Scientific reports

2022 Volume 12, Issue 1, Page(s) 3378

Abstract: Infection in the central nervous system is a severe condition associated with high morbidity and mortality. Despite ample testing, the majority of encephalitis and meningitis cases remain undiagnosed. Metagenomic sequencing of cerebrospinal fluid has ... ...

Abstract	Infection in the central nervous system is a severe condition associated with high morbidity and mortality. Despite ample testing, the majority of encephalitis and meningitis cases remain undiagnosed. Metagenomic sequencing of cerebrospinal fluid has emerged as an unbiased approach to identify rare microbes and novel pathogens. However, several major hurdles remain, including establishment of individual limits of detection, removal of false positives and implementation of universal controls. Twenty-one cerebrospinal fluid samples, in which a known pathogen had been positively identified by available clinical techniques, were subjected to metagenomic DNA sequencing. Fourteen samples contained minute levels of Epstein-Barr virus. The detection threshold for each sample was calculated by using the total leukocyte content in the sample and environmental contaminants found in the bioinformatic classifiers. Virus sequences were detected in all ten samples, in which more than one read was expected according to the calculations. Conversely, no viral reads were detected in seven out of eight samples, in which less than one read was expected according to the calculations. False positive pathogens of computational or environmental origin were readily identified, by using a commonly available cell control. For bacteria, additional filters including a comparison between classifiers removed the remaining false positives and alleviated pathogen identification. Here we show a generalizable method for identification of pathogen species using DNA metagenomic sequencing. The choice of bioinformatic method mainly affected the efficiency of pathogen identification, but not the sensitivity of detection. Identification of pathogens requires multiple filtering steps including read distribution, sequence diversity and complementary verification of pathogen reads.
MeSH term(s)	Cerebrospinal Fluid/microbiology ; DNA ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/methods ; Sequence Analysis, DNA
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-07260-x
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Article ; Online: Variations among Viruses in Influent Water and Effluent Water at a Wastewater Plant over One Year as Assessed by Quantitative PCR and Metagenomics.

Wang, Hao / Neyvaldt, Julianna / Enache, Lucica / Sikora, Per / Mattsson, Ann / Johansson, Anette / Lindh, Magnus / Bergstedt, Olof / Norder, Helene

Applied and environmental microbiology

2020 Volume 86, Issue 24

Abstract: Influent wastewater and effluent wastewater at the Rya treatment plant in Gothenburg, Sweden, were continuously monitored for enteric viruses by quantitative PCR (qPCR) during 1 year. Viruses in effluent wastewater were also identified by next-generation ...

Abstract	Influent wastewater and effluent wastewater at the Rya treatment plant in Gothenburg, Sweden, were continuously monitored for enteric viruses by quantitative PCR (qPCR) during 1 year. Viruses in effluent wastewater were also identified by next-generation sequencing (NGS) in samples collected during spring, early summer, and winter. Samples of incoming wastewater were collected every second week. Seasonal variations in viral concentrations in incoming wastewater were found for noroviruses GII, sapovirus, rotavirus, parechovirus, and astrovirus. Norovirus GI and GIV and Aichi virus were present in various amounts during most weeks throughout the year, while hepatitis A virus, enterovirus, and adenovirus were identified less frequently. Fluctuations in viral concentrations in incoming wastewater were related to the number of diagnosed patients. The viruses were also detected in treated wastewater, however, with a 3- to 6-log
MeSH term(s)	Metagenome ; Metagenomics ; Real-Time Polymerase Chain Reaction ; Seasons ; Virus Physiological Phenomena ; Viruses/classification ; Viruses/genetics ; Viruses/isolation & purification ; Waste Water/virology
Chemical Substances	Waste Water
Language	English
Publishing date	2020-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/AEM.02073-20
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Article ; Online: γ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1.

Darin, Niklas / Leckström, Karin / Sikora, Per / Lindgren, Julia / Almén, Gabriella / Asin-Cayuela, Jorge

European journal of human genetics : EJHG

2018 Volume 26, Issue 6, Page(s) 808–817

Abstract: γ-Glutamyl transpeptidase deficiency (glutathionuria, OMIM 231950) is a rare disease, with only six patients reported in the literature, although this condition has probably been underdiagnosed due the difficulty to routinely analyze glutathione in ... ...

Abstract	γ-Glutamyl transpeptidase deficiency (glutathionuria, OMIM 231950) is a rare disease, with only six patients reported in the literature, although this condition has probably been underdiagnosed due the difficulty to routinely analyze glutathione in clinical samples and to the fact that no genetic defect has been coupled to the disease so far. We report two siblings with mild psychomotor developmental delay and mild neurological symptoms, who presented a markedly increased excretion of glutathione in urine and a very low γ-glutamyl transpeptidase activity in serum. Whole-genome sequencing revealed the presence of a 16.9 kb homozygous deletion in GGT1, one of the genes encoding enzymes with γ-glutamyl transpeptidase activity in the human genome. Close analysis revealed the presence of a 13 bp insertion at the deletion junction. This is the first report of a genetic variant as the cause of glutathionuria. In addition, genetic characterization of the patients' parents and a healthy sibling has provided direct genetic evidence regarding the autosomal recessive nature of this disease.
MeSH term(s)	Adolescent ; Adult ; Amino Acid Metabolism, Inborn Errors/diagnostic imaging ; Amino Acid Metabolism, Inborn Errors/genetics ; Amino Acid Metabolism, Inborn Errors/physiopathology ; Child ; Child, Preschool ; Genome, Human/genetics ; Glutathione/genetics ; Glutathione/metabolism ; Homozygote ; Humans ; Magnetic Resonance Imaging ; Sequence Deletion/genetics ; Whole Genome Sequencing ; Young Adult ; gamma-Glutamyltransferase/deficiency ; gamma-Glutamyltransferase/genetics
Chemical Substances	gamma-Glutamyltransferase (EC 2.3.2.2) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2018-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/s41431-018-0122-6
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Article ; Online: β-Mannosidosis caused by a novel homozygous intragenic inverted duplication in

Blomqvist, Maria / Smeland, Marie Falkenberg / Lindgren, Julia / Sikora, Per / Riise Stensland, Hilde Monica Frostad / Asin-Cayuela, Jorge

Cold Spring Harbor molecular case studies

2019 Volume 5, Issue 3

Abstract: β-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme β-mannosidase. The disease is caused by mutations ... ...

Abstract	β-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme β-mannosidase. The disease is caused by mutations in
MeSH term(s)	Adolescent ; Angiokeratoma/diagnosis ; Angiokeratoma/genetics ; Angiokeratoma/pathology ; DNA Copy Number Variations ; DNA, Complementary/genetics ; Exons/genetics ; Female ; Gene Duplication ; Hearing Loss/genetics ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; Intellectual Disability/genetics ; Mannosidases/genetics ; Mutation ; Phenotype ; Sequence Analysis, DNA ; Whole Genome Sequencing ; beta-Mannosidosis/diagnosis ; beta-Mannosidosis/genetics ; beta-Mannosidosis/pathology
Chemical Substances	DNA, Complementary ; MANBA protein, human (EC 3.2.1.-) ; Mannosidases (EC 3.2.1.-)
Language	English
Publishing date	2019-06-03
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835759-0
ISSN	2373-2873 ; 2373-2873
ISSN (online)	2373-2873
ISSN	2373-2873
DOI	10.1101/mcs.a003954
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