Genome-wide methylome analysis of two strains belonging to the hypervirulent Neisseria meningitidis serogroup W ST-11 clonal complex

Bianca Stenmark,Sara Thulin Hedberg,Paula Mölling,Richard J Roberts,Brian P Anton,Alexey Fomenkov,Lorraine Eriksson

doi:10.1038/s41598-021-85266-7

Bianca Stenmark, Sara Thulin Hedberg + Show 5 more

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https://doi.org/10.1038/s41598-021-85266-7

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Abstract

A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide. Serogroup W isolates belonging to the sequence type (ST)-11 clonal complex have been associated with atypical symptoms and increased case fatality rates. The continued expansion of this clonal complex in the later part of the 2010s has been largely due to a shift from the so-called original UK strain to the 2013 strain. Here we used single-molecule real-time (SMRT) sequencing to determine the methylomes of the two major serogroup W strains belonging to ST-11 clonal complex. Five methylated motifs were identified in this study, and three of the motifs, namely 5′-GATC-3′, 5′-GAAGG-3′, 5′-GCGCGC-3′, were found in all 13 isolates investigated. The results showed no strain-specific motifs or difference in active restriction modification systems between the two strains. Two phase variable methylases were identified and the enrichment or depletion of the methylation motifs generated by these methylases varied between the two strains. Results from this work give further insight into the low diversity of methylomes in highly related strains and encourage further research to decipher the role of regions with under- or overrepresented methylation motifs.

Highlights

A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide
Invasive meningococcal disease due to meningococcal serogroup W (MenW) emerged in Sub-Saharan Africa following the outbreak in Hajj pilgrims in 2 0004 and later on in South Africa[5] and South America[6]
Whole-genome sequencing has revealed two strains belonging to the sequence type (ST)-11 clonal complex, one which predominated in the UK before 2013, referred to as the original UK strain, and one that emerged after 2013, the 2013-strain[11], which has predominated in Sweden since 201312

Summary

Introduction

A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide. Serogroup W isolates belonging to the sequence type (ST)-11 clonal complex have been associated with atypical symptoms and increased case fatality rates. We used single-molecule real-time (SMRT) sequencing to determine the methylomes of the two major serogroup W strains belonging to ST-11 clonal complex. Whole-genome sequencing has revealed two strains belonging to the ST-11 clonal complex, one which predominated in the UK before 2013, referred to as the original UK strain, and one that emerged after 2013, the 2013-strain[11], which has predominated in Sweden since 201312. Genome-wide patterns of methylation in bacteria can be studied using Single molecule real-time (SMRT) PacBio sequencing which has the potential to detect all three ways of methylation, but is often unreliable for m5C-containing m otifs[19]

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