Distribution of the type III DNA methyltransferases modA, modB and modD among Neisseria meningitidis genotypes: implications for gene regulation and virulence

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Author(s)
Tan, Aimee
Hill, Dorothea MC
Harrison, Odile B
Srikhanta, Yogitha N
Jennings, Michael P
Maiden, Martin CJ
Seib, Kate L
Year published
2016
Metadata
Show full item recordAbstract
Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci
are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive
meningococcal disease; however, those belonging to the ‘hyperinvasive lineages’ are more frequently
associated with sepsis or meningitis. Genome content is highly conserved between carriage and
disease isolates, and differential gene expression has been proposed as a major determinant of the
hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD),
which mediate epigenetic regulation of ...
View more >Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the ‘hyperinvasive lineages’ are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.
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View more >Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the ‘hyperinvasive lineages’ are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.
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Journal Title
Scientific Reports
Volume
6
Copyright Statement
© The Author(s). 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
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license, visit http://creativecommons.org/licenses/by/4.0/
Subject
Microbial Genetics