Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad
Daugla, Doumagoum M
Harrison, Odile B
Bray, James E
Caugant, Dominique A
Stuart, James M
Greenwood, Brian M
Maiden, Martin CJ
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Diallo, K., Gamougam, K., Daugla, D. M., Harrison, O. B., Bray, J. E., Caugant, D. A., Lucidarme, J., et al. (2017). Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad. https://doi.org/10.1186/s12864-017-3789-0
BACKGROUND: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. RESULTS: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. CONCLUSIONS: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.
The MenAfriCar consortium, funded by the Wellcome Trust (grant number: 086546/Z/08/Z) and the Bill and Melinda Gates Foundation (grant number: 51251) supported the costs of sequencing. Kanny Diallo holds a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine (grant number: 103957/Z/14/Z). The funding sources had no role in the study design, collection, analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication. Martin Maiden was supported by the Wellcome Trust (grant number: 087622/Z/08/Z).
Bill & Melinda Gates Foundation (via London School of Hygiene & Tropical Medicine) (ITDCVT64: UCAM)
External DOI: https://doi.org/10.1186/s12864-017-3789-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266310