| 1. |
- Stenmark, Bianca, 1987-, et al.
(författare)
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Complete genome and methylome analysis of Neisseria meningitidis associated with increased serogroup Y disease
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis emerged in Europe during the 2000s. Draft genomes of serogroup Y isolates in Sweden revealed that although the population structure of these isolates was similar to other serogroup Y isolates internationally, a distinct strain (YI) and more specifically a sublineage (1) of this strain was responsible for the increase of serogroup Y IMD in Sweden. We performed single molecule real-time (SMRT) sequencing on eight serogroup Y isolates from different sublineages to unravel the genetic and epigenetic factors delineating them, in order to understand the serogroup Y emergence. Extensive comparisons between the serogroup Y sublineages of all coding sequences, complex genomic regions, intergenic regions, and methylation motifs revealed small point mutations in genes mainly encoding hypothetical and metabolic proteins, and non-synonymous variants in genes involved in adhesion, iron acquisition, and endotoxin production. The methylation motif CACNNNNNTAC was only found in isolates of sublineage 2. Only seven genes were putatively differentially expressed, and another two genes encoding hypothetical proteins were only present in sublineage 2. These data suggest that the serogroup Y IMD increase in Sweden was most probably due to small changes in genes important for colonization and transmission.
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| 2. |
- Stenmark, Bianca, 1987-, et al.
(författare)
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Complete genome and methylome comparison of two Neisseria meningitidis serogroup Y subtypes
- 2017
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Ingår i: 2nd ASM Conference on Rapid Applied Microbial Next-Generation Sequencing and Bioinformatic Pipelines. - Washington, DC : American Society for Microbiology. ; , s. 32-33
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: A significant increase in invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (MenY) strains emerged in the United States during the 1990s spreading to Europe shortly thereafter. The largest increase was observed in Sweden with incidence proportions up to 53%. cgMLST of all MenY isolates causing IMD between 1995 to 2012 in Sweden revealed that a distinct strain (YI) and more specifically a subtype (1) of this strain was found to be responsible for the increase of MenY IMD in Sweden [1]. The aim was to compare the complete genome and methylome of subtype 1 to the less successful subtype 2 using Single Molecule Real-Time (SMRT) sequencing technology.Methods: Ten genomes belonging to subtype 1 (n=7) and 2 (n=3) and one MenY genome without connection to a specific strain were sequenced using SMRT sequencing on a PacBio®RS II. SMRT Portal v2 was used to identify modified positions and for the genome-wide analysis of modified motifs. DNA methyltransferase genes associated with the different methyltransferase recognition motifs identified were searched using the Restriction Enzyme Database REBASE (rebase.neb.com).Results: Genomic comparison of the two MenY subtypes revealed that these possessed highly similar genomes, only two genes encoding hypothetical proteins were present in subtype 2 but absent in subtype 1. There were 99 genes with allelic differences and non-synonymous differences were found in genes implicated in adhesion, lipooligosaccharides (LOS) production, pilin production and iron acquisition. The genome-wide analysis of the methylome identified three modified motifs: GATC, GGNNCC and CACNNNNNTAC, the latter was only found in isolates belonging to subtype 2 and a trans-posase was found inserted in the candidate enzyme: a type I restriction system specificity protein (NEIS2535). In general, modifications were found in both cytosine and adenine bases although the latter, 6mA, was the most frequent modification in all isolates and more predominant among subtype 2. Many inactive restriction modification systems were present; however, in order to reveal more active sys-tems, further analysis on 5mC is needed.Conclusion: Our preliminary results indicate that there is a difference in methylation motifs as well as positional distribution of modifications between the two MenY subtypes. Since no differences were found in the presence of genes potentially involved in pathogenicity between the two subtypes, and it has been previously established that there was rather a tendency of a milder clinical picture among IMD caused by subtype 1 [2], the emergence of subtype 1 was most probably due to increased transmission or that the human population was more immunologically naïve to this subtype.References: 1. Törös B et al. J Clin Microbiol 2015, 53(7):2154-2162. 2. Säll O et al.Epidemiol Infect 2017, 145(10):2137-2143.
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| 3. |
- Stenmark, Bianca, 1987-, et al.
(författare)
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Genome-wide methylome analysis of two strains belonging to the hypervirulent Neisseria meningitidis serogroup W ST-11 clonal complex
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide. Serogroup W isolates belonging to the sequence type (ST)-11 clonal complex have been associated with atypical symptoms and increased case fatality rates. The continued expansion of this clonal complex in the later part of the 2010s has been largely due to a shift from the so-called original UK strain to the 2013 strain. Here we used single-molecule real-time (SMRT) sequencing to determine the methylomes of the two major serogroup W strains belonging to ST-11 clonal complex. Five methylated motifs were identified in this study, and three of the motifs, namely 5'-GATC-3', 5'-GAAGG-3', 5'-GCGCGC-3', were found in all 13 isolates investigated. The results showed no strain-specific motifs or difference in active restriction modification systems between the two strains. Two phase variable methylases were identified and the enrichment or depletion of the methylation motifs generated by these methylases varied between the two strains. Results from this work give further insight into the low diversity of methylomes in highly related strains and encourage further research to decipher the role of regions with under- or overrepresented methylation motifs.
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| 4. |
- Titov, Leonid P., et al.
(författare)
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Evolutionary epidemiology of Neisseria meningitidis strains in Belarus compared to other European countries
- 2013
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Ingår i: Acta Microbiologica et Immunologica Hungarica. - 1217-8950. ; 60:4, s. 397-410
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Meningococcal infections are major causes of death in children globally. In Belarus, the incidence of cases and fatality rate of meningococcal infections are low and comparable to the levels in other European countries. Aim. In the present study, the molecular and epidemiological traits of Neisseria meningitidis strains circulating in Belarus were characterized and compared to isolates from other European countries. Materials and Methods. Twenty N. meningitidis strains isolated from patients (n = 13) and healthy contacts (n = 7) during 2006-2012 in Belarus were selected for multilocus sequence typing (MLST), genosubtyping and FetA typing. The STs of the Belarusian strains were phylogenetically compared to the STs of 110 selected strains from 22 other European countries. Results. Overall, eleven different genosubtypes were observed, there were seven variants of variable region of the fetA gene detected. The majority of the STs (95%) found in Belarus were novel and all those were submitted to the Neisseria MLST database for assignment. Several newly discovered alleles of fumC (allele 451) and gdh (allele 560 and 621) appeared to be descendants of alleles which are widespread in Europe, and single aroE alleles (602 and 603) occurred as a result of separate evolution. Conclusions. N. meningitidis strains circulating in Belarus are heterogeneous and include sequence types, possibly, locally evolved in Belarus as well as representatives of widespread European hyperinvasive clonal complexes.
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| 5. |
- Törös, B., et al.
(författare)
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Surveillance of invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 2012
- 2014
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 19:42, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- An increase of invasive meningococcal disease caused by Neisseria meningitidis serogroup Y has been noted in Sweden since 2005, and to a lower extent throughout Europe. The present study describes the epidemiology of invasive N. meningitidis isolates in Sweden in the period between 2010 and 2012, with a focus on serogroup Y. We also aimed to find an optimal molecular typing scheme for both surveillance and outbreak investigations. All invasive N. meningitidis isolates in Sweden during the study period (n=208) were genetically characterised. Serogroup Y predominated with 22/57, 31/61 and 44/90 of all invasive isolates (incidence 0.23, 0.33 and 0.46 per 100,000 population) in 2010, 2011 and 2012 respectively. In each of these years, 15/22, 22/31 and 19/44 of serogroup Y isolates were genetically clonal (Y: P1.5-2,10-1,36-2: F4-1: ST-23(cc23), 'porB allele 3-36, fHbp allele 25 and penA allele 22). Our findings further support those of others that currently recommended FetA typing could be replaced by FHbp. Moreover, in line with a previous study that we conducted, the current results indicate that highly variable multilocus variable-number tandem repeat analysis (HV-MLVA) can be used as a first-hand rapid method for small outbreak investigations.
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