| 1. |
- Eriksson, Lorraine, 1990-, et al.
(författare)
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Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice
- 2020
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Ingår i: BMC Microbiology. - : BioMed Central. - 1471-2180. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neisseria meningitidis serogroups W and Y are the most common serogroups causing invasive meningococcal disease in Sweden. The majority of cases are caused by the serogroup W UK 2013 strain of clonal complex (cc) 11, and subtype 1 of the serogroup Y, YI strain of cc23. In this study, virulence factors of several lineages within cc11 and cc23 were investigated in transgenic BALB/c mice expressing human transferrin. Transgenic mice were infected intraperitoneally with serogroup W and Y isolates. Levels of bacteria and the proinflammatory cytokine CXCL1 were determined in blood collected 3 h and 24 h post-infection. Apoptosis was investigated in immune cells from peritoneal washes of infected mice. Adhesion and induction of apoptosis in human epithelial cells were also scored.RESULTS: The levels of bacteraemia, CXCL1, and apoptosis were higher in serogroup W infected mice than in serogroup Y infected mice. Serogroup W isolates also induced higher levels of apoptosis and adhesion in human epithelial cells. No significant differences were observed between different lineages within cc11 and cc23.CONCLUSIONS: N. meningitidis Serogroup W displayed a higher virulence in vivo in transgenic mice, compared to serogroup Y. This was reflected by higher bacteremia, proinflammatory activity, and ability to induce apoptosis in mouse immune cells and human epithelial cells.
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| 2. |
- Eriksson, Lorraine, 1990-
(författare)
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Exploring genomic and phenotypic differences in Neisseria meningitidis : understanding carriage and invasive disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neisseria meningitidis can colonise the nasopharynx in humans and is also the cause of invasive meningococcal disease (IMD), which often presents as septicaemia and meningitis with high mortality rates. Invasive disease is often associated with specific capsular serogroups and clonal complexes (CC). In Sweden, serogroups Y and W have had a high incidence in recent years, but were previously considered rare causes of IMD, suggesting a change in the virulence potential of these serogroups. Currently, no specific genes exist that can reliably predict whether an N. meningitidis isolate will result in invasive disease or remain in the carriage state. Genetically similar isolates can be found during carriage and IMD, and it is more common for the carriage isolates to lack a capsule. The aim of this thesis was to investigate how genetic and phenotypic differences in N. meningitidis, can affect the virulence and the transition from a carriage state to invasive disease.The results indicate that the increase of serogroup W in Sweden is due to a specific lineage of CC11. This CC is rarely found among carriers and is considered highly virulent. Infections in transgenic mice with serogroup W CC11 isolates showed a greater virulence compared to serogroup Y isolates from other CCs. Although both serogroups are common causes of IMD in Sweden, they differ in virulence in transgenic mice. A genome-wide association study comparing carriage and invasive isolates, revealed that there were genetic variants in genes associated with virulence between these isolates. Among these variants were pilE/pilS, which are involved in the type IV pili. Comparison of pilE gene expression between carriage and invasive isolates showed no significant difference between these isolates. However, a difference in the class of the PilE protein was found between invasive and carriage isolates. Further research is needed to understand the impact of these genetic variations on the transition from carriage to invasive disease, also considering how factors in the human host and the environment that may contribute to the development of invasive disease.
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| 3. |
- Eriksson, Lorraine, 1990-, et al.
(författare)
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Genetic variants linked to the phenotypic outcome of invasive disease and carriage of Neisseria meningitidis
- 2023
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis can be a human commensal in the upper respiratory tract but is also capable of causing invasive diseases such as meningococcal meningitis and septicaemia. No specific genetic markers have been detected to distinguish carriage from disease isolates. The aim here was to find genetic traits that could be linked to phenotypic outcomes associated with carriage versus invasive N. meningitidis disease through a bacterial genome-wide association study (GWAS). In this study, invasive N. meningitidis isolates collected in Sweden (n=103) and carriage isolates collected at Örebro University, Sweden (n=213) 2018-2019 were analysed. The GWAS analysis, treeWAS, was applied to single-nucleotide polymorphisms (SNPs), genes and k-mers. One gene and one non-synonymous SNP were associated with invasive disease and seven genes and one non-synonymous SNP were associated with carriage isolates. The gene associated with invasive disease encodes a phage transposase (NEIS1048), and the associated invasive SNP glmU S373C encodes the enzyme N-acetylglucosamine 1-phosphate (GlcNAC 1-P) uridyltransferase. Of the genes associated with carriage isolates, a gene variant of porB encoding PorB class 3, the genes pilE/pilS and tspB have known functions. The SNP associated with carriage was fkbp D33N, encoding a FK506-binding protein (FKBP). K-mers from PilS, tbpB and tspB were found to be associated with carriage, while k-mers from mtrD and tbpA were associated with invasiveness. In the genes fkbp, glmU, PilC and pilE, k-mers were found that were associated with both carriage and invasive isolates, indicating that specific variations within these genes could play a role in invasiveness. The data presented here highlight genetic traits that are significantly associated with invasive or carriage N. meningitidis across the species population. These traits could prove essential to our understanding of the pathogenicity of N. meningitidis and could help to identify future vaccine targets.
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| 4. |
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| 5. |
- Eriksson, Lorraine, 1990-, et al.
(författare)
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Whole-Genome Sequencing of Emerging Invasive Neisseria meningitidis Serogroup W in Sweden
- 2018
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 56:4
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Tidskriftsartikel (refereegranskat)abstract
- Invasive disease caused by Neisseria meningitidis serogroup W (MenW) has historically had a low incidence in Sweden, with an average incidence of 0.03 case/100,000 population from 1995 to 2014. In recent years, a significant increase in the incidence of MenW has been noted in Sweden, to an average incidence of 0.15 case/100,000 population in 2015 to 2016. In 2017 (1 January to 30 June), 33% of invasive meningococcal disease cases (7/21 cases) were caused by MenW. In the present study, all invasive MenW isolates from Sweden collected in 1995 to June 2017 (n = 86) were subjected to whole-genome sequencing to determine the population structure and to compare isolates from Sweden with historical and international cases. The increase of MenW in Sweden was determined to be due to isolates belonging to the South American sublineage of MenW clonal complex 11, namely, the novel U.K. 2013 lineage. This lineage was introduced in Sweden in 2013 and has since been the dominant lineage of MenW.
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| 6. |
- Hedberg, Sara Thulin, et al.
(författare)
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Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006 : phenotypic and genotypic perspectives
- 2009
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 53:4, s. 1561-1566
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Tidskriftsartikel (refereegranskat)abstract
- Up-to-date information regarding the antibiotic susceptibility of Neisseria meningitidis strains from African countries is highly limited. Our aim was to comprehensively describe the antibiotic susceptibilities of a selection of N. meningitidis isolates recovered between 2000 and 2006 from 18 African countries, mainly those within the meningitis belt. Susceptibilities to 11 antibiotics were determined using Etest for 137 N. meningitidis isolates (stringently selected from 693 available isolates). The isolates were also characterized by serogrouping, multilocus sequence typing, genosubtyping, and penA allele identification. All N. meningitidis isolates were susceptible to ceftriaxone, chloramphenicol, and ciprofloxacin. No isolate produced beta-lactamase. Only three isolates (2%) displayed reduced susceptibility to penicillin G. The two isolates with the highest penicillin G MICs were the only isolates showing reduced susceptibility to ampicillin and cefuroxime. One of these isolates was also resistant to penicillin V. One percent of isolates displayed reduced susceptibility to rifampin, while 52% of the isolates were resistant to tetracycline, 74% were resistant to erythromycin, and 94% were resistant to sulfadiazine. The MICs of rifampin and tetracycline seemed to be associated with the serogroup of the isolates. In total, 18 sequence types (STs), 10 genosubtypes, and 8 different penA alleles were identified; the most common were ST-7, P1.20,9,35-1, and penA4, respectively. A high level of correlation was found between ST, genosubtype, and penA allele. In conclusion, N. meningitidis isolates from the African meningitis belt remain highly susceptible to the antibiotics used. Regarding beta-lactam antibiotics, rare isolates showed a reduced susceptibility to penicillins, but the expanded-spectrum cephalosporins are not affected at present.
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| 7. |
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| 8. |
- Hedberg, Sara Thulin, et al.
(författare)
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Combined real-time PCR and pyrosequencing strategy for objective, sensitive, specific, and high throughput identification of reduced susceptibility to penicillins in Neisseria meningitidis
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - Washington, DC : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 52:2, s. 753-756
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Tidskriftsartikel (refereegranskat)abstract
- A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Pen(i)-specific sites and reduced susceptibility to penicillins was identified.
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| 9. |
- Hedberg, Sara Thulin, 1980-, et al.
(författare)
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Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010
- 2011
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Ingår i: Eurosurveillance. - Saint-Maurice, France : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 16:23
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Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis serogroups B and C have beenresponsible for the majority of invasive meningococcaldisease in Europe. Recently, an increase of N. meningitidisdisease due to serogroup Y has been notedin Sweden (in 2010, the proportion was 39%, with anincidence of 0.23 per 100,000 population), as well as inother northern European countries. We aimed to investigatethe clonal pattern of the emerging serogroup Yin Sweden during 2000 to 2010. The serogroup Y isolatesidentified during this time (n=85) were characterisedby multilocus sequence typing and sequencing ofthe fetA, fHbp, penA, porA and porB genes. The mostfrequent clone (comprising 28 isolates) with identicalallele combinations of the investigated genes, waspartly responsible for the observed increased numberof N. meningitidis serogroup Y isolates. It was sulfadiazineresistant, with genosubtype P1.5-2,10-1,36-2,sequence type 23, clonal complex 23, porB allele 3-36,fetA allele F4-1, fHbp allele 25 and penA allele 22. Thefirst case with disease due to this clone was identifiedin 2002: there was a further case in 2004, six during2006 to 2007, eight during 2008 to 2009, with a peakof 12 cases in 2010. An unusual increase of invasivedisease in young adults (aged 20–29 years) caused bythis clone was shown, but no increase in mortality ratewas observed.
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