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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.

No MeSH data available.


Neighbor-Net diagram of the 14 isolates recovered from nasopharyngeal swabs, generated from 1,605 core meningococcal genes. Included are eight ST-6697 isolates (cc41/44), three cc269 isolates, and one isolate each from cc22, cc461, and cc1157.
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Figure 3: Neighbor-Net diagram of the 14 isolates recovered from nasopharyngeal swabs, generated from 1,605 core meningococcal genes. Included are eight ST-6697 isolates (cc41/44), three cc269 isolates, and one isolate each from cc22, cc461, and cc1157.

Mentions: The 14 N. meningitidis isolates cultured that were carried included 12 serogroup B isolates; 8 were identified as B:P1.7-2,4:ST-6697(cc41/44), the outbreak strain. Five clonal complexes were represented among the isolates carried (Fig. 3). Five of the eight ST6697 isolates were from individuals aged 24 to 34 years. Seven ST6697 isolates were recovered from individuals living in trailers (n = 7/45).


Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer
Neighbor-Net diagram of the 14 isolates recovered from nasopharyngeal swabs, generated from 1,605 core meningococcal genes. Included are eight ST-6697 isolates (cc41/44), three cc269 isolates, and one isolate each from cc22, cc461, and cc1157.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Neighbor-Net diagram of the 14 isolates recovered from nasopharyngeal swabs, generated from 1,605 core meningococcal genes. Included are eight ST-6697 isolates (cc41/44), three cc269 isolates, and one isolate each from cc22, cc461, and cc1157.
Mentions: The 14 N. meningitidis isolates cultured that were carried included 12 serogroup B isolates; 8 were identified as B:P1.7-2,4:ST-6697(cc41/44), the outbreak strain. Five clonal complexes were represented among the isolates carried (Fig. 3). Five of the eight ST6697 isolates were from individuals aged 24 to 34 years. Seven ST6697 isolates were recovered from individuals living in trailers (n = 7/45).

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.