Using Single-Nucleotide Polymorphisms To Discriminate Disease-Associated from Carried Genomes of Neisseria meningitidis

Abstract

Neisseria meningitidis is one of the main agents of bacterial meningitis, causing substantial morbidity and mortality worldwide. However, most of the time N. meningitidis is carried as a commensal not associated with invasive disease. The genomic basis of the difference between disease-associated and carried isolates of N. meningitidis may provide critical insight into mechanisms of virulence, yet it has remained elusive. Here, we have taken a comparative genomics approach to interrogate the difference between disease-associated and carried isolates of N. meningitidis at the level of individual nucleotide variations (i.e., single nucleotide polymorphisms [SNPs]). We aligned complete genome sequences of 8 disease-associated and 4 carried isolates of N. meningitidis to search for SNPs that show mutually exclusive patterns of variation between the two groups. We found 63 SNPs that distinguish the 8 disease-associated genomes from the 4 carried genomes of N. meningitidis, which is far more than can be expected by chance alone given the level of nucleotide variation among the genomes. The putative list of SNPs that discriminate between disease-associated and carriage genomes may be expected to change with increased sampling or changes in the identities of the isolates being compared. Nevertheless, we show that these discriminating SNPs are more likely to reflect phenotypic differences than shared evolutionary history. Discriminating SNPs were mapped to genes, and the functions of the genes were evaluated for possible connections to virulence mechanisms. A number of overrepresented functional categories related to virulence were uncovered among SNP-associated genes, including genes related to the category "symbiosis, encompassing mutualism through parasitism."

Genomic Basis of a Polyagglutinating Isolate of Neisseria meningitidis

“…The total length of the genome was found to be 2,158,678 bp, and there were 2,337 predicted protein-coding genes. These results are consistent with a number of previous N. meningitidis genome sequence projects (16,17). Origin of the M16917 genome.…”

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

“…No clustering by disease phenotype was evident, with Clusters 1 and 2 containing both disease and carried isolates in similar proportions, indicating that the invasive and carried isolates circulating during the epidemic were part of the same bacterial population. This was consistent with previous genomic comparisons among more diverse carried and disease isolates, which found no distinct monophyletic groups by gene content [ 4 ] or SNP analysis [ 22 , 27 ].…”

Emergence of a New Epidemic Neisseria meningitidis Serogroup A Clone in the African Meningitis Belt: High-Resolution Picture of Genomic Changes That Mediate Immune Evasion

“…Translocation across the blood-brain barrier may in turn lead to the development of meningitis and/or septicemia. Here, we observed no common genomic differences, such as point mutations in particular loci ( 44 ), between colonization and disease isolates. This indicates that phenotypic changes rather than the expansion of genetic variants in the bloodstream play a key role in the switch from asymptomatic colonization to invasive disease.…”