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Published on: July 14, 2020
Loss of Genomic Diversity in a Neisseria meningitidis Clone Through a Colonization Bottleneck
Araceli Lamelas1,2,3, Abdul-Wahab M Hamid1,2,4, Jean-Pierre Dangy1,2
1Swiss Tropical and Public Health Institute, Basel, Switzerland.
Abstract:
Neisseria meningitidis is the leading cause of epidemic meningitis in the "meningitis belt" of Africa, where clonal waves of colonization and disease are observed. Point mutations and horizontal gene exchange lead to constant diversification of meningococcal populations during clonal spread. Maintaining a high genomic diversity may be an evolutionary strategy of meningococci that increases chances of fixing occasionally new highly successful "fit genotypes". We have performed a longitudinal study of meningococcal carriage and disease in northern Ghana by analyzing cerebrospinal fluid samples from all suspected meningitis cases and monitoring carriage of meningococci by twice yearly colonization surveys. In the framework of this study, we observed complete replacement of an A: sequence types (ST)-2859 clone by a W: ST-2881 clone. However, after a gap of 1 year, A: ST-2859 meningococci re-emerged both as colonizer and meningitis causing agent. Our whole genome sequencing analyses compared the A population isolated prior to the W colonization and disease wave with the re-emerging A meningococci. This analysis revealed expansion of one clone differing in only one nonsynonymous SNP from several isolates already present in the original A: ST-2859 population. The colonization bottleneck caused by the competing W meningococci thus resulted in a profound reduction in genomic diversity of the A meningococcal population.
Insights
Epidemic meningitis in Africa is driven by Neisseria meningitidis. A W:ST-2881 clone temporarily replaced the A:ST-2859 clone, which later re-emerged, but with significantly reduced genomic diversity due to the colonization bottleneck.
Area of Science:
- Microbiology
- Epidemiology
- Genomics
Background:
- Neisseria meningitidis is a primary cause of epidemic meningitis in Africa's meningitis belt.
- Meningococcal populations diversify through mutations and gene exchange during clonal spread.
- High genomic diversity may be an evolutionary strategy for meningococci to fix successful genotypes.
Purpose of the Study:
- To investigate meningococcal population dynamics and genomic diversity during clonal replacement events in northern Ghana.
- To compare the genomic makeup of Neisseria meningitidis A:ST-2859 before and after a W:ST-2881 clone's dominance.
Main Methods:
- Longitudinal study of meningococcal carriage and disease in northern Ghana.
- Analysis of cerebrospinal fluid from meningitis cases.
- Twice-yearly colonization surveys.
- Whole genome sequencing of Neisseria meningitidis isolates.
Main Results:
- Observed complete replacement of an A:ST-2859 clone by a W:ST-2881 clone.
- A:ST-2859 meningococci re-emerged after a one-year gap as both colonizers and disease agents.
- Whole genome sequencing revealed the re-emerging A:ST-2859 clone differed by only one nonsynonymous SNP from the original population.
- The W clone's dominance caused a significant reduction in the genomic diversity of the A meningococcal population.
Conclusions:
- Colonization bottlenecks, like that caused by competing meningococcal clones, can drastically reduce bacterial genomic diversity.
- Neisseria meningitidis populations exhibit resilience, with previously dominant clones capable of re-emergence after competitive exclusion.
- Understanding these population dynamics is crucial for managing meningitis epidemics in endemic regions.
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