Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad

Kanny Diallo,James M Stuart,James E Bray,Musa Hassan-King,Caroline L Trotter,Dominique A Caugant,Martin C J Maiden,Brian M Greenwood,Olivier Manigart,Doumagoum M Daugla,Odile B Harrison,Kadija Gamougam,Jay Lucidarme

doi:10.1186/s12864-017-3789-0

Abstract

BackgroundSerogroup 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.ResultsAll 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.ConclusionsWhole 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.

Highlights

Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad
Studies compared the proportions of clonal complexes, defined by Multi Locus Sequence Typing (MLST), among serogroups and identified hyper-virulent lineages that were overrepresented in invasive isolates and less common in carriage samples [1]
Comparison of the contig lacking gdh from this isolate with another isolate where gdh was present identified the deletion of six contiguous genes all involved in glucose metabolism, NEIS1325, NEIS1326, NEIS1328 to NEIS1331 (Additional file 1: Figure S1)

Summary

Introduction

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”; the transition from carriage to disease phenotype remains poorly understood. More recent studies have used whole genome technology to compare a broad range of disease and carriage isolates These studies have, for example, identified a prophage present in some disease-associated isolates but not limited to them [2,3,4]. Another recent study compared carried and invasive serogroup Y Nm (NmY) from the UK and identified a disease-associated clone [5]; there is still much uncertainty over what determines the carried or invasive state, especially during epidemics

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