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Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer

View Article: PubMed Central - PubMed

ABSTRACT

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.

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Related in: MedlinePlus

(A) Depiction of genetic relatedness based on a core genome allele by allele comparison of all ST-41/44 complex meningococci (n = 513) in the Meningitis Research Foundation Meningococcus Genome Library, representing all invasive isolates from the United Kingdom and Ireland. Outbreak isolates are highlighted in the light blue oval. (B) Individual cluster of 112 ST-154/ST-1194 meningococci, including variants. Highlighted are 11 ST-6697 strains (blue oval) including carried strains (n = 8, purple triangles) and invasive strains (n = 3, circles). An example of ST-6697 from the general population is indicated by the green circle, and cases B and H are represented by orange circles. Scale bars represent the counts of the observed differences at the 1,605 alleles compared. (C) Enlarged blue oval from panel (B) with 11 outbreak-related meningococcal highlighted as before.
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Figure 1: (A) Depiction of genetic relatedness based on a core genome allele by allele comparison of all ST-41/44 complex meningococci (n = 513) in the Meningitis Research Foundation Meningococcus Genome Library, representing all invasive isolates from the United Kingdom and Ireland. Outbreak isolates are highlighted in the light blue oval. (B) Individual cluster of 112 ST-154/ST-1194 meningococci, including variants. Highlighted are 11 ST-6697 strains (blue oval) including carried strains (n = 8, purple triangles) and invasive strains (n = 3, circles). An example of ST-6697 from the general population is indicated by the green circle, and cases B and H are represented by orange circles. Scale bars represent the counts of the observed differences at the 1,605 alleles compared. (C) Enlarged blue oval from panel (B) with 11 outbreak-related meningococcal highlighted as before.

Mentions: Real-time PCR confirmed the presence of both meningococcal DNA and serogroup B capsular polysaccharide synthesis genes in all case-associated specimens received in the Irish Meningococcal and Meningitis Reference Laboratory (IMMRL). Case B and H isolates were identified as B:4:P1.7-2,4:ST-6697(cc41/44) with FetA VRs F1-21 and F5-12, respectively (Table 1). Case C and E isolates were identified as ST-6697(cc41/44). Incomplete MLST profiles were obtained for cases A (aroE and pgm) and F (abcZ and pgm) but were identical at the typed loci to those in the outbreak strain ST6697 (Table 1). All six strains shared the PorA VR type P1.7-2,4. A comparison of the ST6697 strains from this outbreak and the cc41/44 invasive isolates in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) revealed the rare nature of this ST, where all outbreak-related isolates clustered together and branched off a clade composed of ST154 or ST154 variants (Fig. 1).


Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer
(A) Depiction of genetic relatedness based on a core genome allele by allele comparison of all ST-41/44 complex meningococci (n = 513) in the Meningitis Research Foundation Meningococcus Genome Library, representing all invasive isolates from the United Kingdom and Ireland. Outbreak isolates are highlighted in the light blue oval. (B) Individual cluster of 112 ST-154/ST-1194 meningococci, including variants. Highlighted are 11 ST-6697 strains (blue oval) including carried strains (n = 8, purple triangles) and invasive strains (n = 3, circles). An example of ST-6697 from the general population is indicated by the green circle, and cases B and H are represented by orange circles. Scale bars represent the counts of the observed differences at the 1,605 alleles compared. (C) Enlarged blue oval from panel (B) with 11 outbreak-related meningococcal highlighted as before.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121376&req=5

Figure 1: (A) Depiction of genetic relatedness based on a core genome allele by allele comparison of all ST-41/44 complex meningococci (n = 513) in the Meningitis Research Foundation Meningococcus Genome Library, representing all invasive isolates from the United Kingdom and Ireland. Outbreak isolates are highlighted in the light blue oval. (B) Individual cluster of 112 ST-154/ST-1194 meningococci, including variants. Highlighted are 11 ST-6697 strains (blue oval) including carried strains (n = 8, purple triangles) and invasive strains (n = 3, circles). An example of ST-6697 from the general population is indicated by the green circle, and cases B and H are represented by orange circles. Scale bars represent the counts of the observed differences at the 1,605 alleles compared. (C) Enlarged blue oval from panel (B) with 11 outbreak-related meningococcal highlighted as before.
Mentions: Real-time PCR confirmed the presence of both meningococcal DNA and serogroup B capsular polysaccharide synthesis genes in all case-associated specimens received in the Irish Meningococcal and Meningitis Reference Laboratory (IMMRL). Case B and H isolates were identified as B:4:P1.7-2,4:ST-6697(cc41/44) with FetA VRs F1-21 and F5-12, respectively (Table 1). Case C and E isolates were identified as ST-6697(cc41/44). Incomplete MLST profiles were obtained for cases A (aroE and pgm) and F (abcZ and pgm) but were identical at the typed loci to those in the outbreak strain ST6697 (Table 1). All six strains shared the PorA VR type P1.7-2,4. A comparison of the ST6697 strains from this outbreak and the cc41/44 invasive isolates in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) revealed the rare nature of this ST, where all outbreak-related isolates clustered together and branched off a clade composed of ST154 or ST154 variants (Fig. 1).

View Article: PubMed Central - PubMed

ABSTRACT

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.

No MeSH data available.


Related in: MedlinePlus