Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci.

Mingliang Chen,Martin C.J Maiden,Qinglan Guo,Odile B Harrison,Holly B Bratcher,Xi Zhang,Charlene M.C Rodrigues,Keith A Jolley,James E Bray,Zhiyan Bo,Min Chen

doi:10.3201/eid2704.203612

Abstract

Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the relationship among globally distributed CC4821 meningococci, we analyzed whole-genome sequence data from 173 CC4821 meningococci isolated from 4 continents during 1972–2019. These meningococci clustered into 4 sublineages (1–4); sublineage 1 primarily comprised of IMD isolates (41/50, 82%). Most isolates from outside China (40/49, 81.6%) formed a distinct sublineage, the Europe–USA cluster, with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(CC4821), harboring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. The increasing distribution worldwide of serogroup B CC4821 raises the concern that CC4821 has the potential to cause a pandemic that would be challenging to control, despite indirect evidence that the Trumenba vaccine might afford some protection.

Highlights

Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China
Meningococci are classified into 12 serogroups based on capsular polysaccharides [1]; genetic relationships among isolates are defined by clonal complexes (CCs) identified by multilocus sequence typing (MLST), which are surrogates for lineages [2]
Peng et al identified 6 strain-specific genome regions resulting from horizontal gene transfer (HGT) in isolate 053442 [8]; this finding was consistent with the emergence of the ChinaCC4821-R1-C/B clone associated with multiple HGT events within genes encoding surface antigens [6], the donors of these events were not identified

Summary

Introduction

Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the relationship among globally distributed CC4821 meningococci, we analyzed whole-genome sequence data from 173 CC4821 meningococci isolated from 4 continents during 1972–2019 These meningococci clustered into 4 sublineages [1,2,3,4]; sublineage 1 primarily comprised of IMD isolates (41/50, 82%). Most isolates from outside China (40/49, 81.6%) formed a distinct sublineage, the Europe–USA cluster, with the typical strain designation B:P1.17-6,23:F3-36:ST3200(CC4821), harboring mutations in penicillin-binding protein 2 These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. We assessed genes encoding key antigens and antimicrobial resistance phenotypes, identified putative donors of HGT events unique to the epidemic and quinolone-resistant clone ChinaCC4821-R1-C/B, and characterized isolates outside of China

Methods

Results

Conclusion