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Published on: July 14, 2020
Origin of Neisseria meningitidis clonal complex 4821
Zhizhou Tan1, Lin Xu2, Jie Che1
1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Abstract:
Neisseria meningitidis (N. meningitidis) is the causative agent of human invasive meningococcal disease (IMD). Clonal complex (CC) 4821 is a unique genetic cluster of N. meningitidis that emerged two decades ago in Anhui Province, China and became the predominant cluster. However, the evolutionary origin of CC4821 remains unclear. Herein, a distinct CC4821 clade was identified by a comprehensive cgMLST analysis of 26,801 N. meningitidis genomes. The CC4821 clade comprised 388 N. meningitidis isolates, with 364 assigned to CC4821, 1 assigned to CC8, and 23 unassigned (UA), as they could not be assigned to any defined CC. The phylogenetic analysis of the CC4821 clade revealed that six UA isolates, including the UA isolate NmR29026 collected in 1966 from Liaoning Province, China, occupied a basal position compared to all isolates within the CC4821 clade, indicating that CC4821 originated in the 1960s. Eight subclades (clades 1-8) were recognized within the CC4821 clade. Clades 1-4 have been present since the 1970s, while clades 5-8 emerged after the 2000s. Clade 5 represents a hyperinvasive lineage. N. meningitidis isolate HEB85-3, collected in 1985 in Hebei Province, China, exhibited the closest evolutionary relationship to clade 5, suggesting it is related to the origin of this hyperinvasive lineage. Our study reveals that CC4821 has emerged as the predominant cluster of N. meningitidis in China, representing the culmination of at least 60 years of continuous evolution in China, and is not solely attributable to the outbreak two decades ago.
Insights
The study traced the origins of the Neisseria meningitidis CC4821 cluster in China, revealing its evolution over 60 years, not just the last two decades. This finding reshapes our understanding of invasive meningococcal disease dynamics.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Neisseria meningitidis causes invasive meningococcal disease (IMD).
- Clonal complex (CC) 4821 is a dominant N. meningitidis genetic cluster in China, emerging ~20 years ago.
- The evolutionary history of CC4821 remains largely unknown.
Purpose of the Study:
- To elucidate the evolutionary origin and timeline of the N. meningitidis CC4821 clade.
- To identify the ancestral lineages and diversification patterns within CC4821.
Main Methods:
- Comprehensive core genome multilocus sequence typing (cgMLST) analysis of 26,801 N. meningitidis genomes.
- Phylogenetic analysis to reconstruct evolutionary relationships and estimate divergence times.
Main Results:
- A distinct CC4821 clade was identified, comprising 388 N. meningitidis isolates.
- Phylogenetic analysis indicated CC4821 originated in the 1960s, with basal isolates dating back to 1966.
- Eight subclades were identified, with clades 1-4 present since the 1970s and clades 5-8 emerging post-2000s.
- Clade 5, a hyperinvasive lineage, likely originated from an isolate from 1985.
Conclusions:
- N. meningitidis CC4821 has a 60-year evolutionary history in China, predating its recent emergence as a predominant cluster.
- The findings highlight continuous evolution and diversification within N. meningitidis in China.
- Understanding the deep evolutionary roots of CC4821 is crucial for predicting and controlling future IMD outbreaks.
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